|Year : 2019 | Volume
| Issue : 3 | Page : 192-200
|Peroxisome proliferator-activated receptor-γ gene polymorphism in psoriasis and its relation to obesity, metabolic syndrome, and narrowband ultraviolet B response: A case–control study in Egyptian patients
Iman Seleit1, Ola Ahmed Bakry1, Eman Abd El Gayed2, Mai Ghanem1
1 Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menoufiya University, Shibeen El Koom, Egypt
2 Department of Medical Biochemistry, Faculty of Medicine, Menoufiya University, Shibeen El Koom, Egypt
|Date of Web Publication||20-May-2019|
Dr. Ola Ahmed Bakry
Department of Dermatology, Andrology and STDs, Menoufiya Faculty of Medicine, Shibeen El Koom, 32817 Menoufiya Governorate
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Psoriasis is a common dermatologic disease with multifactorial etiology in which genetic factors play a major role. Peroxisome proliferator-activated receptor (PPAR)-γ is expressed in keratinocytes and is known to affect cell maturation and differentiation in addition to its role in inflammation. Aim: To study the association between PPAR-γ gene polymorphism and psoriasis vulgaris in Egyptian patients to explore if this polymorphism influenced disease risk or clinical presentation. Methods: Forty-five patients with psoriasis vulgaris and 45 age, sex and body mass index matched healthy volunteers who have no present, past or family history of psoriasis as a control group were enrolled. Selected cases included obese and nonobese participants. Detection of PPAR-γ gene polymorphism was done with restriction fragment length polymorphism polymerase chain reaction. Narrow-band ultraviolet B (NBUVB) was given for every case three times/week for 12 weeks. Results: Homopolymorphism, heteropolymorphism, and Ala allele were significantly associated with cases (P = 0.01, P = 0.01, and P = 0.004, respectively) and increased risk of occurrence of psoriasis by 5.25, 3.65, and 3.37 folds, respectively. Heteropolymorphism was significantly associated with nonobese cases compared to obese ones (P = 0.01). Ala allele was significantly associated with obese cases (P = 0.001) and increased risk of occurrence of psoriasis in obese participants by 1.14 folds. Homopolymorphism, heteropolymorphism, and Ala allele were more prevalent among obese cases without metabolic syndrome (MS) than obese cases with MS but without statistical significance. Percentage of decrease of mean Psoriasis Area and Severity Index score before and after 3 months of treatment with NBUVB was higher in cases with heteropolymorphism with no significant difference between homo- and heteropolymorphism. Conclusion: PPAR-γ gene polymorphism is associated with and increased the risk of psoriasis and its associated obesity in Egyptian patients. It has no role in NBUVB response in those patients. Future large-scale studies on different populations are recommended.
Keywords: Gene polymorphism, metabolic syndrome, obesity, peroxisome proliferator-activated receptor-γ, psoriasis
|How to cite this article:|
Seleit I, Bakry OA, Abd El Gayed E, Ghanem M. Peroxisome proliferator-activated receptor-γ gene polymorphism in psoriasis and its relation to obesity, metabolic syndrome, and narrowband ultraviolet B response: A case–control study in Egyptian patients. Indian J Dermatol 2019;64:192-200
|How to cite this URL:|
Seleit I, Bakry OA, Abd El Gayed E, Ghanem M. Peroxisome proliferator-activated receptor-γ gene polymorphism in psoriasis and its relation to obesity, metabolic syndrome, and narrowband ultraviolet B response: A case–control study in Egyptian patients. Indian J Dermatol [serial online] 2019 [cited 2019 Sep 22];64:192-200. Available from: http://www.e-ijd.org/text.asp?2019/64/3/192/258614
| Introduction|| |
Psoriasis is a common erythrosquamous skin disorder with varying clinical presentations. Psoriasis is a common dermatologic disease that affects >125 million people worldwide and its incidence seems to be increasing over time. The prevalence of psoriasis in Egypt ranges between 0.19% and 3%.
The exact disease pathogenesis is not yet settled, but most reports postulate that disease develops as a result of interaction between metabolic, environmental, and genetic factors.
Genetic factors play a fundamental role in the etiopathogenesis of psoriasis. There is evidence for at least eight psoriasis susceptibility loci, termed PSORS1-7 and PSORS9.
Obesity and metabolic syndrome (MS) are among the most important comorbidities of psoriasis.,, This may be due to lifestyle factors, shared inflammatory pathways, and genetic factors.
Peroxisome proliferator-activated receptors (PPARs): PPAR-α, PPAR-β/δ, and PPAR-γ, are nuclear hormone receptors that act as key transcriptional regulators of lipid and glucose metabolism. In addition, they have been shown to regulate cell proliferation and differentiation, tumor promotion, apoptosis, and immune reactions.
PPAR-γ acts against psoriasis development by several ways. Psoriasis is Th-1 inflammatory disease such as obesity, MS, diabetes, atherosclerosis, and myocardial infarction. PPAR-γ activation requires the presence of a Th2 cytokine profile and downregulation of Th-1 response. Thereby, PPAR-γ acts as anti-inflammatory combating against psoriasis and its comorbidities. It also suppresses interleukin (IL)-17 gene transcription, inhibits vascular endothelial growth factor with subsequent inhibition of angiogenesis required for psoriasis development, inhibits nuclear factor-kβ and activating protein, signal transducer and activator of transcription, IL-2 production as well as tumor necrosis factor-α by T-lymphocytes. PPAR-γ enhances the production of adiponectin which was proved to be deficient in psoriasis. It also protects against oxidative stress and induces apoptosis and death of immune cells, especially T-lymphocytes.
Therefore, reduced PPAR-γ activity leads to subsequent severe psoriasis and high susceptibility to its comorbidities.
In skin, PPAR-γ is expressed in suprabasal keratinocytes, hair follicles, and sebaceous glands. It was found to induce keratinocyte maturation, inhibit proliferation, induce apoptosis and modulate filaggrin expression.
The gene encoding for PPAR-γ is located on chromosome 3p25.2, contains 9 exons and spans more than 100 kb.
A polymorphism is a genetic variant that appears in at least 1% of the population. A gene is said to be polymorphic if more than one allele occupies that gene's locus within a population. Sources of gene polymorphism include single-nucleotide polymorphisms, sequence repeats, insertions, deletions and recombination. It may result from chance processes or may have been induced by external agents such as viruses or radiation.
Accumulating evidence indicated that both common and rare polymorphisms of PPAR-γ gene play key roles in the regulation of lipid and glucose metabolism. Genetic variants in the PPAR-γ gene have been reported to be associated with obesity and with severe insulin resistance.
Although PPAR-γ locus is distant from currently accepted psoriasis susceptibility loci, this does not exclude the possibility that it may have effects on certain aspects of the disease.
The most prevalent PPAR-γ polymorphism is a variant that replaces alanine with proline at codon 12 (Pro12Ala). When both alleles are replaced, this is called homopolymorphism (Ala/Ala). When only one allele is replaced, this is called heteropolymorphism (Pro/Ala). Pro12Ala polymorphism has been associated with reduced transcriptional and receptor activity of PPAR-γ.
Based on the putative role of PPAR-γ in the maintenance of skin homeostasis, and in inflammatory processes, we speculated that genetically determined alterations in its functional activity may contribute to the pathogenesis of psoriasis. Therefore, we aimed at investigating PPAR-γ Pro12Ala polymorphism in Egyptian psoriatic cases searching for its role in disease occurrence and increased disease risk.
| Methods|| |
This case–control study was conducted on 45 patients with psoriasis vulgaris and 45 age, sex, and body mass index (BMI)-matched healthy volunteers, who have no present, past, or family history of psoriasis, as a control group.
Cases were selected from the dermatology outpatient clinic during the period from June 2016 to December 2016. Control participants were selected from the healthy staff of Menoufiya University Hospital. Laboratory part of the study was done at the Biochemistry Department at Menoufiya Faculty of Medicine.
Written consent form approved by the Local Ethical Research Committee was obtained from every participant before the study initiation. This was in accordance with the Helsinki Declaration of 1975 (revised in 2000).
Cases were either newly diagnosed with no history of treatment or stopped treatment for at least 3 months before sample taking.
Clinical data describing patients' demographics (age and gender) as well as the clinical variables (site of lesion[s], age of onset, disease duration, nail involvement, joint involvement, mucosal affection, itching, Koebnerization, and family history of psoriasis) were all documented.
The severity of the disease was assessed by Psoriasis Area and Severity Index (PASI) score.
Narrow-band (312 nm) ultraviolet B treatment
It was scheduled as follows for every case:
- The starting dose – the initial radiation dose was determined according to the patient's skin type. Included cases had skin Types III or IV and were initially treated with 0.5 mJ/cm2
- Dose increments – dose increment was done every session according to the degree of erythema as follows: if no erythema, dose increment was 20%; if minimal erythema, dose increment was 10%; and if intense erythema or erythema and edema or erythema, edema and blisters, no dose increment was done
- Dose frequency – sessions were given three times weekly for 12 weeks
- The machine used – ultraviolet (UV)-100 L Waldman (Germany) lighting, equipped with UVB lamps (TL01 lamp), which have physical irradiance values of 7–10 mW/cm2 and biological effective (erythematous) irradiance of 0.4–0.6 mW/cm2
- Assessment – percentage of decrease in the mean PASI score after the treatment period.
Any case or control participant with dermatological diseases other than psoriasis, polycystic ovarian syndrome, coronary artery disease, breast cancer, and/or blood transfusion in the last 6 months was excluded from the study.
Every case and control participant underwent the following steps
- Determination of BMI. Selected cases and controls included obese and nonobese participants
- Evaluation for the presence of MS whose criteria were identified according to the National Cholesterol Education Program Adult Treatment Panel III
- Detection of PPAR-γ gene polymorphism by restriction fragment length polymorphism polymerase chain reaction (PCR).
DNA extraction from the whole blood was done using the GeneJET whole blood genomic DNA purification Mini Kit (Thermo Scientific Lithuania). DNA eluted in buffer AE was stored at −20°C for further PCR procedure.
Determination of peroxisome proliferator-activated receptor-γ gene polymorphism
PCR for PPAR-γ gene polymorphism was carried out to a total volume of 25 μl, containing 10 μl genomic DNA, 1 μl of each primer, 12.5 μl of Master Mix (Genecraft, Germany and Stratagene, USA), and 1.5 μl distilled water.
Peroxisome proliferator-activated receptor-γ gene
It was analyzed using the following designed primers (Midland, Texas)
Polymerase chain reaction amplification of peroxisome proliferator-activated receptor-γ gene
It was done using Applied Biosystems 2720 thermal cycler (Singapore). PCR condition consisted of one cycle of amplification at 94°C for 3 min, followed by 30 cycles at 94°C for 1 min, 55°C for 1 min, 72°C for 1 min, and one final cycle of extension at 72°C for 10 min. The amplification products were separated by electrophoresis through 3% agarose gel stained with ethidium bromide and visualized with positive band at 244 bp.
Peroxisome proliferator-activated receptor-γ genotyping using restriction fragment length polymorphism polymerase chain reaction technique
About 15 μl of the PCR products of PPAR-γ gene was mixed with 1 μl (1 unit) of FastDigest® BstUI restriction enzyme (provided by Fermentas) with 6.5 μl nuclease-free water and 2.5 μl of 10X FastDigest® Buffer.
The mixture was mixed well and incubated at 60°C for 30 min, then 10 μl of the product was loaded into a 3% agarose gel containing ethidium bromide for electrophoresis. The uncut fragment was 244 bp and digestion products were 223 bp and 21 bp.
Data were collected, tabulated and statistically analyzed using a personal computer with SPSS version 11 program (SPSS Inc., Chicago, IL, USA). Fisher's exact test was used for comparison of qualitative variables in 2 × 2 tables when expected cell count of more than 25% of cases was <5. Chi-square test (χ2) was used to study the association between two qualitative normally distributed variables. Mann–Whitney U-test was used for comparison between two groups not normally distributed having quantitative variables. Odds ratio (OR) was used to describe the probability that people who are exposed to a certain factor will have a disease compared to people who are not exposed to the factor. Differences were considered statistically significant with P < 0.05.
| Results|| |
Selected cases included 25 nonobese and 20 obese participants. Among obese cases, 6 participants fulfilled the criteria of MS and 14 had no MS. Clinical data of patients are shown in [Table 1].
Prevalence of peroxisome proliferator-activated receptor-γ genotypes and alleles in studied groups
Cases and controls
Homopolymorphism (Ala/Ala genotype) was significantly associated with cases (P = 0.01), and it increased risk of occurrence of psoriasis by 5.25 folds. Heteropolymorphism (Pro/Ala genotype) was more prevalent in cases (P = 0.01), and it increased risk of occurrence of psoriasis by 3.65 folds [Figure 1]a.
|Figure 1: (a) The prevalence of peroxisome proliferator-activated receptor-γ genotypes in cases and control participants. (b) The prevalence of peroxisome proliferator-activated receptor-γ alleles in cases and control participants. (c) Significant association between heteropolymorphism and nonobese cases. (d) Significant association between Ala allele and obese cases. (e) Significant association between heteropolymorphism and nonobese cases. (f) Significant association between Ala allele and nonobese cases|
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Ala allele was significantly associated with cases (P = 0.004). It increased risk of occurrence of psoriasis by 3.37 folds [Figure 1]b.
Nonobese and obese cases
Homopolymorphism was present only in obese cases (P = 0.01). Heteropolymorphism was significantly associated with nonobese cases (P = 0.01) with OR of 3.65 [Figure 1]c. Ala allele was significantly associated with obese cases (P = 0.001) and increased risk of occurrence of psoriasis in obese participants by 1.14 folds [Figure 1]d.
Nonobese cases and nonobese controls
Heteropolymorphism was significantly associated with nonobese cases (P = 0.001), and it increased risk of occurrence of psoriasis by 12 folds [Figure 1]e. Ala allele was significantly associated with nonobese cases (P = 0.006). It increased risk of occurrence of psoriasis by 3.76 folds [Figure 1]f.
Obese cases and obese controls
Normal genotype has equal prevalence among obese controls and obese cases (2%). Homopolymorphism was more prevalent among obese cases (60% vs. 25%), and heteropolymorphism was more prevalent among obese controls (62% vs. 30%) but without significant difference between both groups (data not shown in tables or figures).
Ala allele was more prevalent among obese controls (57.5% vs. 38%), and Pro allele was more prevalent among obese cases (62% vs. 42.5%) without significant difference between both groups (data not shown in tables or figures).
Obese cases with and without metabolic syndrome
Homopolymorphism and heteropolymorphism were more prevalent among obese cases without MS than obese cases with MS (64.3% vs. 50% and 35.7% vs. 16.7%, respectively) but without significant difference between the groups (data not shown in tables or figures).
Ala allele was more prevalent among obese cases without MS (82.1% vs. 38%), and Pro allele was more prevalent among obese cases with MS (62% vs. 17.9%) with no significant difference between both groups (data not shown in tables or figures).
Relationship between peroxisome proliferator-activated receptor-γ genotypes and clinical data of selected cases
Homopolymorphism and Ala allele were significantly associated with higher BMI (P = 0.001 for both) [Figure 2]a and [Figure 2]b.
|Figure 2: Significant association between (a) homopolymorphism and higher body mass index and (b) Ala allele and higher body mass index|
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Relationship between genotypes and narrow-band ultraviolet B response in selected cases
Percentage of decrease of mean PASI score before and after 3 months of treatment with narrowband ultraviolet B (NBUVB) was higher in cases with heterolymorphism with no significant difference between homo- and heteropolymorphism [Table 2].
|Table 2: Relationship between peroxisome proliferator-activated receptor genotypes and narrowband ultraviolet B response in studied cases|
Click here to view
| Discussion|| |
The current study showed significant difference between psoriatic cases and healthy controls, regarding PPAR-γ Pro12Ala gene polymorphism. Homopolymorphism (Ala/Ala) and heteropolymorphism (Pro/Ala) were associated with psoraitic patients and increased risk of occurrence of psoriasis by 5.25 and 3.65 folds, respectively.
This conflicted with Mossner et al. who reported no association between PPAR-γ polymorphisms and uncomplicated psoriasis. These different findings could be explained by different clinical criteria, and ethnic background of studied populations as a single genetic mutation may result in conflict outcomes in different ethnic groups.
As mentioned earlier, PPAR-γ can affect keratinocyte maturation and inflammatory mediators, inhibit proliferation, and induce apoptosis. As PPAR-γ gene polymorphism will decrease its transcriptional activity, the association demonstrated here may be explained by loss of PPAR-γ biological effects on keratinocytes, angiogenesis, inflammatory mediators, and immune cells; a postulation that needs further research.
In the current work, Ala allele was significantly associated with obese cases compared with nonobese ones and increased risk of occurrence of psoriasis in obese patients by 1.14 folds.
The association between Ala12 and high BMI is a matter of debate. While some studies confirmed it,,,, others denied such association.,,,,,,,
PPAR-γ is proadipogenic. The decreased transactivation function by polymorphism will lead to decreased lipoprotein lipase activity and decreased plasma free fatty acids which adversely affect insulin action on skeletal muscles.
In addition, activators of PPAR-γ have been shown to promote differentiation of preadipocytes to small adipocytes. In small adipocytes, lipolysis is more insulin sensitive than in large adipocytes (insulin action is already impaired by the polymorphism as mentioned above).
In humans, PPAR-γ expression in visceral adipose tissue relative to subcutaneous adipose tissue is increased in obese participants. Because visceral adipose tissue is metabolically more harmful, the Ala allele would be expected to have an even greater impact in obese participants.
Lifestyle changes and weight reduction lead to improvement or complete remission of psoriasis. However, based on the current results, these measures may go side by side with genetic interference in cases of polymorphism.
In the present study, homopolymorphism and heteropolymorphism were more prevalent among cases without MS than cases with MS.
Several studies identified a higher prevalence of MS in psoriatic patients compared to nonpsoriatic controls., PPAR-γ activity protects against components of MS. PPAR-γ agonists have been reported to reduce blood pressure in human diabetic participants and in animal models, and loss of functional mutations in PPAR-γ leads to severe early-onset hypertension in addition to metabolic abnormalities. Furthermore, PPAR-γ is associated with improved insulin sensitivity, lower BMI, increased high-density lipoprotein (HDL) levels, and a reduced risk of developing type 2 diabetes mellitus.
The functional Pro12Ala mutation has also been reported to be associated with MS in several reports as this polymorphism can modulate the association between dietary fat intake and components of the MS.,
It was previously reported that reduction in the PPAR-γ expression goes hand in hand with elevation of the PASI score, blood glucose, blood pressure and cholesterol levels as well as reduction of the HDL levels (components of the MS), pointing to the common influence induced by reduced PPAR-γ levels on both psoriasis and MS.
However, some studies found no association between Pro12Ala polymorphism of PPAR-γ and MS.,
Zhang et al. reported that epidermal PPAR-γ signaling is also a target for UV-induced inflammatory response. UV irradiation of human keratinocytes produces potent PPAR-γ agonistic activity in these cells. Hence, we studied the relationship between PPAR-γ gene polymorphism and the response of NBUVB in psoriatic patients.
Unexpectedly, no association was detected between NBUVB response and PPAR-γ genotypes or alleles. Large-scale studies are needed to confirm or deny such finding.
Studying the relationship between genetic background of psoriatic patients and their response to phototherapy is needed as it may decrease refractory cases and improve treatment outcome.
| Conclusion|| |
PPAR-γ gene polymorphism is associated with and increases the risk of psoriasis in Egyptian patients. However, it has no role in NBUVB response in those patients.
Future large-scale studies on different populations are needed for firmer conclusion. Investigating gene polymorphism in other clinical varieties of psoriasis and investigating the association between psoriasis and other PPAR-γ polymorphisms are also needed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Parisi R, Symmons DP, Griffiths CE, Ashcroft DM; Identification and Management of Psoriasis and Associated Comorbidity (IMPACT) Project Team. Global epidemiology of psoriasis: A systematic review of incidence and prevalence. J Invest Dermatol 2013;133:377-85.
Omar SS, Helaly HA. Prevalence of ocular findings in a sample of Egyptian patients with psoriasis. Indian J Dermatol Venereol Leprol 2018;84:34-8.
] [Full text]
Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, et al.
Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 2008;58:826-50.
Henseler T. Genetics of psoriasis. Arch Dermatol Res 1998;290:463-76.
Thappa DM, Gupta D. Prevalence of metabolic syndrome in South Indian patients with psoriasis vulgaris and the relation between disease severity and metabolic syndrome: A hospital-based case-control study or cross-sectional study? Indian J Dermatol 2013;58:315.
] [Full text]
Kimball AB, Jacobson C, Weiss S, Vreeland MG, Wu Y. The psychosocial burden of psoriasis. Am J Clin Dermatol 2005;6:383-92.
Block JP, He Y, Zaslavsky AM, Ding L, Ayanian JZ. Psychosocial stress and change in weight among US adults. Am J Epidemiol 2009;170:181-92.
Gisondi P, Ferrazzi A, Girolomoni G. Metabolic comorbidities and psoriasis. Acta Dermatovenereol Croat 2010;18:297-304.
Michalik L, Wahli W. Peroxisome proliferator-activated receptors (PPARs) in skin health, repair and disease. Biochim Biophys Acta 2007;1771:991-8.
Sertznig P, Seifert M, Tilgen W, Reichrath J. Peroxisome proliferator-activated receptors (PPARs) and the human skin: Importance of PPARs in skin physiology and dermatologic diseases. Am J Clin Dermatol 2008;9:15-31.
Azfar RS, Gelfand JM. Psoriasis and metabolic disease: Epidemiology and pathophysiology. Curr Opin Rheumatol 2008;20:416-22.
Osella-Abate S, Zaccagna A, Savoia P, Quaglino P, Salomone B, Bernengo MG, et al.
Expression of apoptosis markers on peripheral blood lymphocytes from patients with cutaneous T-cell lymphoma during extracorporeal photochemotherapy. J Am Acad Dermatol 2001;44:40-7.
Jo SH, Yang C, Miao Q, Marzec M, Wasik MA, Lu P, et al.
Peroxisome proliferator-activated receptor gamma promotes lymphocyte survival through its actions on cellular metabolic activities. J Immunol 2006;177:3737-45.
Nakajima H, Nakajima K, Tarutani M, Morishige R, Sano S. Kinetics of circulating Th17 cytokines and adipokines in psoriasis patients. Arch Dermatol Res 2011;303:451-5.
Kim KY, Ahn JH, Cheon HG. Anti-angiogenic action of PPARγ ligand in human umbilical vein endothelial cells is mediated by PTEN upregulation and VEGFR-2 downregulation. Mol Cell Biochem 2011;358:375-85.
Yang XY, Wang LH, Chen T, Hodge DR, Resau JH, DaSilva L, et al.
Activation of human T lymphocytes is inhibited by peroxisome proliferator-activated receptor gamma (PPARgamma) agonists. PPAR gamma co-associated with transcription factor NFAT. J Biol Chem 2000;275:4541-4.
Tanaka T, Masuzaki H, Hosoda K, Nakao K. Critical roles of PPAR gamma in every aspect of the metabolic syndrome. Nihon Rinsho 2010;68:203-9.
Al Saleh A, Sanders TA, O'Dell SD. Effect of interaction between PPARG, PPARA and ADIPOQ gene variants and dietary fatty acids on plasma lipid profile and adiponectin concentration in a large intervention study. Proc Nutr Soc 2012;71:141-53.
Fuenzalida K, Quintanilla R, Ramos P, Piderit D, Fuentealba RA, Martinez G, et al.
Peroxisome proliferator-activated receptor gamma up-regulates the Bcl-2 anti-apoptotic protein in neurons and induces mitochondrial stabilization and protection against oxidative stress and apoptosis. J Biol Chem 2007;282:37006-15.
Schmidt MV, Brüne B, von Knethen A. The nuclear hormone receptor PPARγ as a therapeutic target in major diseases. ScientificWorldJournal 2010;10:2181-97.
Ramot Y, Mastrofrancesco A, Camera E, Desreumaux P, Paus R, Picardo M, et al.
The role of PPARγ-mediated signalling in skin biology and pathology: New targets and opportunities for clinical dermatology. Exp Dermatol 2015;24:245-51.
Westergaard M, Henningsen J, Svendsen ML, Johansen C, Jensen UB, Schrøder HD, et al.
Modulation of keratinocyte gene expression and differentiation by PPAR-selective ligands and tetradecylthioacetic acid. J Invest Dermatol 2001;116:702-12.
Mao-Qiang M, Fowler AJ, Schmuth M, Lau P, Chang S, Brown BE, et al.
Peroxisome-proliferator-activated receptor (PPAR)-gamma activation stimulates keratinocyte differentiation. J Invest Dermatol 2004;123:305-12.
Francis GA, Fayard E, Picard F, Auwerx J. Nuclear receptors and the control of metabolism. Annu Rev Physiol 2003;65:261-311.
Smith K. Genetic polymorphism and SNPs: Genotyping, haplotype assembly problem, haplotype map. Funct Genomic Proteomic 2002;3:1-9.
Zhao X, Xu K, Shi H, Cheng J, Ma J, Gao Y, et al.
Application of the back-error propagation artificial neural network (BPANN) on genetic variants in the PPAR-γ and RXR-α gene and risk of metabolic syndrome in a Chinese Han population. J Biomed Res 2014;28:114-22.
Ristow M, Müller-Wieland D, Pfeiffer A, Krone W, Kahn CR. Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N Engl J Med 1998;339:953-9.
Barroso I, Gurnell M, Crowley VE, Agostini M, Schwabe JW, Soos MA, et al.
Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 1999;402:880-3.
Traupe H. The complex genetics of psoriasis. In: Van de Kerkhof PC, editor. Textbook of Psoriasis. Oxford: Blackwell; 1999. p. 68-78.
Meirhaeghe A, Amouyel P. Impact of genetic variation of PPARgamma in humans. Mol Genet Metab 2004;83:93-102.
Louden BA, Pearce DJ, Lang W, Feldman SR. A simplified psoriasis area severity index (SPASI) for rating psoriasis severity in clinic patients. Dermatol Online J 2004;10:7.
Zanolli MD, Felmam SR, Clark AR, Naomi N. Psoriasis ultraviolet B, (UVB) phototherapy by skin type. In: Michael DZ, Steven RF, editors. Phototherapy Treatment Protocols. 1st
ed. New York, USA: The Parthenon Publishing Group; 2000. p. 8-12.
Garrow JS, Webster J. Quetelet's index (W/H2) as a measure of fatness. Int J Obes 1985;9:147-53.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult treatment panel III). JAMA 2001;285:2486-97.
Motavallian A, Andalib S, Vaseghi G, Mirmohammad-Sadeghi H, Amini M. Association between PRO12ALA polymorphism of the PPAR-γ2 gene and type 2 diabetes mellitus in Iranian patients. Indian J Hum Genet 2013;19:239-44.
] [Full text]
Mössner R, Kaiser R, Matern P, Krüger U, Westphal GA, Brockmöller J, et al.
Variations in the genes encoding the peroxisome proliferator-activated receptors alpha and gamma in psoriasis. Arch Dermatol Res 2004;296:1-5.
Delarue J, Magnan C. Free fatty acids and insulin resistance. Curr Opin Clin Nutr Metab Care 2007;10:142-8.
Deeb SS, Fajas L, Nemoto M, Pihlajamäki J, Mykkänen L, Kuusisto J, et al.
A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 1998;20:284-7.
Barbieri M, Rizzo MR, Papa M, Acampora R, De Angelis L, Olivieri F, et al.
Role of interaction between variants in the PPARG and interleukin-6 genes on obesity related metabolic risk factors. Exp Gerontol 2005;40:599-604.
Rosado EL, Bressan J, Martins MF, Cecon PR, Martínez JA. Polymorphism in the PPARgamma2 and beta2-adrenergic genes and diet lipid effects on body composition, energy expenditure and eating behavior of obese women. Appetite 2007;49:635-43.
Bouhaha R, Meyre D, Kamoun HA, Ennafaa H, Vaillant E, Sassi R, et al.
Effect of ENPP1/PC-1-K121Q and PPARgamma-pro12Ala polymorphisms on the genetic susceptibility to T2D in the Tunisian population. Diabetes Res Clin Pract 2008;81:278-83.
Ochoa MC, Marti A, Azcona C, Chueca M, Oyarzábal M, Pelach R, et al.
Gene-gene interaction between PPAR gamma 2 and ADR beta 3 increases obesity risk in children and adolescents. Int J Obes Relat Metab Disord 2004;28 Suppl 3:S37-41.
Kim KS, Choi SM, Shin SU, Yang HS, Yoon Y. Effects of peroxisome proliferator-activated receptor-gamma 2 Pro12Ala polymorphism on body fat distribution in female Korean subjects. Metabolism 2004;53:1538-43.
Danawati CW, Nagata M, Moriyama H, Hara K, Yasuda H, Nakayama M, et al
. A possible association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma2 gene with obesity in native Javanese in Indonesia. Diabetes Metab Res Rev 2005;21:465-9.
Meirhaeghe A, Tanck MW, Fajas L, Janot C, Helbecque N, Cottel D, et al
. Study of a new PPARgamma2 promoter polymorphism and haplotype analysis in a French population. Mol Genet Metab 2005;85:140-8.
Mattevi VS, Zembrzuski VM, Hutz MH. Effects of a PPARG gene variant on obesity characteristics in Brazil. Braz J Med Biol Res 2007;40:927-32.
Morini E, Tassi V, Capponi D, Ludovico O, Dallapiccola B, Trischitta V, et al.
Interaction between PPARgamma2 variants and gender on the modulation of body weight. Obesity (Silver Spring) 2008;16:1467-70.
Li LL, Ma XL, Ran JX, Sun XF, Xu LM, Ren J, et al.
Genetic polymorphism of peroxisome proliferator-activated receptor-gamma 2 Pro12Ala on ethnic susceptibility to diabetes in Uygur, Kazak and Han subjects. Clin Exp Pharmacol Physiol 2008;35:187-91.
Lagou V, Scott RA, Manios Y, Chen TL, Wang G, Grammatikaki E, et al
. Impact of peroxisome proliferator-activated receptors gamma and delta on adiposity in toddlers and preschoolers in the GENESIS study. Obesity (Silver Spring) 2008;16:913-8.
Schneider J, Kreuzer J, Hamann A, Nawroth PP, Dugi KA. The proline 12 alanine substitution in the peroxisome proliferator – Activated receptor-gamma2 gene is associated with lower lipoprotein lipase activity in vivo
. Diabetes 2002;51:867-70.
Stumvoll M, Häring H. Reduced lipolysis as possible cause for greater weight gain in subjects with the Pro12Ala polymorphism in PPARgamma2? Diabetologia 2002;45:152-3.
Stumvoll M, Wahl HG, Löblein K, Becker R, Machicao F, Jacob S, et al
. Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma2 gene is associated with increased antilipolytic insulin sensitivity. Diabetes 2001;50:876-81.
Okuno A, Tamemoto H, Tobe K, Ueki K, Mori Y, Iwamoto K, et al.
Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese zucker rats. J Clin Invest 1998;101:1354-61.
Abbott WG, Foley JE. Comparison of body composition, adipocyte size, and glucose and insulin concentrations in Pima Indian and Caucasian children. Metabolism 1987;36:576-9.
Adams M, Montague CT, Prins JB, Holder JC, Smith SA, Sanders L, et al.
Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation. J Clin Invest 1997;100:3149-53.
Aune D, Snekvik I, Schlesinger S, Norat T, Riboli E, Vatten LJ, et al.
Body mass index, abdominal fatness, weight gain and the risk of psoriasis: A systematic review and dose-response meta-analysis of prospective studies. Eur J Epidemiol 2018. [Ahead of print].
Lefebvre AM, Laville M, Vega N, Riou JP, van Gaal L, Auwerx J, et al.
Depot-specific differences in adipose tissue gene expression in lean and obese subjects. Diabetes 1998;47:98-103.
Montague CT, O'Rahilly S. The perils of portliness: Causes and consequences of visceral adiposity. Diabetes 2000;49:883-8.
Koch M, Rett K, Maerker E, Volk A, Haist K, Deninger M, et al.
The PPARgamma2 amino acid polymorphism pro 12 Ala is prevalent in offspring of type II diabetic patients and is associated to increased insulin sensitivity in a subgroup of obese subjects. Diabetologia 1999;42:758-62.
Cohen AD, Sherf M, Vidavsky L, Vardy DA, Shapiro J, Meyerovitch J, et al.
Association between psoriasis and the metabolic syndrome. A cross-sectional study. Dermatology 2008;216:152-5.
Sommer DM, Jenisch S, Suchan M, Christophers E, Weichenthal M. Increased prevalence of the metabolic syndrome in patients with moderate to severe psoriasis. Arch Dermatol Res 2006;298:321-8.
Agostini M, Schoenmakers E, Mitchell C, Szatmari I, Savage D, Smith A, et al.
Non-DNA binding, dominant-negative, human PPARgamma mutations cause lipodystrophic insulin resistance. Cell Metab 2006;4:303-11.
Mori H, Ikegami H, Kawaguchi Y, Seino S, Yokoi N, Takeda J, et al
. The Pro12Ala substitution in PPAR-gamma is associated with resistance to development of diabetes in the general population: Possible involvement in impairment of insulin secretion in individuals with type 2 diabetes. Diabetes 2001;50:891-4.
Tellechea ML, Aranguren F, Pérez MS, Cerrone GE, Frechtel GD, Taverna MJ, et al
. Pro12Ala polymorphism of the peroxisome proliferatoractivated receptor-gamma gene is associated with metabolic syndrome and surrogate measures of insulin resistance in healthy men: Interaction with smoking status. Circ J 2009;73:2118-24.
Robitaille J, Després JP, Pérusse L, Vohl MC. The PPAR-gamma P12A polymorphism modulates the relationship between dietary fat intake and components of the metabolic syndrome: Results from the Québec Family Study. Clin Genet 2003;63:109-16.
Hegazy RA, Abdel Hay RM, Shaker O, Sayed SS, Abdel Halim DA. Psoriasis and metabolic syndrome: Is peroxisome proliferator-activated receptor-γ part of the missing link? Eur J Dermatol 2012;22:622-8.
Yang LL, Hua Q, Liu RK, Yang Z. Association between two common polymorphisms of PPARgamma gene and metabolic syndrome families in a Chinese population. Arch Med Res 2009;40:89-96.
Zhang Q, Southall MD, Mezsick SM, Johnson C, Murphy RC, Konger RL, et al.
Epidermal peroxisome proliferator-activated receptor gamma as a target for ultraviolet B radiation. J Biol Chem 2005;280:73-9.
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