453 Polymorphism of Pro12Ala in the Peroxisome Proliferator-Activated Receptor γ2 Gene in Iranian Diabetic and Obese Subjects Hassan Mirzaei, M.Sc., 1,2 Seyed Mohammad Akrami, M.D., Ph.D., 3,4 Taghi Golmohammadi, Ph.D., 2 Mahmood Doosti, Ph.D., 2 Ramin Heshmat, M.D., Ph.D., 3 Manouchehr Nakhjavani, M.D., 5 and Parvin Amiri, M.Sc., 3 Abstract Background: Peroxisome proliferator-activated receptor γ2 (PPARγ2) is a nuclear receptor that regulates adipo- cyte differentiation, lipid metabolism, and insulin sensitivity. The aim of this study was to investigate the asso- ciation between the Pro12Ala single nucleotide polymorphism (SNP) at the PPARγ2 gene and type II diabetes (T2DM) and obesity in an Iranian population. Methods: The genomic DNA of the 312 subjects included four groups: (1) nonobese with type II diabetes, (2) obese without type II diabetes, (3) obese with type II diabetes, and (4) nondiabetic nonobese controls. The Pro12Ala polymorphism was detected by polymerase chain reaction–restriction fragment length polymorphism (PCR- RFLP) analysis. Results: Frequencies of the Ala allele in obese subjects were signifcantly different from those control subjects (odds ratio [OR], 2.358; 95% confdence interval [CI], 1.101–5.05) ( P =0.025). In contrast, no signifcant association was detected between the Pro12Ala polymorphism and type II diabetes (OR, 0.652; 95% CI, 0.261–1.628). In all subjects, the Ala carriers had a higher body mass index (BMI) compared with the common allele. Conclusions: Our results showed that the Pro12Ala polymorphism in the PPARγ2 gene is associated with obe- sity in Iranian subjects and the presence of the Ala allele could predict higher BMI. Introduction O besity is caused by an imbalance between energy intake and expenditure, resulting in weight gain. 1 The peroxisome proliferator activated receptor γ2 (PPARγ2) is an important transcription factor for lipid and glucose metab- olism that belongs to the same family of nuclear receptors as steroid and thyroid hormone receptors, 2,3 which have an essential role in adipogenesis and adipocyte gene expres- sion. PPARγ 1 and PPARγ2 are two isoforms arising from the PPARγ gene via differential promoter usage and alternative splicing. Human PPARγ2 has 28 additional amino acids at its amino terminus compared to PPARγ 1 and is expressed almost exclusively in adipose tissues, whereas PPARγ 1 is expressed in various tissues. 2–4 Obesity may be associated with elevated PPAR γ expres- sion. PPAR γ mRNA levels in white adipose tissue are unaf- fected in two murine models of obesity (gold thioglucose and ob/ob), but are increased up to 50% after high fat feeding in normal mice. 5 PPAR γ has an important role in adipocyte dif- ferentiation and regulates expression of key enzymes in lipid metabolism (eg, lipoprotein lipase, fatty acid binding transfer proteins, and hormone-sensitive lipase) as well as insulin sen- sitivity. 3 Recently, the single nucleotide polymophism (SNP) CCA→GCA in codon 12 of exon B of the PPAR γ2 gene was described in humans that resulted in the substitution of pro- line by alanine. 6 The aim of this study was to examine the asso- ciation between mutation of Pro12Ala of the PPARγ2 gene and type II diabetes (T2DM) or obesity in an Iranian population. 1 Department of Hygiene, Golestan University of Medical Sciences, Gorgan, Iran. 2 Department of Clinical Biochemistry, School of Medicine, 3 Endocrinology and Metabolism Research Center, 4 Medical Genetics Department, and 5 Endocrinology and Metabolism Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran. METABOLIC SYNDROME AND RELATED DISORDERS Volume 7, Number 5, 2009 © Mary Ann Liebert, Inc. Pp. 453–458 DOI: 10.1089/met.2008.0099 ORIGINAL ARTICLE CORE Metadata, citation and similar papers at core.ac.uk Provided by Golestan University of Medical Sciences Repository