
EFFECT OF THE Pro12Ala POLYMORPHISM OF THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR γ2 GENE ON LIPID PROFILE AND ADIPOKINES LEVELS IN OBESE SUBJECTS
Becer E1,2,*, Çırakoğlu A3
*Corresponding Author: Eda Becer, Ph.D., M.Sc., Department of Biochemistry, Faculty of Pharmacy, Near East University, Nicosia, Mersin 10, Turkey. Tel: +90-392-680-2000, Ext: 128. Fax:+90-392-680-2038. E-mail: edabecer@yahoo.com
page: 71
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INTRODUCTION
The proxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear hormone receptor superfamily and plays an important role in energy storage, adipocyte differentiation, insulin sensitization and fatty acid metabolism [1]. The PPARγ1, PPARγ2 and PPARγ3 are generated by separate promoters and 5’ exons. Separate promoters and 5’ exons generate three mRNA isoforms: PPARγ1, PPARγ2 and PPARγ3. The PPARγ1 and PPARγ3 mRNAs encode the same protein products, whereas PPARγ2 protein contains an additional NH2-terminal region composed of 30 amino acids. The PPARγ1 gene is expressed in nearly all cells, while PPARγ2 expression is limited mainly to adipose tissue [2]. Both PPARγ1 and PPARγ2 isoforms are an important adipogenic regulator and essential for the control of insulin sensitivity. However, PPARγ2 regulates response to nutrient intake and obesity. These characteristic properties make it a key molecule to be involved in the expression of adipokines such as leptin, adiponectin, resistin and chemerin, which may act as modulators of energy metabolism and insulin action [3]. Moreover, PPARγ2 mediates the expression of specific fat tissue cell genes that also participates in lipogenic pathways and adipocyte hypertrophy [4]. The PPARγ2 gene is located on chromosome 3p25 [5]. Several single nucleotide polymorphisms (SNPs) of the PPARγ2 gene have been identified and one of these poly-morphisms is Pro12Ala (rs1801282). The Pro12Ala polymorphism results from a cytosine to guanine substitution at nucleotide 34 of exon B and leads to a proline to alanine at position 12 of the PPARγ2 protein [6]. The alanine allele was shown to have reduced affinity for response element and lower capacity for activating target genes [7]. In recent years, several studies have focused on the association between the Pro12Ala polymorphism and complex traits such as obesity, type 2 diabetes mellitus (T2DM) and insulin sensitivity, have been reported [8,9]. Many studies have indicate that the alanine allele decreased risk of T2DM and increased insulin sensitivity [10,11]. However, studies on an association between the Pro12Ala polymorphism and obesity-related metabolic diseases have yielded inconsistent results [8,12,13]. The mechanisms underlying the association of obesity and insulin sensitivity mainly involve altering the production of hormones and molecules related to adipose tissue and energy metabolism, such as leptin, adiponectin, resistin and chemerin. Therefore, the impact of the Pro12Ala polymorphism of the PPARγ2 gene on regulating adipokines expression will provide a better appreciation of the pathogenic mechanisms underlying obesity and associated comorbidities. However, the available data are still limited and conflicting. Thus, the aim of this study was to investigate the associations between the PPARγ2 gene Pro12Ala polymorphism, body mass index (BMI), lipid parameters, homeostasis model assessment of insulin resistance (HOMA-IR), serum leptin, adiponectin, resistin and chemerin levels in obese subjects versus non obese subjects.
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