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  • Title: Genetic variants in peroxisome proliferator-activated receptor-γ and retinoid X receptor-α gene and type 2 diabetes risk: a case-control study of a Chinese Han population.
    Author: Lu Y, Ye X, Cao Y, Li Q, Yu X, Cheng J, Gao Y, Ma J, Du W, Zhou L.
    Journal: Diabetes Technol Ther; 2011 Feb; 13(2):157-64. PubMed ID: 21284483.
    Abstract:
    BACKGROUND: The serum levels of adiponectin are paradoxically decreased in obesity and may play important roles in the development of type 2 diabetes mellitus (T2DM). Potentially functional polymorphisms in the peroxisome proliferator-activated receptor-γ (PPAR-γ) and retinoid X receptor-α (RXR-α) genes may alter T2DM risks by increasing the human adiponectin promoter activity in cells. Therefore, we hypothesized that single nucleotide polymorphisms (SNPs) in PPAR-γ and RXR-α were associated with risk of T2DM. To test this hypothesis, three potentially functional SNPs of PPAR-γ and four of RXR-α with a minor allele frequency of ≥ 0.05 in the Chinese Han population were identified from the National Center for Biotechnology Information dbSNPs database to evaluate their association with T2DM. METHODS: Polymerase chain reaction-restriction fragment length polymorphism was performed to test the genotypes in T2DM patients (n = 540) and normal controls (n = 604). RESULTS: The variant genotypes rs2920502CC, rs3856806CT, rs3856806CT/TT, and rs4240711AG/GG were associated with T2DM. Furthermore, the prevalences of haplotype GTC and CTG in PPAR-γ and GTAC in RXR-α were less frequent in cases (17.1%, 2.6%, and 2.4%, respectively) than in controls (22.3%, 3.8%, and 6.6%, respectively), whereas GTGT in RXR-α was more frequent in cases (6.9%) than in controls (4.4%) (P < 0.05 for both two-sided χ(2) test and thousand times permutation tests). Patients with genotype CT/TT of rs3856806 and genotype AG/GG of rs4240711 had higher levels of serum adiponectin than those with the genotype CC and genotype AA (P = 0.026 and 0.021, respectively). Model X2 X5 X6 X7 (rs3856806, rs3132291, rs4240711, and rs4842194) was the best model with the highest test balanced accuracy (0.5764) (cross-validation consistency = 10/10) in the multifactor dimensionality reduction method. CONCLUSIONS: The PPAR-γ and RXR-α gene variants associated with the development of T2DM in this study must be investigated in a larger population to reveal any potential effects on metabolism.
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