Single nucleotide polymorphisms of PPARD in combination with the Gly482Ser substitution of PGC-1A and the Pro12Ala substitution of PPARG2 predict the conversion from impaired glucose tolerance to type 2 diabetes -: The STOP-NIDDM trial

被引:54
作者
Andrulionyte, Laura
Peltola, Paula
Chiasson, Jean-Louis
Laakso, Markku [1 ]
机构
[1] Univ Kuopio, Dept Med, Kuopio 70210, Finland
[2] Univ Montreal, Ctr Hosp, Hotel Dieu, Res Ctr,Dept Med, Montreal, PQ H3C 3J7, Canada
关键词
D O I
10.2337/db05-1629
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Peroxisome proliferator-activated receptor (PPAR)-delta regulates fatty acid oxidation and improves insulin sensitivity. We screened six single nucleotide polymorphisms (SNPs) of the PPAR-delta gene (PPARD) for an association with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in 769 subjects participating in the STOP-NIDDM trial. A 2.7-fold increase in the risk of diabetes was observed in female carriers of the C allele of rs6902123 (95% CI 1.44-5.30; adjusted P = 0.002). In the placebo group, subjects possessing both the 482Ser allele of the PPAR-gamma coactivator-la gene (PGC-1A) and the rare allele of two SNPs of PPARD (rs6902123 and rs3734254) had up to 2.5-fold increased risk for diabetes. Furthermore, women carrying the C allele of rs6902123 of PPARD and the Pro12Pro genotype of the PPAR-gamma 2 gene (PPARG2) had a 3.9-fold (95% CI 1.79-8.63; P = 0.001)-higher risk for diabetes than women with protective genotypes. Expression levels of PPAR-delta in subcutaneous adipose tissue of 87 offspring of Finnish patients with type 2 diabetes did not differ among the genotype groups of SNPs of PPARD. We conclude that SNPs in PPARD modify the conversion from IGT to type 2 diabetes, particularly in combination with the SNPs of PGC-1A and PPARG2.
引用
收藏
页码:2148 / 2152
页数:5
相关论文
共 25 条
[1]   A haplotype map of the human genome [J].
Altshuler, D ;
Brooks, LD ;
Chakravarti, A ;
Collins, FS ;
Daly, MJ ;
Donnelly, P ;
Gibbs, RA ;
Belmont, JW ;
Boudreau, A ;
Leal, SM ;
Hardenbol, P ;
Pasternak, S ;
Wheeler, DA ;
Willis, TD ;
Yu, FL ;
Yang, HM ;
Zeng, CQ ;
Gao, Y ;
Hu, HR ;
Hu, WT ;
Li, CH ;
Lin, W ;
Liu, SQ ;
Pan, H ;
Tang, XL ;
Wang, J ;
Wang, W ;
Yu, J ;
Zhang, B ;
Zhang, QR ;
Zhao, HB ;
Zhao, H ;
Zhou, J ;
Gabriel, SB ;
Barry, R ;
Blumenstiel, B ;
Camargo, A ;
Defelice, M ;
Faggart, M ;
Goyette, M ;
Gupta, S ;
Moore, J ;
Nguyen, H ;
Onofrio, RC ;
Parkin, M ;
Roy, J ;
Stahl, E ;
Winchester, E ;
Ziaugra, L ;
Shen, Y .
NATURE, 2005, 437 (7063) :1299-1320
[2]   Common polymorphisms of the PPAR-γ2 (Pro12Ala) and PGC-1α (Gly482Ser) genes are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial [J].
Andrulionytè, L ;
Zacharova, J ;
Chiasson, JL ;
Laakso, M .
DIABETOLOGIA, 2004, 47 (12) :2176-2184
[3]   Haploview: analysis and visualization of LD and haplotype maps [J].
Barrett, JC ;
Fry, B ;
Maller, J ;
Daly, MJ .
BIOINFORMATICS, 2005, 21 (02) :263-265
[4]   Lipids and glucose in type 2 diabetes - What is the cause and effect? [J].
Boden, G ;
Laakso, M .
DIABETES CARE, 2004, 27 (09) :2253-2259
[5]   The STOP-NIDDM Trial -: An international study on the efficacy of an α-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance:: rationale, design, and preliminary screening data [J].
Chiasson, JL ;
Gomis, R ;
Hanefeld, M ;
Josse, RG ;
Karasik, A ;
Laakso, M .
DIABETES CARE, 1998, 21 (10) :1720-1725
[6]   Acarbose for prevention of type 2 diabetes mellitus: the STOPNIDDM randomised trial [J].
Chiasson, JL ;
Josse, RG ;
Gomis, R ;
Hanefeld, M ;
Karasik, A ;
Laakso, M .
LANCET, 2002, 359 (9323) :2072-2077
[7]   Mutation analysis of peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) and relationships of identified amino acid polymorphisms to Type II diabetes mellitus [J].
Ek, J ;
Andersen, G ;
Urhammer, SA ;
Gæde, PH ;
Drivsholm, T ;
Borch-Johnsen, K ;
Hansen, T ;
Pedersen, O .
DIABETOLOGIA, 2001, 44 (12) :2220-2226
[8]   Peroxisome proliferator-activated receptor-γ coactivator-1 gene locus -: Associations with obesity indices in middle-aged women [J].
Esterbauer, H ;
Oberkofler, H ;
Linnemayr, V ;
Iglseder, B ;
Hedegger, M ;
Wolfsgruber, P ;
Paulweber, B ;
Fastner, G ;
Krempler, F ;
Patsch, W .
DIABETES, 2002, 51 (04) :1281-1286
[9]  
Gavin JR, 2001, AM J CARDIOL, V88, p4H, DOI 10.1016/S0002-9149(01)01830-6
[10]   Regulatory role of peroxisome proliferator-activated receptor delta (PPARδ) in muscle metabolism.: A new target for metabolic syndrome treatment? [J].
Grimaldi, PA .
BIOCHIMIE, 2005, 87 (01) :5-8