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. 2014 Jan;78(1):23-32.
doi: 10.1111/ahg.12044.

Genetic variation in the peroxisome proliferator-activated receptor (PPAR) and peroxisome proliferator-activated receptor gamma co-activator 1 (PGC1) gene families and type 2 diabetes

Raquel Villegas  1 , Scott M Williams, Yu-Tang Gao, Jirong Long, Jiajun Shi, Hui Cai, Honglan Li, Ching-Chu Chen, E Shyong Tai; AGEN-T2D Consortium; Frank Hu, Qiuyin Cai, Wei Zheng, Xiao-Ou Shu
Affiliations

Genetic variation in the peroxisome proliferator-activated receptor (PPAR) and peroxisome proliferator-activated receptor gamma co-activator 1 (PGC1) gene families and type 2 diabetes

Raquel Villegas et al. Ann Hum Genet. 2014 Jan.

Abstract

We used a two-stage study design to evaluate whether variations in the peroxisome proliferator-activated receptors (PPAR) and the PPAR gamma co-activator 1 (PGC1) gene families (PPARA, PPARG, PPARD, PPARGC1A, and PPARGC1B) are associated with type 2 diabetes (T2D) risk. Stage I used data from a genome-wide association study (GWAS) from Shanghai, China (1019 T2D cases and 1709 controls) and from a meta-analysis of data from the Asian Genetic Epidemiology Network for T2D (AGEN-T2D). Criteria for selection of single nucleotide polymorphisms (SNPs) for stage II were: (1) P < 0.05 in single marker analysis in Shanghai GWAS and P < 0.05 in the meta-analysis or (2) P < 10(-3) in the meta-analysis alone and (3) minor allele frequency ≥ 0.10. Nine SNPs from the PGC1 family were assessed in stage II (an independent set of middle-aged men and women from Shanghai with 1700 T2D cases and 1647 controls). One SNP in PPARGC1B, rs251464, was replicated in stage II (OR = 0.87; 95% CI: 0.77-0.99). Gene-body mass index (BMI) and gene-exercise interactions and T2D risk were evaluated in a combined dataset (Shanghai GWAS and stage II data: 2719 cases and 3356 controls). One SNP in PPARGC1A, rs12640088, had a significant interaction with BMI. No interactions between the PPARGC1B gene and BMI or exercise were observed.

Keywords: PGC1; PPAR; Type 2 diabetes.

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