title: 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.
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.
authors.affiliation: Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Raquel
authors.initials: R
authors.lastname: Villegas
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Jirong
authors.initials: J
authors.lastname: Long
authors.forename: Jiajun
authors.initials: J
authors.lastname: Shi
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.forename: Honglan
authors.initials: H
authors.lastname: Li
authors.forename: Ching-Chu
authors.initials: CC
authors.lastname: Chen
authors.forename: E Shyong
authors.initials: ES
authors.lastname: Tai
authors.forename: Frank
authors.initials: F
authors.lastname: Hu
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D015444:Exercise; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins
chemical_list: D002352:Carrier Proteins; D005819:Genetic Markers; C455622:PPARGC1B protein, human; D047492:Peroxisome Proliferator-Activated Receptors; D016601:RNA-Binding Proteins
keywords: PGC1; PPAR; Type 2 diabetes