OBJECTIVE: The main purpose of this study was to investigate associations of single-nucleotide polymorphisms (SNPs) in the adipocyte C1q and collagen domain-containing (ACDC) gene and its regulator, the nuclear peroxisome proliferator-activated receptor (PPAR)-gamma gene, with body fat mass and its topographical distribution in postmenopausal women. RESEARCH METHODS AND PROCEDURES: Participants were 1501 healthy women, 60 to 85 years old, who were genotyped for four SNPs in the ACDC gene (-11391G/A, -11377C/G, +45T/G, +276G/T) and the Pro12Ala SNP in the PPAR-gamma gene. Total body fat mass and the central to peripheral fat mass ratio (CFM/PFM ratio) were measured using DXA. Adiponectin and homeostasis model assessment of insulin resistance were measured in 287 subjects. RESULTS: The -11377C/G SNP was associated with adiponectin (p < 0.001) and the CFM/PFM ratio (p = 0.005); the G allele being associated with low adiponectin and high CFM/PFM ratio. Similar associations of adiponectin (p = 0.0001) and the CFM/PFM ratio (p = 0.002) characterized the 1_2 (G_G) promoter haplotype (11391G/A_-11377C/G). Genotype variation of SNP Pro12Ala was associated with total body fat mass (p = 0.04); women with GG being the most obese (p = 0.01). The Ala/Ala (GG) genotype of Pro12Ala SNP interacted with the CC genotype of SNP-11377C/G in the determination of BMI (p = 0.001), when analyzed using a codominant model. DISCUSSION: Polymorphisms in the ACDC gene are associated with body fat distribution, whereas the Pro12Ala polymorphism in PPAR-gamma is associated with overall adiposity, apparently in interaction with an ACDC promoter SNP.
OBJECTIVE: The main purpose of this study was to investigate associations of single-nucleotide polymorphisms (SNPs) in the adipocyte C1q and collagen domain-containing (ACDC) gene and its regulator, the nuclear peroxisome proliferator-activated receptor (PPAR)-gamma gene, with body fat mass and its topographical distribution in postmenopausal women. RESEARCH METHODS AND PROCEDURES: Participants were 1501 healthy women, 60 to 85 years old, who were genotyped for four SNPs in the ACDC gene (-11391G/A, -11377C/G, +45T/G, +276G/T) and the Pro12Ala SNP in the PPAR-gamma gene. Total body fat mass and the central to peripheral fat mass ratio (CFM/PFM ratio) were measured using DXA. Adiponectin and homeostasis model assessment of insulin resistance were measured in 287 subjects. RESULTS: The -11377C/G SNP was associated with adiponectin (p < 0.001) and the CFM/PFM ratio (p = 0.005); the G allele being associated with low adiponectin and high CFM/PFM ratio. Similar associations of adiponectin (p = 0.0001) and the CFM/PFM ratio (p = 0.002) characterized the 1_2 (G_G) promoter haplotype (11391G/A_-11377C/G). Genotype variation of SNP Pro12Ala was associated with total body fat mass (p = 0.04); women with GG being the most obese (p = 0.01). The Ala/Ala (GG) genotype of Pro12Ala SNP interacted with the CC genotype of SNP-11377C/G in the determination of BMI (p = 0.001), when analyzed using a codominant model. DISCUSSION: Polymorphisms in the ACDC gene are associated with body fat distribution, whereas the Pro12Ala polymorphism in PPAR-gamma is associated with overall adiposity, apparently in interaction with an ACDC promoter SNP.
Authors: Sarah S Cohen; Marilie D Gammon; Kari E North; Robert C Millikan; Ethan M Lange; Scott M Williams; Wei Zheng; Qiuyin Cai; Jirong Long; Jeffrey R Smith; Lisa B Signorello; William J Blot; Charles E Matthews Journal: Obesity (Silver Spring) Date: 2011-01-27 Impact factor: 5.002