ACDC/adiponectin and PPAR-gamma gene polymorphisms: implications for features of obesity

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.

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.

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.

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.