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


METHODS
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.


CONCLUSIONS
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.
Tankó
László B
LB
Center for Clinical and Basic Research, Ballerup, Denmark. lbt@ccbr.dk
Siddiq
Afshan
A
Lecoeur
Cécile
C
Larsen
Philip J
PJ
Christiansen
Claus
C
Walley
Andrew
A
Froguel
Philippe
P
D015502:Absorptiometry, Photon; D052242:Adiponectin / Q000235:genetics; D050154:Adiposity / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D050218:Body Fat Distribution; D015992:Body Mass Index; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017698:Postmenopause
C499918:ADIPOQ protein, human; D052242:Adiponectin; D047495:PPAR gamma