AHSG gene variation is not associated with regional body fat distribution--a magnetic resonance study

Obesity-resistance in AHSG-knockout mice indicate an important role of alpha2-Heremans-Schmid glycoprotein/fetuin-A (AHSG) in the development of obesity. We studied whether genetic variation within AHSG affects whole-body adiposity and regional fat distribution in humans. We genotyped 321 subjects at increased risk for type 2 diabetes for five single nucleotide polymorphisms (SNP) rs2248690, rs4831, rs2070635, rs4917, and rs1071592. Body fat distribution and ectopic hepatic and intramyocellular lipids were assessed by magnetic resonance techniques. AHSG levels were determined by immunoturbidimetry. The five chosen SNPs covered 100% of common genetic variation (minor allele frequency >/=0.05) within AHSG (r (2)>/=0.8). All SNPs were significantly associated with AHSG levels (p<0.0001), except for rs4831 (p=0.9) after adjustment for gender, age, and body mass index (BMI). AHSG levels were associated with liver fat content (p=0.0160) and BMI (p=0.0247) after adjustment for gender and age. While rs2248690 was nominally associated with BMI in the dominant model (p=0.0432), none of the SNPs was associated with regional fat distribution. Common genetic variation within AHSG does not appear to influence regional body fat distribution, but may affect whole-body adiposity in humans.