Genetic determinants of adiponectin regulation revealed by pregnancy

ObjectiveThis study investigated genetic determinants of adiponectin during pregnancy to reveal novel biology of adipocyte regulation. MethodsA genome-wide association study was conducted in 1,322 pregnant women from the Hyperglycemia and Adverse Pregnancy Outcome Study with adiponectin measured at approximate to 28 weeks of gestation. Variants reaching P<5x10(-5) for de novo genotyping in two replication cohorts (Genetics of Glycemic regulation in Gestation and Growth N=522; ECOGENE-21 N=174) were selected. ResultsIn the combined meta-analysis, the maternal T allele of rs900400 located on chr3q25 (near LEKR1/CCNL1) was associated with lower maternal adiponectin (standard error [SE]=-0.18 +/- 0.03 standard deviation [SD] of adiponectin per risk allele; P=1.5 x10(-8); N=2,004; multivariable adjusted models). In contrast, rs900400 showed only nominal association with adiponectin in a large sample of nonpregnant women (+/- SE=-0.012 +/- 0.006; P=0.05; N=16,678 women from the ADIPOgen consortium). The offspring rs900400 T risk allele was associated with greater neonatal skinfold thickness ( +/- SE=0.19 +/- 0.04 SD per risk allele; P=4.1x10(-8); N=1,489) and higher cord blood leptin (+/- SE=0.28 +/- 0.05 log-leptin per risk allele; P=8.2 x10(-9); N=502), but not with cord blood adiponectin (P=0.23; N=495). The T allele of rs900400 was associated with higher expression of TIPARP in adipocytes. ConclusionsThese investigations of adipokines during pregnancy and early life suggest that rs900400 has a role in adipocyte function.