Genetic determinants of adiponectin regulation revealed by pregnancy.


This study investigated genetic determinants of adiponectin during pregnancy to reveal novel biology of adipocyte regulation.


A genome-wide association study was conducted in 1,322 pregnant women from the Hyperglycemia and Adverse Pregnancy Outcome Study with adiponectin measured at ∼28 weeks of gestation. Variants reaching P < 5×10(-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.


In the combined meta-analysis, the maternal T allele of rs900400 located on chr3q25 (near LEKR1/CCNL1) was associated with lower maternal adiponectin (β ± standard error [SE] = -0.18 ± 0.03 standard deviation [SD] of adiponectin per risk allele; P = 1.5 ×10(-8) ; N = 2,004; multivariable adjusted models). In contrast, rs900400 showed only nominal association with adiponectin in a large sample of nonpregnant women (β ± 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 (β ±SE = 0.19 ± 0.04 SD per risk allele; P = 4.1×10(-8) ; N = 1,489) and higher cord blood leptin (β ± SE = 0.28 ± 0.05 log-leptin per risk allele; P = 8.2 ×10(-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.


These investigations of adipokines during pregnancy and early life suggest that rs900400 has a role in adipocyte function.

Obesity (Silver Spring)
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Genetic determinants of adiponectin regulation revealed by pregnancy.
Hivert MF, Scholtens DM, Allard C, Nodzenski M, Bouchard L, Brisson D, Lowe LP, McDowell I, Reddy T, Dastani Z, Richards JB, Hayes MG, Lowe WL