Genetic determinants of adiponectin regulation revealed by pregnancy.

ABSTRACT:

Objective

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

Methods

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 for de novo genotyping in two replication cohorts (Genetics of Glycemic regulation in Gestation and Growth N?=?522; ECOGENE-21 N?=?174) were selected.

Results

In 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 ×10^-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?=?4.1×10^-8 ; N?=?1,489) and higher cord blood leptin (??±?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.

Conclusions

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

SUBMITTER: Hivert MF 

PROVIDER: S-EPMC5404994 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature