期刊
OBESITY
卷 25, 期 5, 页码 935-944出版社
WILEY
DOI: 10.1002/oby.21805
关键词
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资金
- NIH [R01 HD034242, R01 HD034243, U01 HG004415, R01CA141688]
- Canadian Institutes of Health Research (CIHR) Institute of Nutrition, Metabolism and Diabetes (INMD) [110791]
- American Diabetes Association (ADA)
- CR-CHUS
- Canadian Diabetes Association, FRQS - subvention Fonctionnement - Recherche Clinique [20697]
- CIHR Operating grant [INMD: MOP-115071]
- FRQS
- CIHR
- ADA Pathways Award [1-15-ACE-26]
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.
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