Genetic determinants of adiponectin regulation revealed by pregnancy

Marie France Hivert*, Denise M. Scholtens, Catherine Allard, Michael Nodzenski, Luigi Bouchard, Diane Brisson, Lynn P. Lowe, Ian McDowell, Tim Reddy, Zari Dastani, J. Brent Richards, M. Geoffrey Hayes, William L. Lowe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 < 5×10−5 for de novo genotyping in two replication cohorts (Genetics of Glycemic regulation in Gestation and Growth N = 522; ECOGENE-21 N = 174) were selected. Results: 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. Conclusions: These investigations of adipokines during pregnancy and early life suggest that rs900400 has a role in adipocyte function.

Original languageEnglish (US)
Pages (from-to)935-944
Number of pages10
JournalObesity
Volume25
Issue number5
DOIs
StatePublished - May 2017

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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