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

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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

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ASJC Scopus subject areas

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

Cite this

Hivert, M. F., Scholtens, D. M., Allard, C., Nodzenski, M., Bouchard, L., Brisson, D., Lowe, L. P., McDowell, I., Reddy, T., Dastani, Z., Richards, J. B., Hayes, M. G., & Lowe, W. L. (2017). Genetic determinants of adiponectin regulation revealed by pregnancy. Obesity, 25(5), 935-944. https://doi.org/10.1002/oby.21805