Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 May;25(5):935-944.
doi: 10.1002/oby.21805. Epub 2017 Mar 20.

Genetic determinants of adiponectin regulation revealed by pregnancy

Marie-France Hivert  1   2   3 , Denise M Scholtens  4 , Catherine Allard  5 , Michael Nodzenski  4 , Luigi Bouchard  6 , Diane Brisson  7 , Lynn P Lowe  8 , Ian McDowell  9 , Tim Reddy  9 , Zari Dastani  10 , J Brent Richards  11   12 , M Geoffrey Hayes  13 , William L Lowe Jr  13
Affiliations

Genetic determinants of adiponectin regulation revealed by pregnancy

Marie-France Hivert et al. Obesity (Silver Spring). 2017 May.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Regional plots of 3q25 (Figure 1a) and of 3q27 (Figure 1b) for association with maternal adiponectin levels measured at 2nd trimester. Pink diamond indicated P-value of meta-analysis for fully adjusted Model 2.
Figure 2
Figure 2
Cord blood leptin levels (Figure 2a; N=502) and adiponectin levels (Figure 2b; N=495) for each genotype at rs900400 in Gen3G newborns. Results presented for model 2, adjusted for maternal age, parity, gestational age at birth, newborn gender, and for maternal BMI
See this image and copyright information in PMC

References

    1. Meyer LK, Ciaraldi TP, Henry RR, Wittgrove AC, Phillips SA. Adipose tissue depot and cell size dependency of adiponectin synthesis and secretion in human obesity. Adipocyte. 2013;2:217–226. - PMC - PubMed
    1. Hivert MF, Sullivan LM, Fox CS, Nathan DM, D'Agostino RB, Sr, Wilson PW, et al. Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance. J Clin Endocrinol Metab. 2008;93:3165–3172. - PMC - PubMed
    1. Hivert MF, Sullivan LM, Shrader P, Fox CS, Nathan DM, D'Agostino RB, Sr, et al. Insulin resistance influences the association of adiponectin levels with diabetes incidence in two population-based cohorts: the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study and the Framingham Offspring Study. Diabetologia. 2011;54:1019–1024. - PMC - PubMed
    1. Lacroix M, Battista MC, Doyon M, Menard J, Ardilouze JL, Perron P, et al. Lower adiponectin levels at first trimester of pregnancy are associated with increased insulin resistance and higher risk of developing gestational diabetes mellitus. Diabetes Care. 2013;36:1577–1583. - PMC - PubMed
    1. Dastani Z, Hivert MF, Timpson N, Perry JR, Yuan X, Scott RA, et al. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet. 2012;8:e1002607. - PMC - PubMed

LinkOut - more resources