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



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 < 5×10-5for de novo genotyping in two replication cohorts (Genetics of Glycemic regulation in Gestation and Growth N = 522; ECOGENE-21 N = 174) were selected.



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.



These investigations of adipokines during pregnancy and early life suggest that rs900400 has a role in adipocyte function.
Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, Massachusetts, USA.|Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Marie-France
MF
Hivert
Department of Preventive Medicine, Division of Biostatistics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Denise M
DM
Scholtens
Department of Mathematics, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Catherine
C
Allard
Department of Preventive Medicine, Division of Biostatistics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Michael
M
Nodzenski
Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Luigi
L
Bouchard
Department of Medicine, Université de Montréal, ECOGENE-21 and Lipid Clinic, Chicoutimi, Quebec, Canada.
Diane
D
Brisson
Department of Preventive Medicine, Division of Epidemiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Lynn P
LP
Lowe
Department of Biostatistics and Bioinformatics, Duke Institute for Genome Sciences and Policy, Durham, North Carolina, USA.
Ian
I
McDowell
Department of Biostatistics and Bioinformatics, Duke Institute for Genome Sciences and Policy, Durham, North Carolina, USA.
Tim
T
Reddy
Department of Internal Medicine, Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
Zari
Z
Dastani
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.|Department of Twin Research, King's College London, London, UK.
J Brent
JB
Richards
Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
M Geoffrey
MG
Hayes
Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
William L
WL
Lowe
D052242:Adiponectin / Q000097:blood / Q000235:genetics*; D000328:Adult; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D011247:Pregnancy
D052242:Adiponectin