title: Diabetes and obesity-related genes and the risk of neural tube defects in the national birth defects prevention study.
abstract: Few studies have evaluated genetic susceptibility related to diabetes and obesity as a risk factor for neural tube defects (NTDs). The authors investigated 23 single nucleotide polymorphisms among 9 genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, SLC2A2, TCF7L2, and UCP2) associated with type 2 diabetes or obesity. Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study during 1999-2007. Log-linear models were used to evaluate maternal and offspring genetic effects. After application of the false discovery rate, there were 5 significant maternal genetic effects. The less common alleles at the 4 FTO single nucleotide polymorphisms showed a reduction of NTD risk (for rs1421085, relative risk (RR) = 0.73 (95% confidence interval (CI): 0.62, 0.87); for rs8050136, RR = 0.79 (95% CI: 0.67, 0.93); for rs9939609, RR = 0.79 (95% CI: 0.67, 0.94); and for rs17187449, RR = 0.80 (95% CI: 0.68, 0.95)). Additionally, maternal LEP rs2071045 (RR = 1.31, 95% CI: 1.08, 1.60) and offspring UCP2 rs660339 (RR = 1.32, 95% CI: 1.06, 1.64) were associated with NTD risk. Furthermore, the maternal genotype for TCF7L2 rs3814573 suggested an increased NTD risk among obese women. These findings indicate that maternal genetic variants associated with glucose homeostasis may modify the risk of having an NTD-affected pregnancy.
authors.affiliation: Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas, Houston, TX, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lupo
authors.forename: Mark A
authors.initials: MA
authors.lastname: Canfield
authors.forename: Claudia
authors.initials: C
authors.lastname: Chapa
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: A J
authors.initials: AJ
authors.lastname: Agopian
authors.forename: Laura E
authors.initials: LE
authors.lastname: Mitchell
authors.forename: Gary M
authors.initials: GM
authors.lastname: Shaw
authors.forename: D Kim
authors.initials: DK
authors.lastname: Waller
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Olshan
authors.forename: Richard H
authors.initials: RH
authors.lastname: Finnell
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000328:Adult; D003920:Diabetes Mellitus / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007231:Infant, Newborn; D016014:Linear Models; D008297:Male; D009436:Neural Tube Defects / Q000453:epidemiology* / Q000235:genetics*; D009765:Obesity / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology* / Q000235:genetics*; D012306:Risk; D014481:United States / Q000453:epidemiology