Evaluation of 64 Candidate Single Nucleotide Polymorphisms as Risk Factors for Neural Tube Defects in a Large Irish Study Population

被引：27

作者：

Carter, Tonia C. ^{[1
]}

Pangilinan, Faith ^{[2
]}

Troendle, James F. ^{[1
]}

Molloy, Anne M. ^{[3
]}

VanderMeer, Julia ^{[2
]}

Mitchell, Adam ^{[2
]}

Kirke, Peadar N. ^{[4
]}

Conley, Mary R. ^{[1
]}

Shane, Barry ^{[5
]}

Scott, John M. ^{[3
]}

Brody, Lawrence C. ^{[2
]}

Mills, James L. ^{[1
]}

机构：

[1] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA

[2] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA

[3] Trinity Coll Dublin, Sch Immunol & Biochem, Dublin, Ireland

[4] Hlth Res Board Ireland, Child Hlth Epidemiol Unit, Dublin, Ireland

[5] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART A | 2011年 / 155A卷 / 01期

基金：

美国国家卫生研究院;

关键词：

congenital abnormalities; folic acid; neural tube defects; single nucleotide polymorphism; spina bifida; SPINA-BIFIDA MENINGOMYELOCELE; ALPHA-RECEPTOR; BREAST-CANCER; HUMAN T; ASSOCIATION; GENE; GENOTYPE; METABOLISM; PREVENTION; MUTATIONS;

D O I：

10.1002/ajmg.a.33755

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Individual studies of the genetics of neural tube defects (NTDs) contain results on a small number of genes in each report. To identify genetic risk factors for NTDs, we evaluated potentially functional single nucleotide polymorphisms (SNPs) that are biologically plausible risk factors for NTDs but that have never been investigated for an association with NTDs, examined SNPs that previously showed no association with NTDs in published studies, and tried to confirmpreviously reported associations in folate-related and non-folate-related genes. We investigated 64 SNPs in 34 genes for association with spina bifida in up to 558 case families (520 cases, 507 mothers, 457 fathers) and 994 controls in Ireland. Case-control and mother-control comparisons of genotype frequencies, tests of transmission disequilibrium, and log-linear regression models were used to calculate effect estimates. Spina bifida was associated with over-transmission of the LEPR (leptin receptor) rs1805134 minor C allele [genotype relative risk (GRR): 1.5; 95% confidence interval (CI): 1.0-2.1; P=0.0264] and the COMT (catechol-O-methyltransferase) rs737865 major T allele (GRR: 1.4; 95% CI: 1.1-2.0; P=0.0206). After correcting for multiple comparisons, these individual test P-values exceeded 0.05. Consistent with previous reports, spina bifida was associated with MTHFR 677C> T, T (Brachyury) rs3127334, LEPR K109R, and PDGFRA promoter haplotype combinations. The associations between LEPR SNPs and spina bifida suggest a possible mechanism for the finding that obesity is a NTD risk factor. The association between a variant in COMT and spina bifida implicates methylation and epigenetics in NTDs. (C) 2010 Wiley-Liss, Inc.

引用

页码：14 / 21

页数：8

共 43 条

[1] Promotor genotype of the platelet-derived growth factor receptor-α gene shows population stratification but not association with spina bifida meningomyelocele [J].