Evaluation of 64 candidate single nucleotide polymorphisms as risk factors for neural tube defects in a large Irish study population.
Evaluation of 64 candidate single nucleotide polymorphisms as risk factors for neural tube defects in a large Irish study population.
复制标题
在爱尔兰大型研究人群中评估 64 个候选单核苷酸多态性作为神经管缺陷的危险因素。
DOI：
10.1002/ajmg.a.33755
复制
发表时间：
2011-01
影响因子：
2
通讯作者：
Mills, James L.
中科院分区：
文献类型：
--
作者：
Carter, Tonia C.;Pangilinan, Faith;Troendle, James F.;Molloy, Anne M.;VanderMeer, Julia;Mitchell, Adam;Kirke, Peadar N.;Conley, Mary R.;Shane, Barry;Scott, John M.;Brody, Lawrence C.;Mills, James L.
关键词：
神经管缺陷（NTDs）的个体遗传学研究在每个报告中都包含少量基因的结果。为了确定NTDs的遗传危险因素，我们评估了潜在的功能性单核苷酸多态性（snp），这些snp在生物学上可能是NTDs的危险因素，但从未被研究过与NTDs的关联，检查了以前在已发表的研究中显示与NTDs没有关联的snp，并试图证实先前报道的叶酸相关和非叶酸相关基因的关联。我们在爱尔兰558个病例家庭（520例，507例母亲，457例父亲）和994个对照中调查了34个基因中的64个snp与脊柱裂相关。使用病例对照和母亲对照的基因型频率比较、传播不平衡检验和对数线性回归模型来计算效果估计。脊柱裂与LEPR（瘦素受体）rs1805134小C等位基因的过度传递相关(基因型相对风险（GRR）： 1.5；95%置信区间（CI）： 1.0, 2.1；P = 0.0264)和COMT（儿茶酚o -甲基转移酶）rs737865主要T等位基因（GRR: 1.4; 95% CI: 1.1, 2.0; P = 0.0206）。经多次比较校正后，这些个体检验的p值超过0.05。与先前的报道一致，脊柱裂与MTHFR 677C>T、T (Brachyury) rs3127334、LEPR K109R和PDGFRA启动子单倍型组合相关。LEPR snp与脊柱裂之间的关联提示肥胖是NTD危险因素的可能机制。COMT变异与脊柱裂之间的关联暗示了NTDs的甲基化和表观遗传学。
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 confirm previously 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.
登录
查看更多内容
DOI：
10.1002/bdra.20143
发表时间：
2005-07-01
影响因子：
--
作者：
Jensen, LE;Hoess, K;Mitchell, LE
通讯作者：
Mitchell, LE
DOI：
10.1002/bdra.20520
发表时间：
2009-02
影响因子：
--
作者：
Mitchell, Adam;Pangilinan, Faith;VanderMeer, Julie;Molloy, Anne M.;Troendle, James;Conley, Mary;Kirke, Peadar N.;Scott, John M.;Brody, Lawrence C.;Mills, James L.
通讯作者：
Mills, James L.
影响因子：
158.5
作者：
CZEIZEL, AE;DUDAS, I
通讯作者：
DUDAS, I
影响因子：
64.5
作者：
Okano, M;Bell, DW;Li, E
通讯作者：
Li, E
影响因子：
3.5
作者：
Parle-McDermott, A;Mills, JL;Bródy, LC
通讯作者：
Bródy, LC