Thymidylate synthase polymorphisms and risk of conotruncal heart defects.
Thymidylate synthase polymorphisms and risk of conotruncal heart defects.
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DOI：
10.1002/ajmg.a.35310
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发表时间：
2012-09
影响因子：
2
通讯作者：
Lammer, Edward J.
中科院分区：
文献类型：
--
作者：
Zhu, Huiping;Yang, Wei;Shaw, Nathan;Perloff, Spencer;Carmichael, Suzan L.;Finnell, Richard H.;Shaw, Gary M.;Lammer, Edward J.
在这项研究中，我们调查了两种 TYMS 功能变异（28bp VNTR 和 1494del6）（275 例病例和 653 名对照）和 6 个选定的 SNP（265 例婴儿、535 名对照婴儿；169 例母亲和 276 名对照母亲）是否与圆锥动脉心脏缺陷的风险相关。此外，我们还评估了这些基因变异与母体叶酸摄入量之间的相互作用对 CTD 风险的影响。诊断为单基因疾病或染色体异常的病例被排除在外。对照组是根据其对活产婴儿总数的贡献比例从地区医院中随机选择的。 DNA 样本是使用口腔刷采集的，或者是从新生儿筛查血液样本库中提取的（如果有）。遗传变异被视为分类变量（纯合子、杂合子、纯合子变异）。使用逻辑回归计算优势比和 95% 置信区间 (CI)，分别估计所有受试者（西班牙裔和非西班牙裔白人）的风险。通过向逻辑模型添加相互作用项来评估这些变体的基因-叶酸相互作用。通过将母亲围孕期使用含叶酸的维生素补充剂与每日膳食叶酸摄入量相结合，创建了一个二分复合变量“联合叶酸摄入量”。一般来说，结果并未显示出仅基因对 CTD 风险的强烈影响。然而，我们确实观察到 3'-非翻译区 (UTR) (1694del6) 6bp 缺失的纯合子婴儿以及母亲在围孕期叶酸摄入量较低的情况下，CTD 风险增加了 3.6 倍 (95%CI:1.1 – 11.9)。
In this study, we investigated whether the two TYMS functional variants (28bp VNTR and 1494del6) (275 cases and 653 controls) and six selected SNPs (265 case infants, 535 control infants; 169 case mothers and 276 control mothers) were associated with risks of conotruncal heart defects. Further, we evaluated interaction effects between these gene variants and maternal folate intake for risk of CTD. Cases with diagnosis of single gene disorders or chromosomal aneusomies were excluded. Controls were randomly selected from area hospitals in proportion to their contribution to the total population of live-born infants. DNA samples were collected using buccal brushes or drawn from the repository of newborn screening blood specimens when available. Genetic variants were treated as categorical variables (homozygous referent, heterozygote, homozygous variant). Odds ratios and 95% confidence intervals (CI) were computed to estimate risks among all subjects, Hispanic and non-Hispanic whites, respectively using logistic regression. Gene-folate interactions were assessed for these variants by adding an interaction term to the logistic model. A dichotomized composite variable, “combined folate intake”, was created by combining maternal peri-conceptional use of folic acid-containing vitamin supplements with daily dietary intake of folate. In general, the results do not show strong gene-only effects on risk of CTD. We did, however, observe a 3.6-fold increase in CTD risk (95%CI:1.1 – 11.9) among infants who were homozygotes for the 6bp deletion in the 3’-untranslated region (UTR) (1694del6) and whose mothers had low folate intake during the peri-conceptional period.
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DOI：
10.1016/s0925-4439(02)00080-7
发表时间：
2002-07-18
影响因子：
6.2
作者：
Liu, J;Schmitz, JC;Chu, E
通讯作者：
Chu, E
DOI：
10.1002/bdra.20541
发表时间：
2009-01-01
影响因子：
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作者：
Lammer, Edward J.;Chak, Jacqueline S.;Shaw, Gary M.
通讯作者：
Shaw, Gary M.
影响因子：
5
作者：
BLOCK, G;HARTMAN, AM;GARDNER, L
通讯作者：
GARDNER, L
DOI：
10.1002/bdra.20745
发表时间：
2011-01
影响因子：
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作者：
Lupo, Philip J.;Mitchell, Laura E.;Goldmuntz, Elizabeth
通讯作者：
Goldmuntz, Elizabeth
影响因子：
7.1
作者：
Cho, E;Zeisel, SH;Willett, WC
通讯作者：
Willett, WC