Gene variants in the folate-mediated one-carbon metabolism (FOCM) pathway as risk factors for conotruncal heart defects.
Gene variants in the folate-mediated one-carbon metabolism (FOCM) pathway as risk factors for conotruncal heart defects.
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DOI：
10.1002/ajmg.a.35313
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发表时间：
2012-05
影响因子：
2
通讯作者：
Shaw, Gary M.
中科院分区：
文献类型：
--
作者：
Zhu, Huiping;Yang, Wei;Lu, Wei;Etheredge, Analee J.;Lammer, Edward J.;Finnell, Richard H.;Carmichael, Suzan L.;Shaw, Gary M.
我们评估了四种叶酸介导的一碳代谢途径基因MTHFD 1、SHMT 1、MTHFR和DHFR中的35种变异作为圆锥动脉干心脏缺陷的危险因素。排除诊断为单基因疾病或染色体异常的病例。对照组是从地区医院中按其对活产婴儿总人口的贡献比例随机选择的。计算每个基因型（纯合变异体或杂合子，与纯合野生型）和每个不太常见的等位基因的增加（对数加性模型）的比值比（OR）和95%置信区间。每个变量和三个叶酸摄入量变量（母亲使用多种维生素，母亲膳食叶酸摄入量和合并的母亲叶酸摄入量）之间的相互作用也进行了评估下的对数相加模型。总的来说，我们没有发现显著的关联。MTHFD 1 rs 11627387的A等位基因与西班牙裔母亲（OR=1.7，95%CI =1.1 ~ 2.5）和西班牙裔婴儿（OR = 1.7，95%CI =1.2 ~ 2.3）圆锥动脉干缺陷风险增加1.7倍相关。MTHFR rs 1801133的T等位基因与饮食叶酸摄入量≤ 25百分位数的西班牙裔女性的风险增加2.8倍相关。MTHFR rs 1801131的C等位基因仅在膳食叶酸摄入量>第25百分位数的人群中与风险增加2倍相关（OR=2.0，95%CI=1.0 ~ 3.9）。我们的研究表明，在西班牙裔中，MTHFD 1 rs 11627387可能通过母体和后代基因型效应与圆锥干缺陷的风险相关。母亲MTHFR基因的功能变异可能与膳食叶酸摄入量相互作用，并改变后代圆锥动脉干缺陷的风险。
We evaluated 35 variants among four folate-mediated one-carbon metabolism pathway genes, MTHFD1, SHMT1, MTHFR, and DHFR as risk factors for conotruncal heart defects. Cases with a 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. Odds Ratios (OR) and the 95% confidence intervals were computed for each genotype (homozygous variant or heterozygote, versus homozygous wildtype) and for increase of each less common allele (log-additive model). Interactions between each variant and three folate intake variables (maternal multivitamin use, maternal dietary folate intake, and combined maternal folate intake) were also evaluated under the log-additive model. In general, we did not identify notable associations. The A allele of MTHFD1 rs11627387 was associated with a 1.7-fold increase in conotruncal defects risk in both Hispanic mothers (OR=1.7, 95% CI=1.1∼2.5) and Hispanic infants (OR=1.7, 95% CI=1.2∼2.3). The T allele of MTHFR rs1801133 was associated with a 2.8-fold increase of risk among Hispanic women whose dietary folate intake was ≤ 25th centile. The C allele of MTHFR rs1801131 was associated with a two-fold increase of risk (OR=2.0, 95%CI=1.0∼3.9) only among those whose dietary folate intake was >25th centile. Our study suggested that MTHFD1 rs11627387 may be associated with risk of conotruncal defects through both maternal and offspring genotype effect among the Hispanics. Maternal functional variants in MTHFR gene may interact with dietary folate intake and modify the conotruncal defects risk in the offspring.
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影响因子：
2
作者：
Shaw, GM;Iovannisci, DM;Lammer, EJ
通讯作者：
Lammer, EJ
影响因子：
5.2
作者：
Parle-McDermott, Anne;Kirke, Peadar N.;Scott, John M.
通讯作者：
Scott, John M.
DOI：
10.1002/bdra.20541
发表时间：
2009-01-01
影响因子：
--
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：
FERENCZ, C;RUBIN, JD;DOWNING, JW
通讯作者：
DOWNING, JW
叶酸代谢途径中的基因 - 基因相互作用和共鸣心脏缺陷的风险。
影响因子：
--
作者：
Lupo PJ;Goldmuntz E;Mitchell LE
通讯作者：
Mitchell LE