Gene-Folic Acid Interactions and Risk of Conotruncal Heart Defects: Results from the National Birth Defects Prevention Study.
Gene-Folic Acid Interactions and Risk of Conotruncal Heart Defects: Results from the National Birth Defects Prevention Study.
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DOI：
10.3390/genes14010180
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发表时间：
2023-01-09
期刊：
影响因子：
3.5
通讯作者：
Natl Birth Defects Prevention Study
中科院分区：
文献类型：
--
作者：
Webber, Daniel M. M.;Li, Ming;MacLeod, Stewart L. L.;Tang, Xinyu;Levy, Joseph W. W.;Karim, Mohammad A. A.;Erickson, Stephen W. W.;Hobbs, Charlotte A. A.;Natl Birth Defects Prevention Study
圆锥动脉干心脏缺陷（CTD）是影响心脏流出道的心脏畸形，通常会导致显著的发病率和死亡率。来自流行病学研究的证据表明，母体叶酸摄入量与心脏缺陷（包括CTD）风险降低有关。然而，目前还不清楚叶酸相关基因变异和母亲叶酸摄入量是否对CTD的风险有交互作用。在这项研究中，我们对来自436个CTD病例家庭的DNA进行了叶酸相关基因的靶向测序，这些家庭参加了国家出生缺陷预防研究，然后检测了与CTD相关的常见和罕见变异。我们确定了母亲MTHFS的风险等位基因，（ORmeta = 1.34; 95% CI 1.07 - 1.67），母体NOS 2（ORmeta = 1.34; 95% CI 1.05 - 1.72），胎儿MTHFS（ORmeta = 1.35; 95%CI 1.09 - 1.66）和胎儿TCN 2（ORmeta = 1.38; 95%CI 1.12 - 1.70）与未补充叶酸病例中CTD风险增加相关。我们检测了叶酸、同型半胱氨酸和转硫途径基因中假定的新生突变，并确定了MGST 1罕见变异与CTD风险之间的显著相关性。结果表明，围受孕期补充叶酸与易感基因型个体CTD风险降低相关。
Conotruncal heart defects (CTDs) are heart malformations that affect the cardiac outflow tract and typically cause significant morbidity and mortality. Evidence from epidemiological studies suggests that maternal folate intake is associated with a reduced risk of heart defects, including CTD. However, it is unclear if folate-related gene variants and maternal folate intake have an interactive effect on the risk of CTDs. In this study, we performed targeted sequencing of folate-related genes on DNA from 436 case families with CTDs who are enrolled in the National Birth Defects Prevention Study and then tested for common and rare variants associated with CTD. We identified risk alleles in maternal MTHFS (ORmeta = 1.34; 95% CI 1.07 to 1.67), maternal NOS2 (ORmeta = 1.34; 95% CI 1.05 to 1.72), fetal MTHFS (ORmeta = 1.35; 95% CI 1.09 to 1.66), and fetal TCN2 (ORmeta = 1.38; 95% CI 1.12 to 1.70) that are associated with an increased risk of CTD among cases without folic acid supplementation. We detected putative de novo mutations in genes from the folate, homocysteine, and transsulfuration pathways and identified a significant association between rare variants in MGST1 and CTD risk. Results suggest that periconceptional folic acid supplementation is associated with decreased risk of CTD among individuals with susceptible genotypes.
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影响因子：
3.5
作者：
Diab NS;Barish S;Dong W;Zhao S;Allington G;Yu X;Kahle KT;Brueckner M;Jin SC
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作者：
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通讯作者：
JOLIVET, J
影响因子：
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作者：
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Wald, N