Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions.
Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions.
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DOI：
10.1289/ehp.9166
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发表时间：
2006-10
影响因子：
10.4
通讯作者：
NTD Collaborative Group
中科院分区：
文献类型：
--
作者：
Boyles AL;Billups AV;Deak KL;Siegel DG;Mehltretter L;Slifer SH;Bassuk AG;Kessler JA;Reed MC;Nijhout HF;George TM;Enterline DS;Gilbert JR;Speer MC;NTD Collaborative Group
叶酸代谢途径基因已经被研究与神经管缺陷(NTDS)有关，因为补充叶酸可以降低这种衰弱的出生缺陷的风险。大多数研究都是单独处理这些基因，往往不同的人群提供了相互矛盾的结果。我们的研究评估了几个叶酸途径基因与人类NTDS的关联，其中包括一个环境辅助因素：母体叶酸补充。在304个患有脊髓脊膜膨出或无脑畸形的美国高加索NTD家系中，我们检测了11个基因的28个多态性：叶酸受体1、叶酸受体2、溶质载体家族19个成员1、转钴素II、亚甲基四氢叶酸脱氢酶1、丝氨酸羟甲基转移酶1、5，10-亚甲基四氢叶酸还原酶(MTHFR)、5-甲基四氢叶酸-同型半胱氨酸甲基转移酶、5-甲基四氢叶酸-同型半胱氨酸甲基转移酶、甜菜碱-同型半胱氨酸甲基转移酶(BHMT)和半胱氨酸-β-合成酶。在整个数据集中，只有BHMT中的单核苷酸多态(SNPs)显著相关；当母亲在受孕前服用含有叶酸的营养补充剂时，这一意义最强。当数据按MTHFR rs1801133不耐热T等位基因从亲本向后代优先传递时，BHMT SNP rs3733890的意义更为显著。根据母体补充、MTHFR或BHMT等位基因传递进行分层时，叶酸途径基因中的其他SNP在某些分析中略显着。在我们的数据集中，BHMT rs3733890显著相关，而MTHFR rs1801133不是主要危险因素。对叶酸和蛋氨酸循环基因的进一步研究将需要广泛的SNP基因分型和/或重新测序，以确定新的变种，纳入环境因素，并在大数据集中调查基因-基因相互作用。
Folate metabolism pathway genes have been examined for association with neural tube defects (NTDs) because folic acid supplementation reduces the risk of this debilitating birth defect. Most studies addressed these genes individually, often with different populations providing conflicting results. Our study evaluates several folate pathway genes for association with human NTDs, incorporating an environmental cofactor: maternal folate supplementation. In 304 Caucasian American NTD families with myelomeningocele or anencephaly, we examined 28 polymorphisms in 11 genes: folate receptor 1, folate receptor 2, solute carrier family 19 member 1, transcobalamin II, methylenetetrahydrofolate dehydrogenase 1, serine hydroxymethyl-transferase 1, 5,10-methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homo-cysteine methyltransferase, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase, betaine-homocysteine methyltransferase (BHMT), and cystathionine-beta-synthase. Only single nucleotide polymorphisms (SNPs) in BHMT were significantly associated in the overall data set; this significance was strongest when mothers took folate-containing nutritional supplements before conception. The BHMT SNP rs3733890 was more significant when the data were stratified by preferential transmission of the MTHFR rs1801133 thermolabile T allele from parent to offspring. Other SNPs in folate pathway genes were marginally significant in some analyses when stratified by maternal supplementation, MTHFR, or BHMT allele transmission. BHMT rs3733890 is significantly associated in our data set, whereas MTHFR rs1801133 is not a major risk factor. Further investigation of folate and methionine cycle genes will require extensive SNP genotyping and/or resequencing to identify novel variants, inclusion of environmental factors, and investigation of gene–gene interactions in large data sets.
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影响因子：
3.8
作者：
Afman, LA;Lievers, KJA;Blom, HJ
通讯作者：
Blom, HJ
影响因子：
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Kaplan, NL
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作者：
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Orozco-Orozco, L
影响因子：
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Kaplan, NL
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作者：
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ESKES, TKAB