Investigation of folate pathway gene polymorphisms and the incidence of neural tube defects in a Texas Hispanic population
Investigation of folate pathway gene polymorphisms and the incidence of neural tube defects in a Texas Hispanic population
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DOI：
10.1006/mgme.2000.2991
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发表时间：
2000-05-01
影响因子：
3.8
通讯作者：
Finnell, R
中科院分区：
文献类型：
--
作者：
Barber, R;Shalat, S;Finnell, R
神经管缺陷（NTDs）的病因是多因素的，遗传和环境因素都有助于其发展。最近的证据表明，围受孕期补充母亲的饮食与多种维生素含有叶酸显着降低发生和复发的风险，有妊娠并发神经管畸形。不幸的是，叶酸的有益作用的机制仍然未知。得克萨斯-墨西哥边境的NTD监测数据显示，1990-1991年卡梅隆县NTD集群期间注意到的高NTD率（28/10，000活产）叠加在背景卡梅隆县NTD率（16/10，000 5胎）上，该比率大大高于美国的一般记录（8-10/10，000活产）。这些数据表明，遗传因素以及短暂的环境因素可能有助于NTD的病因。此外，临床和实验证据表明，参与叶酸代谢和/或转运的基因的等位基因形式可能解释了在不同人群中发现的NTD率的一些观察到的变化。本研究选择了两个叶酸途径基因进行评估。研究的基因座包括5，10-亚甲基四氢叶酸还原酶（MTHFR）基因的两个已知等位基因，以及叶酸受体-α（FR-α）基因的启动子区。MTHFR基因C677 T多态性的优势比（OR）为1.8（CI 0.47-6.8）的杂合性和1.8（CI 0.35-9.4）的纯合性的突变677 T等位基因，相对于野生型纯合子。同一基因A1298 C多态性的杂合性比值比为1.1（CI 0.09-14）。未观察到1298 C等位基因纯合子个体。FR-cy基因第762位和第610/631位核苷酸多态性的杂合性OR值分别为1.4和0.7。FR-α多态性均未在纯合子条件下观察到。由于所有OR的95%置信区间均包含1，因此未观察到任何多态性的统计学显著相关性。然而，MTHFR 677 T等位基因在来自德克萨斯州的西班牙裔对照组中的频率与其他人群显著不同（P < 0.005），并且在所检查的任何对照人群中报告的频率最高。(C)北京大学出版社.
Neural tube defects (NTDs) are multifactorial in their etiology, having both genetic and environmental factors contributing to their development. Recent evidence demonstrates that periconceptional supplementation of the maternal diet with a multivitamin containing folic acid significantly reduces the occurrence and recurrence risk for having a pregnancy complicated by NTDs. Unfortunately, the mechanism underlying the beneficial effects of folic acid remains unknown. NTD surveillance data from the Texas-Mexico border show that the high NTD rate (28/10,000 live births) noted during the 1990-1991 Cameron county NTD cluster was superimposed on a background Cameron county NTD rate (16/10,000 five births) which is considerably higher than that generally noted in the United States (8-10/10,000 live births). These data suggest that genetic factors as well as transient environmental factors may contribute to the etiology of the NTDs. Furthermore, clinical and experimental evidence imply that allelic forms of genes involved with folate metabolism and/or transport may explain some of the observed variation in the NTD rates found across different populations. Two folate pathway genes were selected for evaluation in this study. The loci investigated included two known alleles of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, as well as the promoter region of the folate receptor-alpha (FR-alpha) gene. Odds ratios (ORs) for the C677T polymorphism in the MTHFR gene were 1.8 (CI 0.47-6.8) for heterozygosity and 1.8 (CI 0.35-9.4) for homozygosity for the mutant 677T allele, relative to wildtype homozygotes. The odds ratio for the heterozygosity for the A1298C polymorphism in the same gene was 1.1 (CI 0.09-14). No individuals homozygous for the 1298C allele were observed. The OR for heterozygosity of FR-cy gene polymorphisms detected at nucleotide 762 and at nucleotides 610/631 was 1.4 and 0.7, respectively. Neither of the FR-alpha polymorphisms was observed in the homozygous condition. No statistically significant associations were observed for any of the polymorphisms examined, as the 95% confidence intervals for all of the ORs included one. However, the frequency of the MTHFR 677T allele in the largely Hispanic control group from Texas was significantly different from other populations (P < 0.005), and among the highest reported for any control populations examined. (C) 2000 Academic Press.