Monsalve M V, Salzano F M, Rupert J L, Hutz M H, Hill K, Hurtado A M, Hochachka P W, Devine D V
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, B.C. Canada.
Ann Hum Genet. 2003 Jul;67(Pt 4):367-71. doi: 10.1046/j.1469-1809.2003.00027.x.
Neural tube defects (NTDs) have been associated with abnormalities of folate metabolism. Methylenetetrahydrofolate reductase (MTHFR) is the regulatory enzyme for the conversion of homocysteine to methionine. The C677T mutation in the MTHFR gene affects folate distribution, and homozygosity for the T allele may be associated with an increased risk of NTDs. A second mutation, an A1298C transversion in this same gene, is also associated with an increased risk for NTDs but only in conjunction with the 677T allele. A low incidence of NTDs has been observed in high-altitude populations; however, these studies did not provide information about the allele distribution of genes involved in folate metabolism. This investigation compares allele frequencies of the C677T and A1298C polymorphisms between Quechua people living at 3200-4200 m in the Peruvian Central Andes and an Aché group living at low altitude. Allele frequencies at both loci were not significantly different between the two populations. The absence of the 677T/677T genotypes and of the 677T/1298C arrangement in both groups may indicate a genetic contribution to reduced risk for NTDs; however, factors other than altitude are likely responsible for the low variant allele frequencies in these populations.
神经管缺陷（NTDs）与叶酸代谢异常有关。亚甲基四氢叶酸还原酶（MTHFR）是将同型半胱氨酸转化为蛋氨酸的调节酶。MTHFR基因中的C677T突变会影响叶酸分布，T等位基因纯合可能与NTDs风险增加有关。该基因的另一种突变，即A1298C颠换，也与NTDs风险增加有关，但仅与677T等位基因同时出现时才有关。在高海拔人群中观察到NTDs的发病率较低；然而，这些研究并未提供参与叶酸代谢的基因的等位基因分布信息。本研究比较了生活在秘鲁中部安第斯山脉海拔3200 - 4200米的克丘亚人与生活在低海拔的阿奇族人群中C677T和A1298C多态性的等位基因频率。两个群体在这两个位点的等位基因频率没有显著差异。两组中均不存在677T/677T基因型和677T/1298C组合，这可能表明存在一种遗传因素可降低NTDs风险；然而，除海拔以外的其他因素可能是这些人群中变异等位基因频率较低的原因。
