Volcik K A, Blanton S H, Tyerman G H, Jong S T, Rott E J, Page T Z, Romaine N K, Northrup H
Department of Pediatrics, The University of Texas-Houston Medical School, Houston, Texas 77030, USA.
Am J Med Genet. 2000 Nov 6;95(1):21-7.
The C677T and A1298C mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene are each associated with reduced MTHFR activity. The C677T mutation in the heterozygous and homozygous state correlates with increased enzyme thermolability, with homozygous mutant genotypes showing significantly elevated plasma homocysteine levels and decreased plasma folate levels. The A1298C mutation results in decreased MTHFR activity, but changes in neither homocysteine nor folate levels are associated with A1298C variant genotypes. Our study determined the frequencies of the C677T and A1298C MTHFR mutations for spina bifida (SB) cases, mothers and fathers of SB cases, and controls in Hispanics of Mexican-American descent. In addition, our subject population was further categorized as to whether the spina bifida lesion occurred as an upper or lower level defect, according to the Van Allen "multi-site closure" model. Hispanic SB cases with upper level defects and their mothers were homozygous for the C677T variant allele at a higher rate than their respective controls (OR = 1.5 [95% CI 0.8-2.9], P = 0.30; OR = 2.3 [1.1-4.8], P = 0.04, respectively), with statistically significant results seen only for the maternal homozygous genotype. Homozygosity for the A1298C mutation was seen at a higher rate only in Hispanic mothers of both upper and lower level SB cases when compared to controls, but these results were not statistically significant. Our study provides evidence that the maternal C677T MTHFR homozygous mutant genotype is a risk factor for upper level spina bifida defects in Hispanics.
5,10-亚甲基四氢叶酸还原酶（MTHFR）基因中的C677T和A1298C突变均与MTHFR活性降低有关。杂合子和纯合子状态的C677T突变与酶的热不稳定性增加相关，纯合突变基因型显示血浆同型半胱氨酸水平显著升高，血浆叶酸水平降低。A1298C突变导致MTHFR活性降低，但同型半胱氨酸和叶酸水平的变化与A1298C变异基因型无关。我们的研究确定了墨西哥裔西班牙裔脊柱裂（SB）病例、SB病例的父母以及对照人群中C677T和A1298C MTHFR突变的频率。此外，根据范·艾伦“多部位闭合”模型，我们的研究人群进一步分为脊柱裂病变发生在上部或下部缺陷。患有上部缺陷的西班牙裔SB病例及其母亲的C677T变异等位基因纯合率高于各自的对照组（OR = 1.5 [95% CI 0.8 - 2.9]，P = 0.30；OR = 2.3 [1.1 - 4.8]，P = 0.04），仅母亲的纯合基因型有统计学显著结果。与对照组相比，仅在上下部SB病例的西班牙裔母亲中，A1298C突变的纯合率较高，但这些结果无统计学意义。我们的研究提供了证据，表明母亲的C677T MTHFR纯合突变基因型是西班牙裔上部脊柱裂缺陷的一个风险因素。
