Rady P L, Tyring S K, Hudnall S D, Vargas T, Kellner L H, Nitowsky H, Matalon R K
Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas 77555-0359, USA.
Am J Med Genet. 1999 Oct 8;86(4):380-4. doi: 10.1002/(sici)1096-8628(19991008)86:4<380::aid-ajmg13>3.0.co;2-9.
The polymorphic mutation C677T in the gene of MTHFR is considered a risk mutation for spina bifida and vascular disease. Another common mutation on the MTHFR gene, A1298C, has also been described as another risk mutation. We studied the frequencies of these two mutations on DNA samples from healthy Jewish individuals and compared them to the frequency of these mutations in DNA samples obtained from healthy individuals in South Texas. The presence of the C677T allele was determined by PCR and Hinf I digestion, and mutation A1298C by PCR and Mbo II digestion. A total of 310 alleles was examined for C677T in the Ashkenazi samples and 400 alleles in the non-Jewish samples. The rate of C677T among the Ashkenazi Jewish alleles was 47.7% as compared to 28.7% among the alleles from the non-Jewish population. The difference is statistically significant, P < 0.0005. Mutation A1298C was examined in 298 alleles of Jewish individuals and 374 alleles of non-Jewish counterparts from Texas. The rate of the A1298C mutation in the Jewish samples was 27.2% whereas in the non-Jewish was 35%. This was also statistically significant, P < 0.031. No individuals were homozygous for both mutations or were found to be homozygous for one mutation with heterozygosity of the other mutation, and that the C677T and the A1298C alleles did not occur in cis position. This study shows a unique distribution of C677T and the A1298C alleles among the Ashkenazi Jews. In spite of high frequency of C677T mutation, spina bifida is less common among Ashkenazi Jews. Further studies are needed to establish whether the C677T and the A1298C mutations have an impact on vascular disease in the Ashkenazi Jewish population.
亚甲基四氢叶酸还原酶（MTHFR）基因中的多态性突变C677T被认为是脊柱裂和血管疾病的风险突变。MTHFR基因上的另一种常见突变A1298C，也被描述为另一种风险突变。我们研究了来自健康犹太个体的DNA样本中这两种突变的频率，并将其与从南德克萨斯州健康个体获得的DNA样本中这些突变的频率进行比较。通过PCR和Hinf I酶切确定C677T等位基因的存在，通过PCR和Mbo II酶切确定突变A1298C。在德系犹太人样本中总共检测了310个C677T等位基因，在非犹太样本中检测了400个等位基因。德系犹太人等位基因中C677T的发生率为47.7%，而非犹太人群等位基因中的发生率为28.7%。差异具有统计学意义，P < 0.0005。在298个犹太个体等位基因和来自德克萨斯州的374个非犹太对应个体等位基因中检测了突变A1298C。犹太样本中A1298C突变的发生率为27.2%，而非犹太样本中为35%。这也具有统计学意义，P < 0.031。没有个体同时对两种突变呈纯合状态，也没有发现对一种突变呈纯合状态而对另一种突变呈杂合状态，并且C677T和A1298C等位基因不在顺式位置出现。这项研究显示了C677T和A1298C等位基因在德系犹太人中的独特分布。尽管C677T突变频率较高，但脊柱裂在德系犹太人中不太常见。需要进一步研究以确定C677T和A1298C突变是否对德系犹太人群的血管疾病有影响。
