Methylenetetrahydrofolate reductase (MTHFR): The incidence of mutations C677T and A1298C in the Ashkenazi Jewish population

The polymorphic mutation C677T in the gene of MTHFR is considered a risk mu tation for spina bifida and vascular disease. Another common mutation on th e 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 HinfI digestion, and mutatio n A1298C by PCR and Mbo II digestion. A total of 310 alleles was examined f or 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 compare d 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 counterpart s 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 significa nt, P < 0.031. No individuals were homozygous for both mutations or were fo und to be homozygous for one mutation with heterozygosity of the other muta tion, and that the C677T and the A1298C alleles did not occur in cis positi on. This study shows a unique distribution of C677T and the A1298C alleles among the Ashkenazi Jews. In spite of high frequency of C677T mutation, spi na bifida is less common among Ashkenazi Jews. Further studies are needed t o establish whether the C677T and the A1298C mutations have an impact on va scular disease in the Ashkenazi Jewish population. Am, J, Med, Genet, 86:38 0-384, 1999. (C) 1999 Wiley-Liss, Inc.