Large differences in the proportion of people with reduced MTHFR Enzymatic activity in Eurasia: allele and haplotype distribution of MTHFR-C677T and MTHFR-A1298C polymorphisms in Spain and Siberia

Abstract

Adequate levels of folate are crucial for human development. MTHFR (Methylene tetrahydrofolate reductase) is involved in the metabolism of folic acid and other B vitamins. The aim of this work is to examine the allele frequency and haplotype distribution of MTHFR-C677T and MTHFR-A1298C polymorphisms in two independent samples (North- East Spanish and North-Western Siberia). The degree of population differentiation and signatures of positive selection were also examined in 18 world populations. The samples comprised 623 Spanish individuals and 172 Ob-Ugric people (Khanty and Mansi). The Spanish sample showed 44% individuals with 30% reduced enzyme activity, and 16% people with 70% reduced activity; whereas the Khanty sample revealed only 3% people with 70% reduced activity. In the 18 populations screened, we found significant South to North clines for SNPs and haplotypes. Overall, we failed to detect any traces of positive selection. The high frequency of people with reduced MTHFR enzyme activity in Spain highlights the need for diets rich in folate and folic acid supplementation in some groups. The low frequency of individuals with reduced enzymatic activity among the Khanty together with their traditional diet indicates a protective combination against pathologies related to folic acid deficiencies.