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Mutant alleles with the 677C--&gt;T and 1298A--&gt;C polymorphisms of the MTHFR gene, and consequent lower methylentetrahydrofolate reductase enzyme activity, have been related to higher plasma homocysteine levels, which are associated with cardiovascular diseases. We assessed the genotype frequencies, degrees of fertility and homocysteine levels, and discuss a possible genetic selection for the gene polymorphisms studied. A total of 1777 subjects (897 women and 880 men), divided into four age groups, were genotyped by PCR and restriction fragment length polymorphism. The total homocysteine concentration in plasma was determined by fluorescence polarization immunoassay. Based on random pairs and linkage disequilibrium of the two polymorphisms, we estimated the rate of fetal non-viability according to the combinations of these two polymorphisms to be 4.63% for the group &gt;24 years old and 6.31% for the group &lt;24 years old. We detected an increased frequency of mutant alleles in the youngest age group, coincident with a generally increased folate intake by pregnant women in Spain. The genetic selection detected leads to an increase in mutated individuals, the number of whom could increase four-fold over the next 75 years. Although generally reduced in the younger age groups, the homocysteine plasma levels were shown to increase in individuals according to the number of mutations, especially those of the 677T allele.

Implications on human fertility of the 677C->T and 1298A->C polymorphisms of the MTHFR gene: consequences of a possible genetic selection