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Mutant alleles with the 677C-->T and 1298A-->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 >24 years old and 6.31% for the group <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.

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Significant correlations were found between Ang I and Ang II as well as between Ang II and Ang-(1-7) in the different study group distributions. No correlation was found between levels of Ang I and Ang-(1-7). Certain genotypes exert an influence on angiotensin peptide plasma levels which can only be seen when the population is divided according to gender.

BACKGROUND Polymorphisms C677T and A1298C of the MTHFR gene have been implicated in fetal viability. In this study, we determined the allele and genotype frequencies of these polymorphisms in different populations, including spontaneous abortion (SA) fetal tissues, with the objective of evaluating their impact on fetal viability. METHODS 342 samples of fetal tissues, selected from SA occurring during the 1980s, 230 samples from subjects born in the 1980s and a third set of samples from 204 subjects born in the 1950s, were genotyped by using TaqMan probes. RESULTS The wild CC genotype of the C677T polymorphism showed a strong protective effect against abortion (0.03 in SA versus 0.47 in 1950s and 0.43 in 1980s) (P < 0.0001). Genotypes of three mutations in the combinations of polymorphisms for C677T and A1298C showed a very low frequency in the living population; however, the three mutations genotypes were over expressed in the SA group (0.02 in 1950s; 0.03 in 1980s and 0.17 in SA) (P < 0.0001). Samples with four mutations (n = 2) were found only in the SA group. CONCLUSIONS There is no linkage disequilibrium between C667T and A1298C polymorphisms. Fetal viability is directly related to the CC genotype as a protector while the three and four mutation MTHFR genotypes appear to be a determinant on fetal non-viability and SA.

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Background: The prevalence of genotypes of the 677C>T polymorphism for the MTHFR gene varies among humans. In previous studies, we found changes in the genotypic frequencies of this polymorphism in populations of different ages, suggesting that this could be caused by an increase in the intake of folate and multivitamins by women during the periconceptional period. The aim was to analyze changes in the allelic frequencies of this polymorphism in a Spanish population, including samples from spontaneous abortions (SA).

We have studied the role of three polymorphic genes of the renin-angiotensin system (RAS) as independent risk factors for myocardial infarction (MI) and their correlation with three of the major coronary risk factors: serum cholesterol (CH), hypertension (HT) and smoking (SM). A population of 392 men was genotyped for the M235T polymorphism of the angiotensinogen (AGT) gene, the insertion/deletion of the angiotensin-converting enzyme (ACE) and the all66c of the angiotensin-II type 1 receptor (AT1R), by means of polymerase chain reaction (PCR) and restriction enzyme analysis. It was observed that the T allele frequency increased significantly in the MI with HT, CH, and SM subgroup (0.58 vs 0.31) (p<0.01). In contrast, the M allele frequency was higher in the MI without HT, CH, and SM (0.69 vs 0.42) (p<0.01). A strong association between the MM genotype and MI (p<0.001, odds ratio=4.29, confidence interval=1.95-9.42) was found when age-matched MM control subjects were compared to MI individuals with none of the other known major coronary risk factors. Futhermore, subjects with the MM genotype showed a significantly higher plasma renin activity (PRA) profile than those with the TT genotype (p<0.001). It can be concluded that the M allele is an independent risk factor for MI and the T allele modified the risk when other major risk factors are present.