Methionine synthase A2756G and reduced folate carrier1 A80G gene polymorphisms as maternal risk factors for Down syndrome in Egypt

Background: Polymorphisms of genes encoding enzymes involved in folate metabolism have long been hypothesized to be maternal risk factors for Down syndrome, however, results are conflicting and inconclusive

Aim of the study: To analyze the effect of methionine synthase [MTR] A2756G, and reduced folate carrier [RFC1] A80G gene polymorphisms on the maternal risk for DS

Patients: This study was conducted in the Medical Genetics Center, Ain-Shams University hospitals, on a total of 170 mothers of children, diagnosed with Down syndrome, who were attending the center. Eighty-five control mothers were also enrolled in the study

Methods: Genotype analyses were performed using PCR-RFLP to detect RFC1A80G and MTRA2756G gene polymorphisms in all case and control mothers

Results: Comparing RFC1A80G genotype frequency between both groups revealed, that the frequency of the AA genotype in case mothers [94.11%] is highly significantly [p< 0.001] greater than its frequency in control mothers [74.11%], with no significant difference between the two groups regarding GG genotype. Comparing RFC1 A80G allele frequency between the two groups revealed a high frequency of the A allele among case mothers [94.11%], which showed a highly statistically significant difference [p<0.001] from the control group [55.29%], meanwhile the G allele showed a low frequency of 5.88% in DS mothers compared to 22.35% in the control mothers, with a highly statistically significant difference [p<0.001] between the two groups. Regarding MTRA2756G polymorphism, it was found that the AA genotype predominated in the control group [65.88%] with a highly statistically significant difference [p< 0.001] from case mothers group [5.88%]. Comparing MTR allele frequency between the two groups revealed predominance of the G allele among mothers of DS children [76.47%]

Conclusion: Current results provide strong evidence that the MTRA2756G, and RFC1 80 A genotypes could be considered as maternal risk factors for DS in Egyptian mothers

Genetic variation in genes involved in folate and drug metabolism in a south Indian population.

BACKGROUND: Genetic variations represented as single nucleotide polymorphisms (SNPs) vary across the world population. This genetic polymorphism (such as SNPs) plays an important role in pharmacogenomics. SNPs that affects cellular metabolism, by altering the enzyme activity, have an important role in therapeutic outcome. Allele frequencies in number of clinically relevant SNPs within south Indian populations are not yet known. Hence, we genotyped randomly selected unrelated south Indian subjects from different locations of south India representing the heterogeneous ethnic background of the population. MATERIALS AND METHODS: Common variants of MTHFD1, TYMS, SHMT1, MTR, MTRR, CBS and SULT1A1 gene polymorphisms were screened from healthy unrelated south Indian volunteers. Genotypes were determined using RFLP analysis of polymerase chain reaction-amplified products and confirmed by DNA sequencing. Chi-square test was performed to test for deviation from the Hardy-Weinberg equilibrium for each locus. RESULTS: Gene allele frequency for several polymorphisms in our study differed significantly between the populations of other nations reported for several of the SNPs. These results demonstrate that the populations in different geographic regions may have widely varying genetic allele frequencies for clinically relevant SNPs. CONCLUSION: The present study reports, for the first time, the frequency distribution of MTHFD1, TYMS, SHMT1, MTR, MTRR, CBS and SULTIA1 gene polymorphisms in a south Indian population. Population-specific genetic polymorphism studies will help in practicing pharmacogenomic principles in the clinics.

Homozygous VN (677C to T) and d/D (2756G to A) variants in the methylenetetrahydrofolate and methionine synthase genes in a case of hyperhomocysteinemia with stroke at young age

Hyperhomocysteinemia is known to be associated with an increased risk of myocardial infarction, stroke, peripheral arterial disease, and venous thrombosis. Gene polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) may account for reduced enzyme activity and hyperhomocysteinemia. A recent study has documented evidence of polygenic regulation of plasma homocyteine. We report here on a case of occlusive stroke at young age and hyperhomocysteinemia with homozygous VN (677C to T) variant in the MTHFR gene as well as homozygous D/D (2756G to A) variant in the MS gene.