Polymorphisms in the CBS gene and homocysteine, folate and vitamin B₁₂ levels: Association with polymorphisms in the MTHFR and MTRR genes in Brazilian children

Abstract

Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR) and cystathionine beta-synthase (CBS) genes, involved in the intracellular metabolism of homocysteine (Hcy), can result in hyperhomocysteinemia. The objective of this study was to evaluate prevalence estimates of CBS T833C, G919A and the insertion of 68-bp (844ins68) polymorphisms and their correlation with Hcy, folate and B(12) in 220 children previously genotyped for MTHFR C677T, A1298C, and MTRR A66G. The prevalence of heterozygote children for 844ins68 was 19.5%. The T833C CBS mutation was identified in association with 844ins68 in all the carriers of the insertion. Genotyping for CBS G919A mutation showed that all the children presented the GG genotype. Analysis of Hcy, B(12) and folate, according to the combination of the different genotypes of the C677T and A1298C MTHFR, A66G MTRR, and 844ins68 CBS showed that the 677TT/1298AA/68WW genotype is associated with an increase in Hcy, when compared to the 677CC/1298AC/68WW (P = 0.033) and the 677CT/1298AA/68WW genotypes (P = 0.034). Since B(12) and folate were not different between these groups, a genetic interaction between diverse polymorphisms probably influences Hcy. Our results emphasize the role of genetic interactions in Hcy levels.

Polymorphisms in MTHFR, MS and CBS Genes and Homocysteine Levels in a Pakistani Population

“…However, these values are lower than those quoted for the Spanish and Sub Saharan populations [21] but quite comparable to those found in the Turkish, Iranian and Indian populations [22]–[24]. In the present investigation, we have also observed consistent co-segregation of these two polymorphisms in cis , which is well supported by previous observations [16], [25], [26]. The frequency of homozygous “II” insertion genotype was 0.34% which compares well with 0.2% in a Russian population [27] and 0.6% in a Thai population [28].…”

“…There have been conflicting reports about the role of CBS G919A transition in different populations. While 919A allele is highly prevalent in the Irish homocystinuria population [29], it was conspicuously absent in the populations in Italy, The Netherlands, Germany, Czech Republic, USA and Brazil [4], [26], [30]. Our reason for investigating this transition in the Pakistani population was also based on the fact that 919A allele was found to be associated with decreased risk of coronary heart disease in a Chinese population [31].…”

Relationship of the MTHFD1 (rs2236225), eNOS (rs1799983), CBS (rs2850144) and ACE (rs4343) gene polymorphisms in a population of Iranian pediatric patients with congenital heart defects

“…Both the allele of C and G at site ‐4673 was observed in both groups. Similar results in previously studies show that ‐4673C>G variant in the promoter of CBS has not been reported to be associated with many of cardiovascular diseases [23]. It also has been found that at CBS ‐4673 site, the allele frequency varies strangely in different ethnic populations.…”

Interactions among methylenetetrahydrofolate reductase (MTHFR) and cystathionine β-synthase (CBS) polymorphisms - a cross-sectional study: multiple heterozygosis as a risk factor for higher homocysteine levels and vaso-occlusive episodes

“…Since the P values in this study were >0.05 for the MTHFR C677T, MTHFR A1298C and CBS 844ins68 polymorphisms, we have no reason to reject the hypothesis that the genotype frequencies of the CBS T833C polymorphism are also in HardyWeinberg proportions, because this polymorphism segregates in cis with 844ins68 in carriers of the insertion (Franco et al, 1998;Dutta et al, 2005;Yakub et al, 2012), corroborating our results. CBS G919A showed a significant deviation from HWE, but that was expected, since in the Brazilian population it seems to be rare, and only the wild-type GG genotype has been reported (Aléssio et al, 2008).…”