A second common variant in the methylenetetrahydrofolate reductase (MTHFR) gene and its relationship to MTHFR enzyme activity, homocysteine, and cardiovascular disease risk

Therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) is a malignancy occurring after exposure to chemotherapy and/or radiotherapy. Polymorphisms involved in chemotherapy/radiotherapy response genes could be related to an increased risk of developing this neoplasia. We have studied 11 polymorphisms in genes of drug detoxification pathways (NQO1, glutathione S-transferase pi) and DNA repair xeroderma pigmentosum, complementation group (3) (XPC(3), X-ray repair cross complementing protein (1)), Nijmegen breakage syndrome (1), excision repair cross-complementing rodent repair deficiency, complementation group (5) and X-ray repair cross complementing protein (3) and in the methylene tetrahydrofolate reductase gene (MTHFR(2), 677C4T, 1298A4C), involved in DNA synthesis. The analyzed groups were a t-MDS/ AML patients group (n ¼ 81) and a matched control group (n ¼ 64) treated similarly, and they did not develop t-MDS/AML. We found no significant differences when the groups were compared globally. However, when analysis was carried out according to the primary neoplasia involved, a significant association was observed between the MTHFR haplotype (single nucleotide polymorphisms 677 and 1298) and the risk of developing t-MDS/AML in the breast cancer patients group (P ¼ 0.016) and cyclophosphamide-treated hematological disease group (P ¼ 0.005). Risk haplotype was different for each case, corresponding to the 677T1298A haplotype after breast cancer treatment and the 677C1298C haplotype after hematological malignancy treatment. We postulate that such differences are related to variations in chemotherapy schemes between hematological and breast cancers and their differential interaction with the MTHFR route.

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“…29 On the other hand, the 1298C allele (CC haplotype) does not present thermolability, 27 and has no effect on homocysteine levels. 30 …”

Section: Description Of Mthfr Haplotypes and Their Biological Differementioning

confidence: 99%

Role of MTHFR (677, 1298) haplotype in the risk of developing secondary leukemia after treatment of breast cancer and hematological malignancies

et al. 2007

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“…The previous research had reported that the carriers of the A1298C variant allele could increase the serum folate levels, possibly influencing cancer risk susceptivity (Lievers et al, 2001;ParleMcDermott et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

No Association Between MTHFR A1298C Gene Polymorphism and Head and Neck Cancer Risk: A Meta-analysis Based on 9,952 Subjects

Niu

Shen²,

Li³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Objective: Findings for associations between the methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and head and neck cancer risk have been conflicting. We therefore performed a meta-analysis to derive a more precise relationship. Methods: Ten published case-control studies were collected and odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between MTHFR A1298C polymorphism and head and neck cancer risk. Sensitivity analysis and publication bias assessment also were performed to guarantee the statistical power. Results: Overall, no significant association between MTHFR A1298C polymorphism and head and neck cancer risk was found in this meta-analysis (C vs.

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“…The C677T polymorphism is located in exon 4 and causes a change of an alanine for a valine at codon 222, which is associated with increased thermolability and decreased MTHFR enzyme activity of up to 70%, resulting in moderate hyperhomocysteinemia in TT homozygous individuals Weisberg et al, 1998;Song et al, 2001b). The A1298C polymorphism is located in exon 7 and results in a substitution of glutamate by alanine at codon 429, which also decreases the MTHFR enzyme activity, although to a lesser degree than the C677T polymorphism (Weisberg et al, 1998;Lievers et al, 2001;Chen et al, 2002). Individuals heterozygous for both polymorphisms have MTHFR enzyme activity comparable to that observed in individuals homozygous for the 677TT genotype, resulting in an increase of homocysteine and a decrease in plasma folate levels (van der Put et al, 1998;Weisberg et al, 1998;Friedman et al, 1999;Friso et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Ethnic variation of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate-reductase (MTHFR) gene in southwestern Mexico

Antonio-Véjar¹,

Moral-Hernández²,

Alarcón-Romero³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. In this study, we examined the distribution of genotype and allele frequencies of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate-reductase gene (MTHFR) in two ethnic groups in the State of Guerrero, Mexico, which were compared with those of the Mestizo population of the region. A comparative study was conducted on 455 women from two ethnic groups and a group of Mestizo women of the State of Guerrero, Mexico: 135 Nahuas, 124 Mixtecas, and 196 Mestizas. Genotyping of both polymorphisms were performed by using polymerase chain reaction-restriction fragment length polymorphism methods. We found that the 677TT genotype was more frequent in Nahua and Mixteca women compared to Mestiza women (P = 0.008), and the most prevalent genotype in both ethnic groups was the 1298AA genotype (P < 0.001). We also compared Ethnic variation of MTHFR polymorphisms in Mexico the 677T allele frequency obtained from the groups studied with the frequencies reported in other ethnic groups of Mexico (Huichol, Tarahumara, and Purepecha). There were significant differences between the three ethnic groups compared to Nahuas (Huicholes, P = 0.004; Tarahumaras, P < 0.001; Purepechas, P = 0.042). Our results indicated significant differences in the frequencies of the C677T and A1298C polymorphisms between the two ethnic groups and the Mestizo population of the State of Guerrero. In addition, we found strong differences with other ethnic groups in Mexico. These results could be useful for future studies investigating diseases related to folate metabolism, and could help the government to design specific nutrition programs for different ethnic groups.

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A second common variant in the methylenetetrahydrofolate reductase (MTHFR) gene and its relationship to MTHFR enzyme activity, homocysteine, and cardiovascular disease risk

Cited by 161 publications

References 27 publications

Role of MTHFR (677, 1298) haplotype in the risk of developing secondary leukemia after treatment of breast cancer and hematological malignancies

Role of MTHFR (677, 1298) haplotype in the risk of developing secondary leukemia after treatment of breast cancer and hematological malignancies

No Association Between MTHFR A1298C Gene Polymorphism and Head and Neck Cancer Risk: A Meta-analysis Based on 9,952 Subjects

Ethnic variation of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate-reductase (MTHFR) gene in southwestern Mexico

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