The MTHFR 1298CC and 677TT genotypes have opposite associations with red cell folate levels

Parle‐McDermott, Anne; Mills, James L.; Molloy, Anne M.; Carroll, Nicola; Kirke, Peadar N.; Cox, Christopher; Conley, Mary; Pangilinan, Faith; Brody, Lawrence C.; Scott, John M.

doi:10.1016/j.ymgme.2006.02.011

Cited by 47 publications

(35 citation statements)

References 25 publications

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“…The biochemical effect of c.1298A>C is unclear with initial in vitro studies, suggesting reduced MTHFR activity in the c.1298 variant allele, and subsequent studies showing minimal effect on folate status (15,60). More recently, the c.1298 C allele has been reported to result in elevated red cell folate as it converts 5,10-MTHF to the more stable 5-methyltetrahydrofolate at an accelerated rate, which may in part explain our results (61). It is also possible that the observed association between c.1298 genotype and homocysteine is a consequence of an indirect association between c.677 genotype, and homocysteine because of the strong linkage disequilibrium between the two SNPs (62).…”

Section: Discussionmentioning

confidence: 70%

Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene Polymorphisms and Toxicity to Capecitabine in Advanced Colorectal Cancer Patients

Sharma

Hoskins

Rivory

et al. 2008

Clinical Cancer Research

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Purpose: To evaluate the effect of thymidylate synthase (TYMS) and methylenetetrahydrofolate reductase (MTHFR) genotypes on toxicity in patients treated with capecitabine for advanced colorectal cancer and to determine the effect of these polymorphisms on the pretreatment levels of serum folate and plasma homocysteine. Experimental Design: Fifty-four patients with a diagnosis of metastatic colorectal cancer were treated with fixed-dose capecitabine. Germ line DNA from patients was genotyped for TYMS

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Section: Discussionmentioning

confidence: 70%

Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene Polymorphisms and Toxicity to Capecitabine in Advanced Colorectal Cancer Patients

Sharma

Hoskins

Rivory

et al. 2008

Clinical Cancer Research

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“…The C-to-T transition at nucleotide 677 in exon 4 is a point mutation that converts a cytosine (C) to a thymine (T), resulting in an alanine-to-valine mutation, which can affect the thermal stability and reduce the activity of MTHFR. The MTHFR gene A1298C (rs1801131) mutation in exon 7, a glutamate-to-alanine substitution at codon 429 (E429A), can increase serum folate levels (Parle-McDermott et al, 2006). In adult male mice, MTHFR levels are highest in the testis, and in Mthfr gene knockout mice, the MTHFR deficiency resulting in abnormal spermatogenesis and infertility in males suggests an important role for MTHFR in spermatogenesis (Kelly et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Association between C677T and A1298C polymorphisms of the MTHFR gene and risk of male infertility: a meta-analysis

Yang

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Published studies on the association between the C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene and male infertility risk are controversial. To obtain a more precise evaluation, we performed a meta-analysis based on published case-control studies. We conducted an electronic search of PubMed, EMBASE, the Cochrane Library, the Web of Science, and the China Knowledge Resource Integrated Database for papers on MTHFR gene C677T and A1298C polymorphisms and male infertility risk. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were used to assess the strength of association in homozygote, heterozygote, dominant, recessive, and additive models. Statistical heterogeneity, test of publication bias, and sensitivity analysis were carried out using the STATA software (Version 13.0). Overall, 21 studies of C677T (4505 cases and 4024 controls) and 13 studies of A1298C (2785 cases and 3094 controls) were included in this meta-analysis. For C677T, the homozygote comparison results were OR = 1.629, 95%CI (1.215-2.184), and the recessive model results were OR = 1.462 (1.155-1.850). For A1298C, the homozygote comparison results were OR = 1.289 (1.029-1.616), and the recessive model results were OR = 1.288 (1.034-1.604). In conclusion, the current meta-analysis showed that the MTHFR C677T polymorphism was associated with a significantly increased male infertility risk in the Asian and overall populations, but not in the Caucasian population, and there was a significant association between the A1298C polymorphism and male infertility risk in the Asian, Caucasian, and overall groups.

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“…[13][14][15] In relation to cancer, polymorphisms in other genes in this pathway have been studied less frequently. [16][17][18][19] However, like MTHFR, variation in these genes can result in elevated levels of plasma homocysteine, presumably because of decreased enzyme activity.…”

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confidence: 99%

Polymorphisms in one‐carbon metabolism and trans‐sulfuration pathway genes and susceptibility to bladder cancer

Moore

Malats

Rothman

et al. 2007

Intl Journal of Cancer

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We have previously reported significant inverse associations between bladder cancer risk and dietary intake of vitamins B2, B6, B12, folate and protein in a hospital-based bladder cancer case-control study conducted in Spain (1,150 cases;1,149 controls). Because these dietary factors are involved in the one-carbon metabolism pathway, we evaluated associations between bladder cancer risk and 33 single nucleotide polymorphisms (SNPs) in 8 genes (CBS, CTH, MTHFR, MTR, MTRR, SHMT1, SLC19A1 and TYMS) and interactions with dietary variables involved in this pathway. Two SNPs in the CTH gene were significantly associated with bladder cancer risk. OR (95% CI) for heterozygous and the homozygous variants compared to homozygous wild-type individuals were: 1.37 (1.04-1.80) IVS3-66 A > C and 1.22 (1.02-1.45) IVS10-430 C > T. Because the CTH gene is important for glutathione synthesis, we examined interactions with the GSTM1 gene, which codes for glutathione S-transferase lu. Increased risk for individuals with the IVS10-430 CT or TT genotype was limited to those with the GSTM1 null genotype (p-interaction 5 0.02). No other SNPs were associated with risk of bladder cancer. These findings suggest that common genetic variants in the one-carbon pathway may not play an important role in the etiology of bladder cancer. However, our results provide some evidence that variation in glutathione synthesis may contribute to risk, particularly among individuals who carry a deletion in GSTM1. Additional work is needed to comprehensively evaluate genomic variation in CTH and related genes in the trans-sulfuration pathway and bladder cancer risk. ' 2007 Wiley-Liss, Inc.Key words: bladder cancer; folate metabolism; one-carbon metabolism; GSTM1; CTH; genetic susceptibility Epidemiological studies have shown associations between low folate intake and increased cancer risk.1-5 Recently, we observed inverse associations for several B vitamins including folate, which are involved in one-carbon metabolism and bladder cancer risk. 6 Although epidemiologic evidence strongly supports an association between low folate and higher risk of colon cancer, the association with bladder cancer has not been observed. [7][8][9][10][11] Efficient functioning of the one-carbon metabolism pathway is dependent upon dietary intake of folate, B vitamins as co-factors, and methionine, an essential amino acid that is derived from protein intake. This pathway is also fundamental to many cellular processes including genomic DNA methylation and nucleotide synthesis and repair.12 Among several genetic polymorphisms in the folate metabolic pathway characterized thus far, 2 SNPs in the methylene tetrahydrofolate reductase (MTHFR) gene, A222V and E429A, have received the most attention and may be associated with decreased enzyme function. [13][14][15] In relation to cancer, polymorphisms in other genes in this pathway have been studied less frequently. [16][17][18][19] However, like MTHFR, variation in these genes can result in elevated levels of plasma homocysteine, presum...

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The MTHFR 1298CC and 677TT genotypes have opposite associations with red cell folate levels

Cited by 47 publications

References 25 publications

Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene Polymorphisms and Toxicity to Capecitabine in Advanced Colorectal Cancer Patients

Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene Polymorphisms and Toxicity to Capecitabine in Advanced Colorectal Cancer Patients

Association between C677T and A1298C polymorphisms of the MTHFR gene and risk of male infertility: a meta-analysis

Polymorphisms in one‐carbon metabolism and trans‐sulfuration pathway genes and susceptibility to bladder cancer

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