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Association analyses suggest multiple interaction effects of the methylenetetrahydrofolate reductase polymorphisms on timing of menarche and natural menopause in white women.

ABSTRACT: OBJECTIVE:This study aimed to investigate whether polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene are associated with age at menarche and age at natural menopause in white women. METHODS:In a cross-sectional study, a total of 305 randomly selected unrelated white women were genotyped for six single nucleotide polymorphisms (SNPs) of the MTHFR gene (including one common replacement, rs1801133). This sample was comprehensively analyzed for the association of the SNPs with age at menarche. Then a subsample of 210 women who experienced natural menopause was analyzed for the association of the MTHFR gene with age at natural menopause. RESULTS:Duration of breast-feeding was a significant predictor of earlier natural menopause (P < 0.05). No individual SNPs were associated with either age at menarche or age at natural menopause. However, three significant (P < 0.05) SNP-SNP interaction effects (rs2066470/rs1476413, rs2066470/rs4846049, and rs17037390/rs4846049) on the onset of menarche were determined. Three haplotypes were significantly associated with age at menopause (P < 0.05). Four SNPs (rs2066470, rs17037390, rs1801133, and rs4846048) indicated significant interaction effects with various lifestyle factors on age at natural menopause. CONCLUSIONS:The results of our study suggest that the MTHFR gene may influence the onset of menarche and natural menopause. This effect is probably due to the multiple SNP-SNP and SNP-environment interactions. More independent studies are needed to further clarify the possible contribution of this gene to the timing of menarche and menopause.

SUBMITTER: Liu P

PROVIDER: S-EPMC2806497 | biostudies-literature | 2010 Jan-Feb

REPOSITORIES: biostudies-literature

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Association analyses suggest multiple interaction effects of the methylenetetrahydrofolate reductase polymorphisms on timing of menarche and natural menopause in white women.

Liu Pengyuan P Lu Yan Y Recker Robert R RR Deng Hong-Wen HW Dvornyk Volodymyr V

Menopause (New York, N.Y.) 20100101 1

<h4>Objective</h4>This study aimed to investigate whether polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene are associated with age at menarche and age at natural menopause in white women.<h4>Methods</h4>In a cross-sectional study, a total of 305 randomly selected unrelated white women were genotyped for six single nucleotide polymorphisms (SNPs) of the MTHFR gene (including one common replacement, rs1801133). This sample was comprehensively analyzed for the association of th ...[more]

PMID: 19593234

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Project description:BackgroundThe association between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and the susceptibility to cervical lesions was unclear. This study was designed to investigate their precise association using a large-scale meta-analysis.MethodsThe previous 16 studies were identified by searching PubMed, Embase and CBM databases. The crude odds ratios and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the MTHFR C677T/A1298C polymorphisms and the susceptibility to the cervical lesions. The subgroup analyses were made on the following: pathological history, geographic region, ethnicity, source of controls and source of DNA for genotyping.ResultsNeither of the polymorphisms had a significant association with the susceptibility to the cervical lesions in all genetic models. Similar results were found in the subgroup analyses. No association was found between the MTHFR C677T polymorphism and the cervical lesions in the Asia or the America populations though a significant inverse association was found in the Europe population (additive model: P = 0.006, OR = 0.83, 95% CI = 0.72-0.95; CT vs. CC: P = 0.05, OR = 0.83, 95% CI = 0.69-1.00; TT vs. CC: P = 0.05, OR = 0.73, 95% CI = 0.53-1.00). Interestingly, women with the MTHFR A1298C polymorphisms had a marginally increased susceptibility to invasive cancer (ICC) when compared with no carriers but no statistically significant difference in the dominant model (P = 0.06, OR = 1.21, 95% CI = 0.99-1.49) and AC vs. AA (P = 0.09, OR = 1.21, 95% CI = 0.97-1.51).ConclusionsThe MTHFR C677T and A1298C polymorphisms may not increase the susceptibility to cervical lesions. However, the meta-analysis reveals a negative association between the MTHFR C677T polymorphisms and the cervical lesions, especially in the European populations. The marginal association between the MTHFR A1298C polymorphisms and the susceptibility to cervical cancer requires a further study.

Project description:BackgroundAcute lymphoblastic leukemia (ALL) is the most common malignancy in children, and methotrexate (MTX) is the key drug for ALL. Studies on the relationship between High-Dose methotrexate (HD-MTX) toxicity and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genes have drawn different conclusions. This study aimed to investigate the relationship between the polymorphism of MTHFR C677T and A1298C genes and the toxicity responses of MTX.MethodsThe MTHFR C677T and A1298C genotypes of 271 children with ALL who received HD-MTX chemotherapy in southern China from September 2017 to June 2021 were analyzed, and the toxicity of HD-MTX was evaluated and analyzed according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0.ResultsThe MTHFR C677T and A1298C gene polymorphisms were not correlated with the 48-hour MTX blood concentrations (P>0.05). Unconditional logistic regression model analysis also revealed that the risk of liver function impairment [odds ratio (OR) =1.656, 95% confidence interval (CI): 1.179-2.324, P<0.05] and mucosal damage (OR =1.508, 95% CI: 1.042-2.183, P<0.05) were 1.656 and 1.508 times higher for the heterozygous mutant (CT), and homozygous mutant (TT) mutant type than for the wild-type (CC), wild-type, respectively. The risk of neutropenia and liver function impairment were 0.498 (OR =0.498, 95% CI: 0.251-0.989, P<0.05) and 6.067 (OR =6.067, 95% CI: 1.183-31.102, P<0.05) times higher in low-risk children with CT+TT mutant genotypes than in those with CC wild genotypes, respectively. Furthermore, the risk of mucosal damage was 1.906 times higher in high-risk children with the CT+TT genotype than in those with the CC genotype (OR =1.906, 95% CI: 1.033-3.518, P<0.05). The MTHFR A1298C genotypes differed in the incidence of liver function damage and gastrointestinal toxic reactions in children with ALL. Nonetheless, no increased risk of liver function impairment nor gastrointestinal reactions in children with the heterozygous mutant (AC)+CC mutation was observed.ConclusionsAdvancements in MTHFR genotype testing in children with ALL and the introduction of personalised treatments based on genotype results during HD-MTX chemotherapy will help to predict, prevent, and reduce the occurrence of adverse MTX-related toxic reactions.

Dataset Information

Association analyses suggest multiple interaction effects of the methylenetetrahydrofolate reductase polymorphisms on timing of menarche and natural menopause in white women.

Publications

Association analyses suggest multiple interaction effects of the methylenetetrahydrofolate reductase polymorphisms on timing of menarche and natural menopause in white women.

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