<scp>MTHFR</scp> gene C677T and A1298C variants are associated with <scp>FMF</scp> risk in a Turkish cohort

Nursal, Ayşe Feyda; Kaya, Süheyla Uzun; Sezer, Özlem; Karakuş, Nevin; Yığıt, Serbülent

doi:10.1002/jcla.22259

Cited by 5 publications

(2 citation statements)

References 33 publications

(36 reference statements)

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“…Familial Mediterranean Fever, recessive hereditary auto inflammatory disease, showed association with T677T and A1298C [57].…”

Section: Familial Mediterranean Fevermentioning

confidence: 96%

Folate Metabolism. Polymorphisms of Methylentetrahydrofolate Reductase. Concurrent Factor in Pathogenic Effects

Voyer

2023

AJBSR

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Vitamin B9, folate in its natural form is present in vegetables, fruits and organ meats. The function of folate is to act in processes of transfer one carbon compounds, methylation on nucleotides, amino acids and phospholipids, processes of vital importance for cell division, synthesis of nucleic acids, amino acids and methionine from homocysteine1. Folic acid is the synthetic form most used as a supplement to compensate low intakes of folate but has not normal biological actions if it is not converted to 5-methylenetetrahydrofolate, by the enzyme methylenetetrahydrofolate reductase. This enzyme may presents polymorphism due to mutation with biotypes of varied activity. The most commonly present, C677C and A1298A, has full activity, but C677T and T677T and A1298C and C1298C with decreased activity between 30 and 70 %, can cause metabolic alterations such as hyperhomocysteinemia and DNA hypomethylation with increased risk for chromosomal abnormalities and various pathological conditions, as neural tube development disorders, early recurrent pregnancy losses, Down syndrome, cleft lip and/or palate, limb reduction, cancer, mediterranean familial fever, polycystic ovarian syndrome and neurological or cardiovascular diseases. Faced with a history of these disorders and the presence of the aforementioned enzyme biotypes, the replacement of folic acid by L 5-methylenetetrahydrofolate supplied together with vitamin B12, B2, and B6 may reduce the risk. Beside this, with excessive intakes of folic acid, especially when low activity of the enzyme is preset, high levels in the blood can be produced, with consequently higher risk of various health problems. To avoid this, recommended intakes of folic acid should not be exceeded.

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“…Familial Mediterranean Fever, recessive hereditary auto inflammatory disease, showed association with T677T and A1298C [57].…”

Section: Familial Mediterranean Fevermentioning

confidence: 96%

Folate Metabolism. Polymorphisms of Methylentetrahydrofolate Reductase. Concurrent Factor in Pathogenic Effects

Voyer

2023

AJBSR

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“…The 677C-T gene mutation is located in exon 4 of the catalytic activity of the N-terminal region, where cytosine is replaced by thymine, and the corresponding protein is changed from alanine (Ala) to valine (Val). The 1298A-C mutation is located in the C-terminal regulatory region of exon 7, where adenosine mutates to cytosine, causing the glutamate (Glu) encoding to be replaced by alanine (Ala) (Weisberg et al, 2001;Chen et al, 2009;Nursal et al, 2018). Globally, the ethnic and geographic distribution of these two loci are significantly different.…”

Section: Introductionmentioning

confidence: 99%

Association Between MTHFR Polymorphisms and the Risk of Essential Hypertension: An Updated Meta-analysis

et al. 2021

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Background: Since the 1990s, there have been a lot of research on single-nucleotide polymorphism (SNP) and different diseases, including many studies on 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism and essential hypertension (EH). Nevertheless, their conclusions were controversial. So far, six previous meta-analyses discussed the internal relationship between the MTHFR polymorphism and EH, respectively. However, they did not evaluate the credibility of the positive associations. To build on previous meta-analyses, we updated the literature by including previously included papers as well as nine new articles, improved the inclusion criteria by also considering the quality of the papers, and applied new statistical techniques to assess the observed associations. Objectives: This study aims to explore the degree of risk correlation between two MTHFR polymorphisms and EH. Methods: PubMed, EMBASE, the Cochrane Library, CNKI, and Wan Fang electronic databases were searched to identify relevant studies. We evaluated the relation between the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms and EH by calculating the odds ratios (OR) as well as 95% confidence intervals (CI). Here we used subgroup analysis, sensitivity analysis, cumulative meta-analysis, assessment of publication bias, meta-regression meta, False-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and Venice criterion. Results: Overall, harboring the variant of MTHFR C677T was associated with an increased risk of EH in the overall populations, East Asians, Southeast Asians, South Asians, Caucasians/Europeans, and Africans. After the sensitivity analysis, positive results were found only in the overall population (TT vs. CC: OR = 1.14, 95% CI: 1.00–1.30, Ph = 0.032, I2 = 39.8%; TT + TC vs. CC: OR = 1.15, 95% CI: 1.01–1.29, Ph = 0.040, I2 = 38.1%; T vs. C: OR = 1.14, 95% CI: 1.04–1.25, Ph = 0.005, I2 = 50.2%) and Asian population (TC vs. CC: OR = 1.14, 95% CI: 1.01–1.28, Ph = 0.265, I2 = 16.8%; TT + TC vs. CC: OR = 1.17, 95% CI: 1.04–1.30, Ph = 0.105, I2 = 32.9%; T vs. C: OR = 1.10, 95% CI: 1.02–1.19, Ph = 0.018, I2 = 48.6%). However, after further statistical assessment by FPRP, BFDP, and Venice criteria, the positive associations reported here could be deemed to be false-positives and present only weak evidence for a causal relationship. In addition, when we performed pooled analysis and sensitivity analysis on MTHFR A1298C; all the results were negative. Conclusion: The positive relationships between MTHFR C677T and A1298C polymorphisms with the susceptibility to present with hypertension were not robust enough to withstand statistical interrogation by FPRP, BFDP, and Venice criteria. Therefore, these SNPs are probably not important in EH etiology.

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Impact of pregnancy on inborn errors of metabolism

Wilcox

2018

Rev Endocr Metab Disord

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Once based mainly in paediatrics, inborn errors of metabolism (IEM), or inherited metabolic disorders (IMD) represent a growing adult medicine specialty. Individually rare these conditions have currently, a collective estimated prevalence of >1:800. Diagnosis has improved through expanded newborn screening programs, identification of potentially affected family members and greater awareness of symptomatic presentations in adolescence and in adulthood. Better survival and reduced mortality from previously lethal and debilitating conditions means greater numbers transition to adulthood. Pregnancy, once contraindicated for many, may represent a challenging but successful outcome. Successful pregnancies are now reported in a wide range of IEM. Significant challenges remain, given the biological stresses of pregnancy, parturition and the puerperium. Known diagnoses allow preventive and pre-emptive management. Unrecognized metabolic disorders especially, remain a preventable cause of maternal and neonatal mortality and morbidity. Increased awareness of these conditions amongst all clinicians is essential to expedite diagnosis and manage appropriately. This review aims to describe normal adaptations to pregnancy and discuss how various types of IEM may be affected. Relevant translational research and clinical experience will be reviewed with practical management aspects cited. Based on current literature, the impact of maternal IEM on mother and/or foetus, as well as how foetal IEM may affect the mother, will be considered. Insights gained from these rare disorders to more common conditions will be explored. Gaps in the literature, unanswered questions and steps to enhance further knowledge and systematically capture experience, such as establishment of an IEM-pregnancy registry, will be summarized.

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MTHFR gene C677T and A1298C variants are associated with FMF risk in a Turkish cohort

Abstract: Our findings clearly showed there was an association the MTHFR C677T/A1298C variants and susceptibility to FMF in the Turkish sample.

Cited by 5 publications

References 33 publications

Folate Metabolism. Polymorphisms of Methylentetrahydrofolate Reductase. Concurrent Factor in Pathogenic Effects

Folate Metabolism. Polymorphisms of Methylentetrahydrofolate Reductase. Concurrent Factor in Pathogenic Effects

Association Between MTHFR Polymorphisms and the Risk of Essential Hypertension: An Updated Meta-analysis

Impact of pregnancy on inborn errors of metabolism

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