Methylenetetrahydrofolate Reductase C677T Gene Polymorphism as a Risk Factor for Hypertension in a Rural Population

Hypertension remains a public health burden despite advances in its management. Hence, the search for further risk stratification tools and prevention and new treatment approaches continues. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with hypertension. Interestingly, riboflavin, as a cofactor of MTHFR, may control blood pressure in patients with mutant MTHFR variants. These double benefits of a risk stratification tool and treatment approach make it interesting. Because this polymorphism depends on ethnicity and geographic region, we aimed to determine the association between MTHFR C677T gene polymorphism and hypertension in a rural Indonesian-Sundanese population. This population-based case-control study included 213 hypertensive subjects and 202 nonhypertensive subjects as controls. The TaqMan assay was used to determine the MTHFR C677T genotypes. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the risk of association. There was a significant difference in MTHFR C677T allele frequencies between the hypertensive and control groups (62.9% CC, 34.3% CT, 2.8% TT vs. 77.7% CC, 20.8% CT, 1.5% TT; p=0.004) and between mutant (TT and CT) and wild-type genotypes (CC) (p=0.001). The mutant genotype was associated with a risk of hypertension (OR 2.1; 95% CI 1.3–3.5) when adjusted for age, body mass index, waist circumference, and diabetes mellitus. The mutant of the MTHFR C677T gene increases the risk of hypertension in rural Indonesian-Sundanese population. These findings may be used in future studies to evaluate the effect of riboflavin supplementation in this population.

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METHYLENETETRAHYDROFOLATE REDUCTASE C677T GENE POLYMORPHISM AND PROSTATE CANCER RISK

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i5.24390 ◽

2018 ◽

Vol 11 (5) ◽

pp. 387

Author(s):

Samah Tellouche-bouhouhou ◽

Djalila Chellat-rezgoune ◽

Noureddine Abadi ◽

Dalila Satta ◽

Abderrezak Dahdouh

Keyword(s):

Prostate Cancer ◽

Methylenetetrahydrofolate Reductase ◽

Cancer Susceptibility ◽

Prostate Cancer Risk ◽

Mthfr C677t ◽

Mthfr Gene ◽

Single Nucleotide ◽

Mthfr C677t Polymorphism ◽

Increased Risk ◽

Significant Difference

Objective: The single nucleotide polymorphism C677T of the methylenetetrahydrofolate reductase (MTHFR) gene encodes a thermolabile enzyme. This polymorphism was found to be implicated in cancer susceptibility. In this study, we analyzed the distribution of the MTHFR C677T polymorphism in two cohorts; patients and controls native of East of Algeria to explore the possible association between this polymorphism and prostate cancer susceptibility.Methods: Our examination has been conducted in 98 cases and 98 healthy controls. Genotyping was realized by polymerase chain reaction-restriction fragment length polymorphism method.Results: Compared with CC homozygous, the CT heterozygous was found to have a significantly increased risk of prostate cancer (p=0.04; odds ratio [OR]=2.01, 95% confidence interval [CI]: 1.02–3.95). However, no statistically significant difference was observed concerning the TT homozygous (p=0.74; OR=1.25, 95% CI: 0.51–3.04).Conclusion: Our results indicate that the genotype CT is a risk factor for prostate cancer in East of Algeria.

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Methylenetetrahydrofolate Reductase Gene Polymorphism (C677T) as a Risk Factor for Arterial Thrombosis in Georgian Patients

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029618757345 ◽

2018 ◽

Vol 24 (7) ◽

pp. 1061-1066 ◽

Cited By ~ 2

Author(s):

Sopio Garakanidze ◽

Elísio Costa ◽

Elsa Bronze-Rocha ◽

Alice Santos-Silva ◽

Giorgi Nikolaishvili ◽

...

Keyword(s):

Risk Factor ◽

Gene Polymorphism ◽

Patient Group ◽

High Frequency ◽

Arterial Thrombosis ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

C677t Polymorphism ◽

Mthfr C677t Polymorphism ◽

Mthfr Gene Polymorphism

Methylenetetrahydrofolate reductase ( MTHFR) gene polymorphism (C677T)] is a well-recognized genetic risk factor for venous thrombosis; however, its association with arterial thrombosis is still under debate. Herein, we evaluated the prevalence of MTHFR C677T polymorphism in Georgian patients in comparison with healthy individuals and its association with arterial thrombosis. We enrolled 214 participants: 101 with arterial thrombosis (71.3% males; mean age: 66.3 ± 12.1 years) and 113 controls (67.3% males; mean age: 56.6 ± 11.3 years). Genomic DNA was extracted from dry blood spot on Whatman filter paper. Polymerase chain reaction was performed to determine MTHFR C677T polymorphism. Frequency of C677T allele polymorphism in controls was 21.2%, which corresponded to heterozygous and homozygous stage frequencies of 35.4% and 3.5%, respectively. In patient group, an allelic frequency of 33.2% was found, which corresponded to the presence of 48.5% of heterozygous and 8.9% of homozygous individuals. Comparing the frequency of mutated alleles between the 2 groups, a significantly high frequency of mutated alleles was found in patient group ( P < .05). In conclusion, high frequency of MTHFR C677T polymorphism found in arterial thrombosis patient group suggests that this polymorphism might increase the risk of arterial thrombosis in Georgian patients.

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Methylenetetrahydrofolate Reductase Polymorphisms and Pregnancy Outcome

Geburtshilfe und Frauenheilkunde ◽

10.1055/a-0664-8237 ◽

2018 ◽

Vol 78 (09) ◽

pp. 871-878 ◽

Cited By ~ 9

Author(s):

Mert Turgal ◽

Fatma Gumruk ◽

Ergun Karaagaoglu ◽

Mehmet Beksac

Keyword(s):

Pregnancy Outcome ◽

Pregnancy Outcomes ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Study Groups ◽

Mthfr Polymorphism ◽

Mthfr C677t Polymorphism ◽

Mthfr Polymorphisms ◽

Group I ◽

Significant Difference

Abstract Introduction Aim of the study was to evaluate the effect of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on pregnancy outcome. Materials and Methods A total of 617 pregnancies of women who were investigated for MTHFR C677T and A1298C polymorphisms prior to pregnancy were included in the study. Cases were classified into “homozygous polymorphisms” (Group I), “heterozygous polymorphisms” (Group II), and patients without polymorphisms who functioned as controls (Group III). Patients with polymorphisms were assigned to a specific protocol at least 3 months before becoming pregnant. Administration of low molecular weight heparin (LMWH) was started very early during pregnancy. The Beksac Obstetrics Index (BOI) was used to estimate the obstetric risk levels for the different groups. Results We found that the early pregnancy loss (EPL) rate increased as MTHFR polymorphism complexity increased and that the early EPL rate was significantly higher in patients with MTHFR C677T polymorphism compared to patients with MTHFR A1298C polymorphism (p = 0.039). There were significant differences between the previous pregnancies of the patients in the 3 study groups in terms of perinatal complications and EPLs (p = 0.003 and p = 0.019). The BOI decreased as the severity of polymorphisms increased. An association between MTHFR polymorphisms and congenital malformations and chromosomal abnormalities was observed. We could not demonstrate any statistically significant difference between study groups when the 3 groups were compared with regard to the pregnancy outcomes under specific management protocols. Conclusion MTHFR polymorphisms are potential risk factors for adverse pregnancy outcomes.

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Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and high plasma homocysteine in chronic hepatitis C (CHC) infected patients from the Northeast of Brazil

Nutrition Journal ◽

10.1186/1475-2891-10-86 ◽

2011 ◽

Vol 10 (1) ◽

Cited By ~ 3

Author(s):

Erika RF Siqueira ◽

Cláudia PMS Oliveira ◽

Maria TC Muniz ◽

Filipe Silva ◽

Leila MMB Pereira ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

High Plasma ◽

Plasma Homocysteine ◽

C677t Polymorphism ◽

Mthfr C677t Polymorphism

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Correlation between ZBRK1/ZNF350 gene polymorphism and breast cancer

BMC Medical Genomics ◽

10.1186/s12920-020-00862-2 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Jun Wu ◽

Alibiati Eni ◽

Eliar Roussuri ◽

Binlin Ma

Keyword(s):

Breast Cancer ◽

Family History ◽

Gene Polymorphism ◽

Zinc Finger ◽

Zinc Finger Protein ◽

Control Groups ◽

Wild Genotype ◽

Mutant Genotype ◽

Synonymous Mutations ◽

Significant Difference

Abstract Background This study is to explore the relationship between the ZBRK1/ZNF350 (Zinc finger and BRCA1-interacting protein with KRAB domain-1; also known as zinc-finger protein 350) gene polymorphism and early-onset breast cancer. Methods The ZBRK1/ZNF350 gene exon detection analysis was performed with the direct sequencing and Snapshot methods in 80 cases of breast cancer (aged ≤ 40 years old) and 240 healthy subjects (aged ≤ 40 years old). Results Totally 9 sequence variants were detected, including 5 missense mutations and 4 synonymous mutations, located at EXON3, EXON4 and EXON5, respectively. The rs4987241 and rs3764538 variants were published for the first time, while the remaining variants had been reported before. There were significant differences in the frequency distribution of family history between the breast cancer and control groups. Moreover, there were significant differences in the CT genotype frequency at the rs138898320 locus between the breast cancer and healthy control groups. Compared with the carriers of CC wild genotype at rs138898320, the risk of breast cancer was reduced by 88.3% in the CT mutant genotype carriers, with significant difference. In the stratification with no family history, compared with the carriers of CC wild genotype at rs138898320, significant differences were observed for the CT mutant genotype carriers. In the stratification with family history, there was no significant difference in the variation of rs138898320. Conclusion The rs138898320 CT mutation genotype of ZBRK1/ZNF350 may reduce the risk of breast cancer, and the protecting effect would be increased in the stratification with no family history. Trial registration Not applicable.

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Effect of maternal serum B vitamins, homocysteine levels and the 5, 10‐methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on postnatal growth measurements in their infants

The FASEB Journal ◽

10.1096/fasebj.20.4.a602 ◽

2006 ◽

Vol 20 (4) ◽

Author(s):

Hyesook Kim ◽

Young Ju Kim ◽

Ki Nam Kim ◽

Namsoo Chang

Keyword(s):

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Postnatal Growth ◽

Maternal Serum ◽

B Vitamins ◽

C677t Polymorphism ◽

Mthfr C677t Polymorphism

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Effect of riboflavin supplementation on blood pressure and possible effect modification by the MTHFR C677T polymorphism: a randomised trial in rural Gambia

F1000Research ◽

10.12688/f1000research.25113.1 ◽

2020 ◽

Vol 9 ◽

pp. 1034

Author(s):

Modou Jobe ◽

Mary Ward ◽

Bakary Sonko ◽

Abdul Khalie Muhammad ◽

Ebrima Danso ◽

...

Keyword(s):

Blood Pressure ◽

Large Scale ◽

Methylenetetrahydrofolate Reductase ◽

Controlled Trial ◽

Randomised Trial ◽

Mthfr C677t ◽

C677t Polymorphism ◽

Phenotypic Effect ◽

Riboflavin Deficiency ◽

Mthfr C677t Polymorphism

Introduction: Emerging evidence links a functional polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene (rs1801133) with hypertension in adults. This variant reduces the affinity of MTHFR for its cofactor flavin-adenine dinucleotide (FAD) which is derived from riboflavin. Previous work has demonstrated a blood pressure (BP)-lowering effect of riboflavin in Irish adults with the MTHFR 677TT variant. We hypothesize that the almost-universal severe riboflavin deficiency seen in rural Gambia mimics the BP phenotypic effect of the TT variant and exacerbate the effect of the CT variant. We will test this in a randomised, placebo-controlled trial, whether intervention with riboflavin can decrease BP in adults in rural Gambia. Methods: This is a phase 2 recall-by-genotype randomised single-blind placebo-controlled riboflavin supplementation trial. We will use the Keneba biobank to recruit approximately 102 individuals aged between 18-70, previously genotyped for the MTHFR C677T polymorphism and identified as carrying the T allele; these individuals will be age- and sex-matched to a similar number of homozygotes for the C allele. The participants will be randomised to a 16-week supplementation trial of 5 mg/day riboflavin or placebo, supplied every 14 days. The primary outcome, BP, will be measured at baseline and at weeks 8 and 16. Blood samples, collected at baseline and week 16, will be analysed for riboflavin, homocysteine, red cell folate, cobalamin (vitamin B12) and pyridoxine (vitamin B6). Discussion: The study will evaluate the role of riboflavin supplementation in BP control within a population with high levels of riboflavin deficiency and will test a possible gene-nutrient interaction with the MTHFR C677T polymorphism. If improvements in BP are observed in this study, and proven in subsequent large-scale interventions, riboflavin could offer a cost-effective, safe and accessible option for the prevention and control of hypertension in this population. Trial registration: ClinicalTrials.gov Identifier NCT03151096. Registered on 12 May 2017.

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MTHFR Gene Polymorphism and Age of Onset of Schizophrenia and Bipolar Disorder

BioMed Research International ◽

10.1155/2014/318483 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 12

Author(s):

Mohamed A. El-Hadidy ◽

Hanaa M. Abdeen ◽

Sherin M. Abd El-Aziz ◽

Mohammad Al-Harrass

Keyword(s):

Bipolar Disorder ◽

Healthy Subjects ◽

Methylenetetrahydrofolate Reductase ◽

Age Of Onset ◽

Age At Onset ◽

Mthfr C677t ◽

Control Group ◽

C677t Polymorphism ◽

Mthfr C677t Polymorphism ◽

Mthfr Gene Polymorphism

Objective. Several studies with contradictory results from different cultures about association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in schizophrenia and bipolar disorders. Little is known about this association in Arab culture and Egypt. So the present study aimed to assess the association of MTHFR C677T polymorphism in bipolar disorder (BD) and schizophrenia in comparison to control group. The association between MTHFR C677T polymorphism and the age at onset in schizophrenia or BD was also studied.Methods. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to examine the genotype and allele frequencies of MTHFR C677T polymorphism in 149 healthy subjects and 134 bipolar and 103 schizophrenia patients.Results. In BD and schizophrenia, there was a higher prevalence of MTHFR C677T polymorphism than healthy subjects. Earlier age at onset was found in patients with BD, carrying one copy of the T allele or CT genotypes but not in patients with schizophrenia.Conclusion. The present findings suggest that the MTHFR C677T polymorphisms are likely to be associated with the risk of developing BD and schizophrenia and influence the age at onset of BD but not the age at onset of schizophrenia.

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