Abstract 3457: Methylenetetrahydrofolate Reductase Gene Polymorphism C677T And The Risk Of Premature Myocardial Infarction With “Normal” Coronary Arteries.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Loukianos Rallidis ◽  
Christoforos Komborozos ◽  
Argyri Gialeraki ◽  
Maria Zolindaki ◽  
Panagiotis Vavoulis ◽  
...  

Purpose: the pathogenetic mechanism of acute myocardial infarction (AMI) in young patients remains unknown. We explored the impact of homocysteine and its main genetic modulator Table 2 methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in patients who sustained AMI under the age of 36 years. Methods: we recruited 136 consecutive patients who had survived their first AMI before the age of 36 years (mean age=32 ± 3.1 years, range 23–35 years, 121 men). Blood was taken for lipids and homocysteine levels within 12 hours from admission. The MTHFR C677T polymorphism was also determined with polymerase chain reaction. All patients underwent cardiac catheterization. One hundred-three healthy individuals without a family history of coronary heart disease (CHD), matched for age and sex served as controls. Results: coronary angiogram revealed significant CHD in 104 patients while 32 (23.5%) had no significant CHD. The prevalence of homozygotes for C677T polymorphism [T/T genotype] was 27.2% in patients and 14.6% in controls (p=0.02). In the subgroup of patients who had AMI and “normal” coronary arteries the frequency of homozygotes was 43.8% (p=0.001 versus controls and p=0.02 versus patients with significant CHD). The table presents lipids and homocysteine levels in AMI patients with “normal” coronary arteries and controls. Logistic regression model showed that the odds ratio for a young individual with T/T genotype to develop AMI with “normal” coronary arteries was 5.2 (confidence interval 1.2–23, p=0.03) adjusted for smoking habits, body mass index, hypertension and diabetes mellitus. Conclusions: the presence of homozygocity for MTHFR C677T polymorphism is associated with 5-fold higher risk for premature AMI with “normal” coronary arteries. This suggests that homocysteine may be involved in the formation of an obstructive thrombus in coronary arteries, especially in young individuals without significant underlying atheromatic burden.

2009 ◽  
Vol 28 (1) ◽  
pp. 41-45 ◽  
Author(s):  
Anđelo Beletić ◽  
Duško Mirković ◽  
Nebojša Antonijević ◽  
Valentina Đorđević ◽  
Violeta Šango ◽  
...  

Incidence of Hyperhomocysteinemia and Mthfr C677T Polymorphism Among Young Patients with Acute Myocardial Infarction Hyperhomocysteinemia is considered an independent risk factor for premature cardiovascular disease. Mutation MTHFR C677T reduces the activity of methylenetetra-hydrofolatereductase and may cause hyperhomocysteinemia. Incidence of hyperhomocysteinemia (homocysteine above 12 μmol/L), homocysteine level, and distribution of MTHFR C677T genotypes (C/C, C/T and T/T) are compared between young patients with acute myocardial infarction and healthy persons, matched by age. Study involved 86 patients younger than 45 years (77 men and 9 women) and 35 controls. Homocysteine was measured by an HPLC method and the MTHFR C677T genotype determined using PCR amplification and digestion with Hinf I. Statistical analyses included chisquare and Mann-Whitney U tests. Hyperhomocysteinemia was present in 32.6% patients and 14.3% controls, revealing a significant difference (P= 0.038). Median homocysteine levels in patients (10.4 μmol/L) and controls (9.6 μmol/L) were significantly different (P=0.035). Among patients, 50.0% had C/C, 41.9% C/T and 8.1% T/T genotype, and the genotype had no influence on hyperhomocysteinemia incidence and homocysteine level. Genotype distribution in patients was not significantly different from that observed in controls. The conclusion is that young patients with acute myocardial infarction have higher incidence of hyperhomocysteinemia and higher homocysteine levels than healthy young adults, while there is no significant difference in the distribution of MTHFR C677T genotypes.


F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1034
Author(s):  
Modou Jobe ◽  
Mary Ward ◽  
Bakary Sonko ◽  
Abdul Khalie Muhammad ◽  
Ebrima Danso ◽  
...  

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.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Mohamed A. El-Hadidy ◽  
Hanaa M. Abdeen ◽  
Sherin M. Abd El-Aziz ◽  
Mohammad Al-Harrass

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.


2019 ◽  
Author(s):  
Widya Dwi Honesty Putri Soewarlan ◽  
Hedijanti Joenoes ◽  
Shafa Ahmad Bawazier ◽  
Dwi Anita Suryandari ◽  
Elza Ibrahim Auerkari

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