Original Article
Clinical
C677T Polymorphism of the 5,10 MTHFR Gene in Young Mexican Subjects with ST-Elevation Myocardial Infarction

https://doi.org/10.1016/j.arcmed.2010.04.008Get rights and content

Background and Aims

The C677T polymorphism of 5,10 methylenetetrahydrofolate reductase (MTHFR) gene has been associated with hypertension and coronary artery disease in several populations worldwide, but results are still controversial. The aim of this study was to examine the possible association of C677T polymorphism with ST-elevation myocardial infarction (STEMI) in young Mexican subjects.

Methods

In a case-control study, 167 unrelated patients ≤45 years of age with diagnosis of STEMI who were admitted to a cardiovascular intense care unit and 167 unrelated controls subjects matched by age and gender were recruited from January 2006 and June 2009. The C677T polymorphism was determined in all participants by a polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP).

Results

There was no significant difference in the genotype distribution between groups (p = 0.69) or allele frequency (p = 0.40). There were independent factors for STEMI: smoking (OR 4.9, 95% CI 3.0–8.1, p = 0.001), hypertension (OR 1.8, 95% CI 1.0–3.3, p = 0.03), family history of atherothrombotic disease (OR 2.3, 95% CI 2.0–4.6, p = 0.02), and dyslipidemia (OR 3.2, 95% CI 1.8–5.6, p <0.001). Diabetes mellitus did not represent an independent risk factor for STEMI (OR 1.2, 95% CI 0.2–2.2, p = 0.82).

Conclusions

The TT genotype from the C677T of 5,10 MTHFR gene is not an independent risk factor for STEMI in the Mexican population. However, more studies are needed to determine the possible “protective effect” of the C677T polymorphism in our population.

Introduction

The major thrombosis complication of CAD is ST-elevation myocardial infarction (STEMI) (1), representing a very important care health issue in our country (2). It is estimated that ∼10% occurred in young individuals (2). The pathogenic mechanism of myocardial infarction (MI) is complex and involves the interaction of multiple environmental and genetics factors. Environmental risk factors such as diabetes mellitus, hypertension, hyperlipidemia, obesity and smoking account for ∼50% of the risk for development of myocardial infarction (MI). The remaining risk is attributed to genetic factors. Previous studies demonstrated a higher proportion of heavy smoking, dyslipidemia, family history of atherothrombotic disease, with a low prevalence of diabetes and hypertension as risk factors for MI in young individuals. In addition, high levels of homocysteine (Hcy) have been associated with increased risk for MI (3). Plasma Hcy levels are modulated by nutritional and genetic factors, among which the methylenetetrahydrofolate reductase (MTHFR) gene has received special attention, in particular, the C677→T in the gene coding the MTHFR, which is characterized by a point mutation at position 677 of the MTHFR gene resulting in Val→Ala substitution responsible for enzyme reduced activity (4). Subjects who were homozygous for 677T polymorphism had a mildly increased risk for hyperhomocysteinemia, especially if subjects have low plasma folate levels (5). Previous studies found an association between the MTHFR 6777CT polymorphism and the risk of myocardial infarction 6, 7, 8, 9, hypertension (9), and cerebrovascular disease 10, 11. However, these findings have not been confirmed by others 12, 13, 14, 15, 16, 17. A meta-analysis (18) of a case-control observation of 40 studies reported a higher risk of MI of individuals with the MTHFR 677TT genotype, although a significant heterogeneity between Europe and North America was observed. In contrast, another later meta-analysis (19) did not support this association in Europe, North America or Australia. Although a high frequency of the T allele has been demonstrated in the general Mexican population compared with individuals from other genetic backgrounds (20), this polymorphism exhibited a negative correlation with some disease such as preeclampsia/eclampsia (21), gastric cancer (22), and neural tube defects (23). In contrast, we previously demonstrated that C677T represents an independent risk for other atherothrombotic diseases such as stroke in Mexican subjects (24).Therefore, the aim of this study was to examine the possible association of C677T polymorphism in young Mexican subjects with STEMI.

Section snippets

Study Group

This case-control study included 167 consecutive patients who survived their first STEMI. Diagnosis of STEMI was based on an electrocardiogram and clinical and laboratory data in accordance with the European Society of Cardiology and American College of Cardiology 25, 26. Patients were admitted to the Intensive Coronary Care Unit of the Cardiology Hospital, Centro Médico Nacional Siglo XXI in Mexico City between January 2006 and June 2009. Clinical and demographic data were recorded. Other risk

Results

Baseline characteristics of patients and controls are shown in Table 1. The study population was comprised of 167 patients all ≤45 years of age with a diagnosis of STEMI, and 167 age- and gender-matched controls. Body mass index was similar between groups (p = 0.50). The prevalence of risk factors was high among the group of patients, and those associated with STEMI were diabetes mellitus (29.34 vs. 13.17%, OR 2.74; 95% CI 1.51–4.98, p <0.001), hypertension (34.13 vs. 14.97%, OR 2.94; 95% CI

Discussion

MI is the first cause of mortality worldwide and the prevalence among young people has increased during the last decade, representing almost 10% of the total MIs. Several factors and probably several genes are involved in the pathogenesis of MI. Previous reports from different populations identified an association of homozygous MTHFR 677T genotypes with increased plasma Hcy concentration, especially in the presence of low folate and/or increased risk for MI 3, 6, 7, 8, whereas other studies

Conflict of Interest

None declared.

Acknowledgments

This research was supported by Fondo de Investigación en Salud (IMSS) grant (FIS/IMSS/PROT/171 and FIS/IMSS/PROT/043) of Mexico (to II-S). AL-M is a recipient of the Research Career Development Award from Fundación IMSS, México.

References (37)

  • I. Isordia-Salas et al.

    Association of the plasminogen activator inhibitor-1 gene 4G/5G polymorphism with ST elevation acute myocardial infarction in young patients

    Rev Esp Cardiol

    (2009)
  • Instituto Nacional de Estadística, Geografía e Informática

    Censo Nacional de Población y Vivienda

    (2007)
  • P. Frosst et al.

    A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase

    Nutr Genet

    (1995)
  • L. Brattström et al.

    Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis

    Circulation

    (1998)
  • L. Ghazouani et al.

    Homocysteine and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Tunisian patients with severe coronary artery disease

    J Thromb Thrombolysis

    (2009)
  • A. Gardemann et al.

    The TT genotype of the methylenetetrahydrofolate reductase C677T gene polymorphism is associated with the extent of coronary atherosclerosis in patients at high risk for coronary artery disease

    Eur Heart J

    (1999)
  • S. Gulec et al.

    Methylentetrahydrofolate reductase gene polymorphism and risk of premature myocardial infarction

    Clin Cardiol

    (2001)
  • K.T. Moe et al.

    Association of acute ischemic stroke with the MTHFR C677T polymorphism but not with NOS3 gene polymorphism in a Singapur population

    Eur J Neurol

    (2008)
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