Original ArticleClinicalC677T Polymorphism of the 5,10 MTHFR Gene in Young Mexican Subjects with ST-Elevation Myocardial Infarction
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)
- et al.
INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study
Lancet
(2004) - et al.
Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms, plasma homocysteine, folate, and vitamin B12 levels and the extent of coronary artery disease
Am J Cardiol
(2004) - et al.
The 677 C/T MTHFR polymorphism is associated with essential hypertension, coronary artery disease, and higher homocysteine levels
Arch Med Res
(2008) - et al.
An association of 5,10- methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and ischemic stroke
J Stroke Cerebrovasc Dis
(2005) - et al.
Role of methylenetetrahydrofolate reductase 677C->T polymorphism in the development of premature myocardial infarction
Atherosclerosis
(2008) - et al.
Prevalence of myocardial infarction is related to hyperhomocysteinemia but not influenced by C677T methylenetetrahydrofolate reductase and A2756G methionine synthase polymorphisms in diabetic and non-diabetic subjects
Clin Chim Acta
(2005) - et al.
High prevalence of the thermolabile methylenetetrahydrofolate reductase variant in Mexico: a country with a very high prevalence of neural tube defects
Mol Genet Metab
(1999) - et al.
Methylenetetrahydrofolate reductase C677T polymorphism and factor V Leiden variant in Mexican women with preeclampsia/eclampsia
Blood Cells Mol Dis
(2005) - et al.
The C677T polymorphism of the methylenetetrahydrofolate reductase gene in Mexican mestizo neural-tube defect parents, control mestizo and native populations
Ann Genet
(2000) - et al.
The 677C–>T mutation in the methylenetetrahydrofolate reductase gene: associations with plasma total homocysteine levels and risk of coronary atherosclerotic disease
Atherosclerosis
(1997)