Family history, plasma homocysteine, and age at onset of symptoms of myocardial ischemia in patients with different methylenetetrahydrofolate reductase genotypes.
ABSTRACT A high plasma homocysteine level is associated with early onset of coronary artery disease (CAD), particularly in homozygotes for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Family history is a predictor of increased plasma homocysteine and may be involved in early-onset CAD. This study examined the relations among family history, plasma homocysteine, and age at onset of CAD, and the role of the MTHFR genotype in this context. We screened 284 patients who developed first symptoms of CAD at < or =65 years of age for fasting plasma homocysteine and the C677T mutation. On multiple regression analysis, homocysteine, family history, male gender, and smoking were independently associated with age at onset of CAD. However, separate analysis of patients who had the MTHFR 677 T/T genotype (n = 57) and those who did not (n = 209) showed that plasma homocysteine and family history were associated with earlier onset of CAD only in T/T homozygotes and that family history in patients who had this genotype was also associated with higher plasma homocysteine levels and a stronger association between plasma homocysteine and age at onset of CAD. In patients who had other genotypes, these associations were not observed, and earlier onset of CAD was associated only with male gender and smoking. Thus, the MTHFR genotype modifies the effects of family history and other risk factors on age at onset of CAD. In T/T homozygotes, family history is associated with earlier onset of CAD, higher plasma homocysteine levels, and a stronger association between plasma homocysteine and age at onset of CAD.
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ABSTRACT: Elevated homocysteine is associated with increased risk for coronary artery disease (CAD) in adults, but its distribution in children is not well documented. We examined the distribution of homocysteine in children and its relation to parental history of CAD. A subsample of 1137 children (53% white, 47% black) aged 5 to 17 years in 1992 to 1994 examined in the Bogalusa Heart Study (n=3135), including all with a positive parental history of CAD (n=154), had plasma homocysteine levels measured. Homocysteine correlated positively with age (r=0.16, P=0.001). No race or sex differences in homocysteine levels were observed; geometric mean (GM) levels were 5.8 micromol/L (95% CI, 5.6 to 6.1) among white males, 5.8 micromol/L (95% CI, 5.5 to 6.0) among white females, 5.6 micromol/L (95% CI, 5.4 to 5.8) among black males, and 5.6 micromol/L (95% CI, 5.4 to 5.9) among black females. Children with a positive parental history of CAD had a significantly greater age-adjusted GM homocysteine level (GM, 6.7 micromol/L; 95% CI, 6.4 to 7.1) than those without a positive history (GM, 5.6 micromol/L; 95% CI, 5.4 to 5.7); this relation was observed in each race-sex group. Higher homocysteine levels were observed among children with a positive family history of CAD. Additional studies should elucidate the contribution of genetic, dietary, and other factors to homocysteine levels in children.Circulation 05/1999; 99(16):2144-9. · 15.20 Impact Factor
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ABSTRACT: Extensive clinical and statistical studies have identified risk factors that increase the incidence of coronary heart disease. It is commonly suggested that more than 50% of patients with coronary heart disease lack any of the conventional risk factors. OBJECTIVE. To determine the prevalence of four conventional risk factors among patients with coronary heart disease. MATERIAL AND METHODS. We analyzed data of 606 patients with coronary heart disease (myocardial infarction, unstable and stable angina pectoris) hospitalized in the Clinics of Santariskes, Vilnius University Hospital, in 1997-2005. RESULTS. Among patients with coronary heart disease, at least one of four conventional risk factors was present in 98% of patients. Hypertension was present in 47.7% of patients, diabetes - in 12.9%, dyslipidemia - 90.1%, and smoking - in 24.1% of patients. In younger patients (<55 years), only 2.3% of patients lacked any of four conventional risk factors. Two-thirds (66.5%) of younger patients with coronary heart disease had two and more risk factors. CONCLUSIONS. Considering the fact that patients with coronary heart disease often lack conventional risk factors, currently more attention is given to nontraditional risk factors as well as genetic causes of coronary heart disease. Nevertheless, the present study revealed that 98% of patients with coronary heart disease had at least one of four conventional risk factors. Among younger patients (younger than 55 years), conventional risk factors are identified very frequently. Thus, it can be concluded that in order to reduce the epidemic of coronary heart disease, much greater emphasis should be given to identify and to improve prevention of four conventional risk factors as well as the lifestyle of the patient.Medicina (Kaunas, Lithuania) 02/2009; 45(2):140-6. · 0.55 Impact Factor
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ABSTRACT: Homozygosity for the common (677C-->T) mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with hyperhomocysteinemia, but there is uncertainty as to the association between this mutation and coronary artery disease (CAD). This study examined the association between MTHFR genotypes and age at onset of CAD. Patients (n=169) with documented myocardial infarction or angiographically documented CAD who were aged < or = 55 years at onset of CAD symptoms and DNA samples from control subjects (n=313) were studied. The prevalence of homozygosity among patients with early CAD onset (aged < or = 45 years) was 28%, which was significantly higher than that in patients with later onset (13%) and in control subjects (14%) (odds ratio 2.4, 95% CI 1.24 to 4.69, P=0.006, and odds ratio 2.7, 95% CI 1.15 to 6.42, P=0.01, respectively). Plasma folate was lower in TT homozygotes who had early CAD onset than in those with later onset (P=0.005). Among patients with plasma folate in the lowest quintile (< or = 12.6 nmol/L), 31% were homozygotes, as were 45% of those with low plasma folate and early CAD onset. There was no difference in the prevalence of traditional risk factors among genotypes. The frequency of homozygosity in patients with < or = 1 risk factor was higher than in those with > or = 2 risk factors (30% versus 12%, P<0.05). In multiple regression analysis, TT homozygosity and plasma folate were independently associated with CAD, but the impact of folate was small. Homozygosity for the 677C-->T mutation of MTHFR is common and is associated with an increased risk of premature CAD in this population.Circulation 12/1999; 100(24):2406-10. · 15.20 Impact Factor