C282Y mutation in the HLA-H gene is not a risk factor for patients with myocardial infarction.

BACKGROUND: Iron is suspected to play a role in the development of atherosclerosis and in the progression of the disease, and consequently in myocardial infarction. Authors of a recent study identified a mutation in HLA-H gene, C282Y, that is an excellent marker for hemochromatosis, which is the most common cause of iron overload. There is a high prevalence of carriers of heterozygous hemochromatosis, most of whom are asymptomatic even with abnormalities of iron metabolism. OBJECTIVE: To study C282Y mutation in the HLA-H gene of 173 survivors of myocardial infarction matched with 172 controls by age, race, and sex, and 119 patients upon diagnosis of acute myocardial infarction. METHODS: Identification of the mutation was performed by PCR amplification of the DNA fragment followed by Rsal digestion. RESULTS: The prevalence of heterozygotes for the mutated allele both among patients and among controls was 1.74%. None of the 119 patients studied upon diagnosis was a carrier of the mutation. CONCLUSION: Our data suggested that the most common cause of iron overload is not associated with myocardial infarction.

Prevalence of the prothrombin gene variant 20210 G --> A among patients with myocardial infarction.

OBJECTIVE: The aim of this study was to determine the prevalence of the prothrombin variant allele 20210A among survivors of myocardial infarction. BACKGROUND: The prothrombin gene variant has been identified as a novel genetic risk factor for venous thrombosis. However, the risk of developing arterial thrombosis as a result of the presence of this mutated allele is unknown. METHODS: The G-->A transition at position 20210 of the 3'-untranslated region was determined in 220 survivors of myocardial infarction and in 295 individuals from the general population. RESULTS: The prevalence of heterozygotes for the prothrombin mutated allele was 3% among patients with myocardial infarction and 0.7% in the general population (P = 0.03). No age-related difference in the prevalence of the mutated allele was observed. However, for individuals over 45 years old the prevalence among females was higher than among males (5% vs. 0%). CONCLUSION: These data suggest that being heterozygote for the allele variant 20210A of the prothrombin gene could be a genetic risk factor for developing myocardial infarction.

The mutation Ala677-->Val in the methylene tetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis.

Mild hyperhomocysteinemia has been identified as a risk factor for arterial disease and for venous thrombosis. Individuals homozygous for the thermolabile variant of the methylene tetrahydrofolate reductase gene (MTHFR) which results from a common mutation Ala677-->Val and is found in 5-15% of the general population, have significantly elevated plasma homocysteine levels and may account for one of the genetic risk factors in vascular disease. We have analyzed the prevalence of MTHFR-T homozygotes in patients with arterial disease or venous thrombosis. We studied 191 patients with arterial disease and 127 individuals with venous thrombosis and compared with 296 unmatched controls. The results showed that there was a high prevalence of homozygotes for the mutated MTHFR-T allele among a group of patients with arterial disease (19%) in the absence of hyperlipoproteinemia, hypertension, and diabetes mellitus when compared to controls (4%), odds ratio of 5.52 (95% C.I., 2.27 to 13.51). The prevalence of homozygotes among patients with venous thrombosis was 11%, odds ratio of 2l93 (95% C.I., 1.23 to 7.01). The risk of venous thrombosis remained high, odds ratio of 2.63, even after we excluded 27 patients with hereditary thrombophilia (e.g. factor V Leiden, dysfibrinogenemia, deficiency of protein C, protein S, antithrombin III, or factor XII) from the 127 overall cases with venous thrombosis. These data support the hypothesis that being a homozygote for the MTHFR-T is a risk factor for the development of arterial disease and also for venous thrombosis.