Coagulation gene polymorphisms as risk factors for myocardial infarction in young Indian Asians.

Background: The relationship between pro-coagulant gene polymorphisms, clinical features and the risk of premature coronary heart disease (CHD) in Indian Asian subjects resident in South Africa has been investigated.

Methods: The prevalence of the beta-fibrinogen -455G/A and -148C/T, and the factor VII 10 bp 5' promoter insertion/deletion and R353Q polymorphisms were examined in 195 unrelated Indian Asian patients (< or = 45 years) who presented with myocardial infarction (MI). Results were compared with those from 107 unaffected siblings (18-45 years) and 300 healthy age- and race-matched control subjects.

Results: Overall, none of the polymorphisms examined here showed any association with MI. However, when stratified according to obesity, patients with a BMI > 30 kg/m2 had a significantly higher frequency of the beta-fibrinogen variant alleles, compared with non-obese patients (19% vs 9%; p = 0.025) and controls (19% vs 9%; p = 0.003). Furthermore, the highest frequency of variant alleles occurred in obese smokers (24%), compared with 4% in non-obese non-smokers (p = 0.003) and 9% in control subjects (p < 0.001). The factor VII R353Q and promoter insertion variants, on the other hand, were associated with higher HDL and lower LDL levels (p = 0.034 and 0.04, respectively).

Conclusion: In young Indian Asians who are both obese and smoke, the beta-fibrinogen genetic polymorphisms -455G-->A and -148C-->T, which are in linkage disequilibrium, are significant risk factors for the development of MI. Factor VII genetic variants, namely the 10 bp promoter insertion/deletion and R353Q polymorphisms, may possibly play a protective role through their association with elevated HDL and low LDL levels, respectively.