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).


CONCLUSIONS
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.
Pegoraro
R J
RJ
Department of Chemical Pathology, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban.
Ranjith
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Rom
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D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000235:genetics*; D016022:Case-Control Studies; D005167:Factor VII / Q000235:genetics / Q000378:metabolism; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India / Q000208:ethnology; D008075:Lipoproteins, HDL / Q000097:blood / Q000235:genetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009203:Myocardial Infarction / Q000208:ethnology* / Q000235:genetics*; D009765:Obesity / Q000208:ethnology / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000208:ethnology / Q000235:genetics; D013019:South Africa / Q000453:epidemiology / Q000208:ethnology; D016277:Ventricular Function, Left / Q000235:genetics
D015415:Biomarkers; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D005167:Factor VII; D005340:Fibrinogen