Gene polymorphisms in the TNF locus and the risk of myocardial infarction

We investigated two genetic polymorphisms in the tumor necrosis factor locu s (TNF-alpha -308 G-->A and LT-alpha +252 A-->G) as risk factors for corona ry atherothrombotic disease (CAD) by determining its prevalence in 148 surv ivors of myocardial infarction (MI) with angiographically-proven severe CAD , and in 148 age-, gender- and race-matched controls. The odds ratio (OR) f or MI related to the mutant TNF-alpha and LT-alpha alleles was 0.8 (CI95: 0 .4-1.3) and 1.3 (CI95: 0.8-2.0), respectively. We also sought interaction o f smoking and metabolic risk factors for MI with each mutant genotype. Smok ers not carrying the LT-alpha +252 A-->G mutation had a risk of MI of 2.7 ( CI95: 1.4-5.4) whereas in smoking carriers the risk was 6.9 (CI95: 3.4-14.1 ). An interactive effect of the LT-a mutation may also exist with dyslipide mia (OR for MI in non-carriers was 12 [CI95: 3.2-41.3] and in carriers the OR was 39, [CI95: 5.1-301] and with obesity (OR for MI was 2.7, [CI95: 1-7. 2] in non-carriers and in carriers the OR was 6 [CI95: 2.1-16.8]). Lastly, the OR for MI in obese non-carriers of TNF-alpha -308 G-->A was 2.8 (CI95: 1.3-6) and in obese carriers the OR was 14.5 (CI95: 1.8-113). Although sign ificant interactive effects could not be detected, the findings suggest tha t interaction of polymorphisms in the TNF locus with major risk factors for CAD may exist, and should be explored in larger studies. (C) 2000 Elsevier Science Ltd. All rights reserved.