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Journal:
Nucul Recept. 2005 Nov 25;3:4
Author(s):
Donay AS, Fischer B, Lee SP, Morris AD, Leese G, Palmer CN
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BACKGROUND:
Common variants of the PPARA gene have been found to associate with ischametic heart disease in non diabetic men. The L162V has also been associated with altered lipid measures. We therefore sought to determine the effect of PPARA gene variation on suscptibility to myocardial infarction in patients with type 2 diabetes. 1810 subjects with type 2 diabetes from the prospective Go-DARTS study were genotyped for the L162V and C2528G variants an the PPARA gene and the association of the variants with incident non-fatal mycoardial infarction was examined. Cox's porportional hazards was used to interrogate the tim eto event from recruitment, and linear regression for analysinh association of genotype with quantative clinical traits.
RESULTS:
The V162 allale was associated with decreased risk of non-fatal myocardial infarction (HR = 0.31, 95%CI 0.10-0.93 p = 0.037) wheras the C2528 allele was associated with increased risk (HR = 2.77 95%CI 1.34-5.75 p = 0.006). Similarly V162 was associated with a later mean age of diagnosis with type 2 diabetes C2528 an earlier age of diagnosis. C2528 was also associated with inreased total cholestorol, which did not account for the observed increased risk. Haplotype analysis demonstrated that when both rare variants occurred on the same haplotype the effect of each was abrogated.
CONCLUSIONS:
Genetic variation at the PPARA locus is important in determining cardiovascular risk in both male and female patients with diabetes. This genotype risk appears to be independant of the effect of these genotypes on lipid profiles and age of diagnosis with diabetes.