Polymorphism in the MHC2TA gene is associated with features of the metabolic syndrome and cardiovascular mortality

Abstract

Background: Recently, a -168A-->G polymorphism in the MHC class II transactivator gene (MHC2TA) was shown to be associated with increased susceptibility to myocardial infarction (MI).

Aim: To confirm the association between the MHC2TA -168A-->G polymorphism and MI and to study its putative role for microalbuminuria, the metabolic syndrome (MetS) and cardiovascular mortality.

Materials and methods: Using an allelic discrimination method we genotyped 11,064 individuals from three study populations: 1) 4,432 individuals from the Botnia type 2 diabetes (T2D) study, 2) 1,222 patients with MI and 2,345 control subjects participating in the Malmö Diet and Cancer study and comprising an MI case-control sample, and 3) 3,065 T2D patients from the Local Swedish Diabetes registry.

Results: No association between the -168A-->G polymorphism in MHC2TA and MI was observed. However, in the Botnia cohort the AG/GG genotypes were associated with cardiovascular mortality after MI (1.78 [1.09-2.92], p = 0.02). In addition, the AG/GG genotypes were more common in subjects with MetS (40.1% vs. 36.9%, p = 0.03) and in non-diabetic subjects with microalbuminuria (45.4% vs. 36.5%, p = 0.003) compared to control subjects.

Conclusions: A polymorphism in MHC2TA was associated with cardiovascular mortality and predictors of cardiovascular mortality, microalbuminuria and MetS.

Figure 1

Cardiovascular mortality in the Botnia cohort in patients with previous MI according to MHC2TA -168 A→G genotypes. Kaplan Meier survival curves illustrating a higher risk for CV mortality (HR 1.76 [1.09–2.82], p = 0.02) in AG/GG genotype carriers with previous history of MI.