Association between NIDDM, RH blood group, and haptoglobin phenotype. Results from the San Antonio Heart Study

We examined seven red cell antigen and 10 polymorphic protein phenotypes in 1237 Mexican Americans randomly selected from three San Antonio neighborhoods. Statistically significant associations were found between non-insulin-dependent diabetes mellitus (NIDDM) and RH blood type (X2 = 32.87, df = 10, P = 0.0003) and haptoglobin phenotype (X2 = 9.15, df = 2, P = 0.010). The haptoglobin association showed a dose effect with a single dose of the haptoglobin-1 allele associated with an approximately 50% increase and a double dose of the haptoglobin-1 allele associated with an approximately 100% increase in NIDDM prevalence. Multivariate analysis indicated statistically significant associations between NIDDM and age, sex, adiposity, and neighborhood of residence. However, even after taking these potential confounding variables into account, there was still a significant, independent association between NIDDM and haptoglobin phenotype. The results suggest that the haptoglobin gene may be in linkage disequilibrium with a major susceptibility gene for NIDDM.