Type II diabetes mellitus and polymorphism of insulin-receptor gene in Mexican Americans

Resistance to insulin action is a well-established feature of type II (non-insulin-dependent) diabetes and is believed by many to contribute to the etiology of this condition. We therefore characterized restriction-fragment-length polymorphisms of the insulin-receptor gene with the restriction enzyme Rsa I in 242 Mexican Americans and non-Hispanic Whites with type II diabetes and 202 age-, sex-, and ethnicity-matched control subjects who participated in a population-based study in San Antonio. Alleles of 6.7 kilobasis (kb) (A allele), 6.2 kb (B allele), and 3.4 kb (C allele) were identified. The C allele was observed in Mexican Americans only, where its frequency among nondiabetic control subjects was 17.7%. Diabetic Mexican Americans were twice as likely as control subjects to be homozygous for the C allele. The crude odds ratio for diabetes in CC homozygotes compared with the other two genotypes was 2.22, although this result was not statistically significant (χ² = 1.57, P = .21). The Mantel-Haenszel odds ratio, adjusting for age, however, indicated a 4.71-fold increased risk of diabetes among Mexican Americans with the CC genotype compared with Mexicans Americans without this genotype (χ²(M-H) = 5.38, P = .020). The age of onset of diabetes was also slightly younger in CC homozygote cases (45.4 ± 9.2 yr) than in CX or XX cases (47.7 ± 9.0 and 48.6 ± 9.6 yr, respectively), although this difference was not statistically significant (P .467). The C allele may be involved directly in the etiology of type II diabetes, or it may be in linkage disequilibrium with a functionally significant region of the insulin receptor gene.