Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups

Linkage disequilibrium (association) analysis was used to evaluate acandidate region near the CTLA4/CD28 genes using a multi-ethnic collectionof families with one or more children affected by IDDM. In the data setunique to this study (Spanish, French, Mexican-American, Chinese andKorean), the transmission/disequilibrium test (TDT) revealed a highlysignificant deviation for transmission of alleles at the (AT)nmicrosatellite marker in the 3' untranslated region (P = 0.002) and the A/Gpolymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overallevidence for transmission deviation of the CTLA4 A/G alleles is also highlysignificant (P = 0.00005) in the combined data set (669 multiplex and 357simplex families) from this study and a previous report on families fromUSA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observedin these data sets. The British, Sardinian and Chinese data sets did notshow any deviation for the A/G polymorphism, while the Caucasian-Americandata set showed a weak transmission deviation. Strong deviation fortransmission was seen in the three Mediterranean-European populations(Italian, Spanish and French) (P = 10(-5)), the Mexican-American population(P = 0.002) and the Korean population (P = 0.03). These results suggestthat a true IDDM susceptibility locus (designated IDDM12) is located nearCTLA4.