The length of the CTLA-4 microsatellite (AT)(N)-repeat affects the risk for type 1 diabetes

CTLA-4 is important to down-regulating T cell responses and has been implic ated in type 1 (insulin dependent) diabetes mellitus in both linkage and as sociation studies. The aim of our study was to relate the polymorphic (AT), microsatellite in the 3' untranslated sequence of the CTLA-4 gene to diabe tes risk. We studied 616 consecutively diagnosed 0-34 year-old Swedish pati ents and 502 matched controls by PCR-based genotyping to determine the leng th of the 3'-end (AT)(n)repeat region of the CTLA-4 gene and categorizing a lleles as predominantly monomorphic short (S) or highly polymorphic (in len gth) long (L) alleles. The odds of type 1 diabetes of subjects with the L/L genotype was estimated to be 1.84 times that of subjects with the S/S geno type (95% CT 1.44-2.73, p=0.002). Further analysis of the long alleles, par titioned into intermediate (I) length and very long (VL) alleles, suggested that L alleles act recessively in conferring diabetes risk (p=0.0009). Thi s study suggests that the 3'-end (AT), repeat region of the CTLA-4 gene rep resents a recessive risk factor for type 1 diabetes.