The length of the CTLA-4 microsatellite (AT)N-repeat affects the risk for type 1 diabetes. Diabetes Incidence in Sweden Study Group

• Published in: Autoimmunity (Chur, Switzerland) Vol. 32; no. 3; p. 173
• Main Authors: Lowe, R M, Graham, J, Sund, G, Kockum, I, Landin-Olsson, M, Schaefer, J B, Törn, C, Lernmark, A, Dahlquist, G
• Format: Journal Article
• Language: English
• Published: England 01.10.2000
• Subjects: Abatacept; Adolescent; Adult; Alleles; Antigens, CD; Antigens, Differentiation - genetics; Child; Child, Preschool; CTLA-4 Antigen; Diabetes Mellitus, Type 1 - genetics; Dinucleotide Repeats; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Immunoconjugates; Infant; Infant, Newborn; Male; Polymorphism, Genetic; Sweden; Sweden
• ISSN: 0891-6934; 1607-842X
• DOI: 10.3109/08916930008994090

CTLA-4 is important to down-regulating T cell responses and has been implicated in type 1 (insulin dependent) diabetes mellitus in both linkage and association studies. The aim of our study was to relate the polymorphic (AT)n microsatellite in the 3' untranslated sequence of the CTLA-4 gene to diabetes risk. We studied 616 consecutively diagnosed 0-34 year-old Swedish patients and 502 matched controls by PCR-based genotyping fo determine the length of the 3'-end (AT)n repeat region of the CTLA-4 gene and categorizing alleles as predominantly monomorphic short (S) or highly polymorphic (in length) 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 genotype (95% CI 1.44-2.73, p=0.002). Further analysis of the long alleles, partitioned into intermediate (I) length and very long (VL) alleles, suggested that L alleles act recessively in conferring diabetes risk (p=0.0009). This study suggests that the 3'-end (AT)n repeat region of the CTLA-4 gene represents a recessive risk factor for type 1 diabetes.