title: The length of the CTLA-4 microsatellite (AT)N-repeat affects the risk for type 1 diabetes. Diabetes Incidence in Sweden Study Group.
abstract: 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.
authors.affiliation: Molecular and Cellular Biology Interdepartmental Program, University of Washington, Seattle 98195, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Lowe
authors.forename: J
authors.initials: J
authors.lastname: Graham
authors.forename: G
authors.initials: G
authors.lastname: Sund
authors.forename: I
authors.initials: I
authors.lastname: Kockum
authors.forename: M
authors.initials: M
authors.lastname: Landin-Olsson
authors.forename: J B
authors.initials: JB
authors.lastname: Schaefer
authors.forename: C
authors.initials: C
authors.lastname: Törn
authors.forename: A
authors.initials: A
authors.lastname: Lernmark
authors.forename: G
authors.initials: G
authors.lastname: Dahlquist
mesh_terms: D000069594:Abatacept; D000293:Adolescent; D000328:Adult; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D018900:Dinucleotide Repeats; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018796:Immunoconjugates; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011110:Polymorphism, Genetic; D013548:Sweden
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept