The Length of the CTLA-4 Microsatellite (AT)N-Repeat Affects the Risk for Type 1 Diabetes: For the Swedish Childhood Diabetes Study Group
- 1 January 2000
- journal article
- research article
- Published by Taylor & Francis in Autoimmunity
- Vol. 32 (3) , 173-180
- https://doi.org/10.3109/08916930008994090
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 to 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 diabetesKeywords
This publication has 23 references indexed in Scilit:
- Genetic association of Ctla-4 to myasthenia gravis with thymomaJournal of Neuroimmunology, 1998
- CTLA4 Gene Polymorphism Confers Susceptibility to Graves' Disease in JapaneseThyroid®, 1997
- Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groupsHuman Molecular Genetics, 1997
- An Mse I RFLP in the Human CTLA4 PromotorBiochemical and Biophysical Research Communications, 1996
- The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes RegistryHuman Molecular Genetics, 1996
- Genetic markers in diagnosis and prediction of relapse in Graves’ disease*Experimental and Clinical Endocrinology & Diabetes, 1996
- Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4Immunity, 1995
- A genome-wide search for human type 1 diabetes susceptibility genesNature, 1994
- Epidemiology of Diabetes Mellitus in SwedenActa Medica Scandinavica, 1986
- The epidemiology of diabetes in Swedish children 0?14 years ? a six-year prospective studyDiabetologia, 1985