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

Author:
  • Michael R. Lowe
  • J Graham
  • G. Sund
  • I Kockum
  • M. Landin-Olsson
  • Jonathan B Schaefer
  • C. Torn
  • A. Lernmark
  • G Dahlquist
  • G Blohme
Publishing year: 2000
Language: English
Pages: 173-180
Publication/Series: Autoimmunity
Volume: 32
Issue: 3
Document type: Journal article
Publisher: Taylor & Francis

Abstract english

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 diabetes.

Keywords

  • Endocrinology and Diabetes
  • Autoimmunity
  • Diabetes genes
  • Diabetes mellitus
  • IDDM
  • Insulin-dependent diabetes
  • T cells

Other

Published
  • ISSN: 0891-6934
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

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