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Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes

Author:
  • A Gyllenberg
  • Samina Asad
  • F Piehl
  • Maria Swanberg
  • L Padyukov
  • B Van Yserloo
  • E A Rutledge
  • B McNeney
  • J Graham
  • Marju Orho-Melander
  • E. Lindholm
  • C. Graff
  • C Forsell
  • K Åkesson
  • Mona Landin-Olsson
  • G. Forsander
  • S.A. Ivarsson
  • H. Larsson
  • B. Lindblad
  • J Ludvigsson
  • C Marcus
  • Åke Lernmark
  • L Alfredsson
  • Kristina Åkesson
  • I Kockum
  • Annelie Carlsson
Publishing year: 2012
Language: English
Pages: 632-640
Publication/Series: Genes and Immunity
Volume: 13
Issue: 8
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.

Keywords

  • Basic Medicine
  • age
  • association
  • autoimmunity
  • CIITA
  • type 1 diabetes (T1D)
  • major histocompatibility antigen class 2
  • transactivator protein
  • adolescent
  • adult
  • age distribution
  • article
  • controlled study
  • female
  • genetic association
  • genetic risk
  • genetic variability
  • genotype
  • human
  • human tissue
  • insulin dependent diabetes mellitus
  • major clinical study
  • male
  • priority journal
  • Sweden

Other

Published
  • Translational Neurogenetics
  • Diabetes - Cardiovascular Disease
  • ISSN: 1476-5470
  • PMID:23052709
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79

60:11:015

Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00