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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

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.

Detaljer

Författare
  • A Gyllenberg
  • Samina Asad
  • F Piehl
  • L Padyukov
  • B Van Yserloo
  • E A Rutledge
  • B McNeney
  • J Graham
  • C. Graff
  • C Forsell
  • K Åkesson
  • G. Forsander
  • S.A. Ivarsson
  • B. Lindblad
  • J Ludvigsson
  • C Marcus
  • L Alfredsson
  • I Kockum
Enheter & grupper
Externa organisationer
  • Salish Kootenai College
  • Sahlgrenska University Hospital
  • Karolinska Institute
  • Lund University
  • University of Washington, Seattle
  • Simon Fraser University
  • Skåne University Hospital
  • Ryhov County Hospital, Jönköping
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinska grundvetenskaper

Nyckelord

Originalspråkengelska
Sidor (från-till)632-640
Antal sidor9
TidskriftGenes and Immunity
Volym13
Utgivningsnummer8
StatusPublished - 2012
PublikationskategoriForskning
Peer review utfördJa

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