Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes
2012 (English)In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 13, no 8, 632-640 p.Article in journal (Refereed) Published
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 x 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.
Place, publisher, year, edition, pages
Nature Publishing Group , 2012. Vol. 13, no 8, 632-640 p.
type 1 diabetes (T1D), CIITA, autoimmunity, association, age
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-86896DOI: 10.1038/gene.2012.44ISI: 000312000700004OAI: oai:DiVA.org:liu-86896DiVA: diva2:583034
Funding Agencies|Juvenile Diabetes Research Foundation International|2-2000-5701-2001-873|Swedish Research Council||Swedish Diabetes Foundation (Svenska Diabetes Fonden)||Swedish Child Diabetes Foundation (Barndiabetes Fonden)||Novo Nordisk Foundation||Magnus Bergvalls Foundation||NIH|DK-17047|Swedish Brain Power initiative||Gun and Bertil Stohnes Foundation||Foundation for Old Servants||Alzheimer Foundation||LIONS Foundation for Research of Age Related Disorders||AFA foundation||Soderberg Foundation||Knut and Alice Wallenbergs Foundation||Neuropromise|LSHM-CT-2005-018637|2013-01-072013-01-072013-01-07