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

Gyllenberg, A; Asad, Samina; Piehl, F; Swanberg, Maria LU ; Padyukov, L; Van Yserloo, B; Rutledge, E A; McNeney, B; Graham, J and Orho-Melander, Marju LU , et al. (2012) In Genes and Immunity 13(8). p.632-640
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... (More)
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. (Less)
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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
in
Genes and Immunity
volume
13
issue
8
pages
9 pages
publisher
Nature Publishing Group
external identifiers
  • wos:000312000700004
  • other:PMID:23052709
  • scopus:84870882497
ISSN
1476-5470
DOI
10.1038/gene.2012.44
language
English
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yes
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4dd371f3-f2b2-4c78-80ec-4ac41f7fd18e (old id 3224398)
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http://www.ncbi.nlm.nih.gov/pubmed?term=Age-dependent%20variation%20of%20genotypes%20in%20MHC%20II%20transactivator%20gene%20(CIITA)%20in%20controls%20and%20association%20to%20type%201%20diabetes.
date added to LUP
2012-12-07 10:16:45
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2017-11-14 12:39:17
@article{4dd371f3-f2b2-4c78-80ec-4ac41f7fd18e,
  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.},
  author       = {Gyllenberg, A and Asad, Samina and Piehl, F and Swanberg, Maria and Padyukov, L and Van Yserloo, B and Rutledge, E A and McNeney, B and Graham, J and Orho-Melander, Marju and Lindholm, E. and Graff, C. and Forsell, C and Åkesson, K and Landin-Olsson, Mona and Forsander, G. and Ivarsson, S.A. and Larsson, H. and Lindblad, B. and Ludvigsson, J and Marcus, C and Lernmark, Åke and Alfredsson, L and Åkesson, Kristina and Kockum, I and Carlsson, Annelie},
  issn         = {1476-5470},
  keyword      = {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},
  language     = {eng},
  number       = {8},
  pages        = {632--640},
  publisher    = {Nature Publishing Group},
  series       = {Genes and Immunity},
  title        = {Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes},
  url          = {http://dx.doi.org/10.1038/gene.2012.44},
  volume       = {13},
  year         = {2012},
}