PMID- 19295542
OWN - NLM
STAT- MEDLINE
DCOM- 20090828
LR  - 20090603
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Linking)
VI  - 10
IP  - 4
DP  - 2009 Jun
TI  - Reproducible association with type 1 diabetes in the extended class I region of 
      the major histocompatibility complex.
PG  - 323-33
LID - 10.1038/gene.2009.13 [doi]
AB  - The high-risk human leukocyte antigen (HLA)-DRB1, DQA1 and DQB1 alleles cannot 
      explain the entire type 1 diabetes (T1D) association observed within the extended 
      major histocompatibility complex. We have earlier identified an association with 
      D6S2223, located 2.3 Mb telomeric of HLA-A, on the 
      DRB1(*)03-DQA1(*)0501-DQB1(*)0201 haplotype, and this study aimed to fine-map the 
      associated region also on the DRB1(*)0401-DQA1(*)03-DQB1(*)0302 haplotype, 
      characterized by less extensive linkage disequilibrium. To exclude associations 
      secondary to DRB1-DQA1-DQB1 haplotypes, 205 families with at least one parent 
      homozygous for these loci, were genotyped for 137 polymorphisms. We found novel 
      associations on the DRB1(*)0401-DQA1(*)03-DQB1(*)0302 haplotypic background with 
      eight single nucleotide polymorphisms (SNPs) located within or near the PRSS16 
      gene. In addition, association at the butyrophilin (BTN)-gene cluster, 
      particularly the BTN3A2 gene, was observed by multilocus analyses. We replicated 
      the associations with SNPs in the PRSS16 region and, albeit weaker, to the BTN3A2 
      region, in an independent material of 725 families obtained from the Type 1 
      Diabetes Genetics Consortium. It is important to note that these associations 
      were independent of the HLA-DRB1-DQA1-DQB1 genes, as well as of associations 
      observed at HLA-A, -B and -C. Taken together, our results identify PRSS16 and 
      BTN3A2, two genes thought to play important roles in regulating the immune 
      response, as potentially novel susceptibility genes for T1D.
FAU - Viken, M K
AU  - Viken MK
AD  - Institute of Immunology, Faculty Division Rikshospitalet, University of Oslo, 
      Oslo, Norway.
FAU - Blomhoff, A
AU  - Blomhoff A
FAU - Olsson, M
AU  - Olsson M
FAU - Akselsen, H E
AU  - Akselsen HE
FAU - Pociot, F
AU  - Pociot F
FAU - Nerup, J
AU  - Nerup J
FAU - Kockum, I
AU  - Kockum I
FAU - Cambon-Thomsen, A
AU  - Cambon-Thomsen A
FAU - Thorsby, E
AU  - Thorsby E
FAU - Undlien, D E
AU  - Undlien DE
FAU - Lie, B A
AU  - Lie BA
LA  - eng
GR  - U01 DK062418/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090319
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (Histocompatibility Antigens Class I)
RN  - EC 3.4.21.- (PRSS16 protein, human)
RN  - EC 3.4.21.- (Serine Endopeptidases)
SB  - IM
MH  - Alleles
MH  - Diabetes Mellitus, Type 1/*genetics/immunology
MH  - Female
MH  - Gene Frequency/genetics
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - Haplotypes
MH  - Histocompatibility Antigens Class I/*genetics/immunology
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Male
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Serine Endopeptidases/*genetics
EDAT- 2009/03/20 09:00
MHDA- 2009/08/29 09:00
CRDT- 2009/03/20 09:00
PHST- 2009/03/20 09:00 [entrez]
PHST- 2009/03/20 09:00 [pubmed]
PHST- 2009/08/29 09:00 [medline]
AID - gene200913 [pii]
AID - 10.1038/gene.2009.13 [doi]
PST - ppublish
SO  - Genes Immun. 2009 Jun;10(4):323-33. doi: 10.1038/gene.2009.13. Epub 2009 Mar 19.