PMID- 20054343
OWN - NLM
STAT- MEDLINE
DCOM- 20100820
LR  - 20211020
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Print)
IS  - 1466-4879 (Linking)
VI  - 11
IP  - 3
DP  - 2010 Apr
TI  - Genetic variation within the HLA class III influences T1D susceptibility 
      conferred by high-risk HLA haplotypes.
PG  - 209-18
LID - 10.1038/gene.2009.104 [doi]
AB  - Human leukocyte antigen (HLA) class II DRB1 and DQB1 represent the major type I 
      diabetes (T1D) genetic susceptibility loci; however, other genes in the HLA 
      region are also involved in T1D risk. We analyzed 1411 pedigrees (2865 affected 
      individuals) from the type I diabetes genetics consortium genotyped for HLA 
      classical loci and for 12 single-nucleotide polymorphisms (SNPs) in the class III 
      region previously shown to be associated with T1D in a subset of 886 pedigrees. 
      Using the transmission disequilibrium test, we compared the proportion of SNP 
      alleles transmitted from within the high-risk DR3 and DR4 haplotypes to affected 
      offspring. Markers rs4151659 (mapping to CFB) and rs7762619 (mapping 5' of LTA) 
      were the most strongly associated with T1D on DR3 (P=1.2 x 10(-9) and P=2 x 
      10(-12), respectively) and DR4 (P=4 x 10(-15) and P=8 x 10(-8), respectively) 
      haplotypes. They remained significantly associated after stratifying individuals 
      in analyses for B*1801, A*0101-B*0801, DPB1*0301, DPB1*0202, DPB1*0401 or 
      DPB1*0402. Rs7762619 and rs4151659 are in strong linkage disequilibrium (LD) 
      (r(2)=0.82) with each other, but a joint analysis showed that the association for 
      each SNP was not solely because of LD. Our data support a role for more than one 
      locus in the class III region contributing to risk of T1D.
FAU - Valdes, A M
AU  - Valdes AM
AD  - King's College London, Department of Twin Research and Genetic Epidemiology, UK. 
      ana.valdes@kcl.ac.uk <ana.valdes@kcl.ac.uk>
FAU - Thomson, G
AU  - Thomson G
FAU - Barcellos, L F
AU  - Barcellos LF
LA  - eng
GR  - U01 DK062418/DK/NIDDK NIH HHS/United States
GR  - ABD N01-AI-40076/AI/NIAID NIH HHS/United States
GR  - N01AI40076/AI/NIAID NIH HHS/United States
GR  - U01 DK062418-01/DK/NIDDK NIH HHS/United States
GR  - HHSN266200400076C/PHS HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100107
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Family Health
MH  - Female
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - Genetic Variation
MH  - HLA Antigens/*genetics
MH  - *Haplotypes
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Male
MH  - Pedigree
MH  - *Polymorphism, Single Nucleotide
MH  - Risk Factors
PMC - PMC2858242
MID - NIHMS147982
COIS- Conflict of Interest The authors declare no conflict of interest.
EDAT- 2010/01/08 06:00
MHDA- 2010/08/21 06:00
PMCR- 2010/10/01
CRDT- 2010/01/08 06:00
PHST- 2010/01/08 06:00 [entrez]
PHST- 2010/01/08 06:00 [pubmed]
PHST- 2010/08/21 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - gene2009104 [pii]
AID - 10.1038/gene.2009.104 [doi]
PST - ppublish
SO  - Genes Immun. 2010 Apr;11(3):209-18. doi: 10.1038/gene.2009.104. Epub 2010 Jan 7.