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Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis
- Source :
- Genes and immunity, Genes and Immunity; Vol 13
- Publication Year :
- 2012
-
Abstract
- Susceptibility to primary biliary cirrhosis (PBC) is strongly associated with human leukocyte antigen (HLA)-region polymorphisms. To determine if associations can be explained by classical HLA determinants, we studied Italian, 676 cases and 1440 controls, genotyped with dense single-nucleotide polymorphisms (SNPs) for which classical HLA alleles and amino acids were imputed. Although previous genome-wide association studies and our results show stronger SNP associations near DQB1, we demonstrate that the HLA signals can be attributed to classical DRB1 and DPB1 genes. Strong support for the predominant role of DRB1 is provided by our conditional analyses. We also demonstrate an independent association of DPB1. Specific HLA-DRB1 genes (*08, *11 and *14) account for most of the DRB1 association signal. Consistent with previous studies, DRB1*08 (P=1.59 × 10(-11)) was the strongest predisposing allele, whereas DRB1*11 (P=1.42 × 10(-10)) was protective. Additionally, DRB1*14 and the DPB1 association (DPB1*03:01; P=9.18 × 10(-7)) were predisposing risk alleles. No signal was observed in the HLA class 1 or class 3 regions. These findings better define the association of PBC with HLA and specifically support the role of classical HLA-DRB1 and DPB1 genes and alleles in susceptibility to PBC.Genes and Immunity advance online publication, 10 May 2012; doi:10.1038/gene.2012.17.
- Subjects :
- AUTOIMMUNITY
PRIMARY BILIARY CIRRHOSIS
genetic risk
imputation
0302 clinical medicine
Primary biliary cirrhosis
Gene Frequency
MED/12 - GASTROENTEROLOGIA
immune system diseases
Risk Factors
Genetic risk
skin and connective tissue diseases
HLA-DRB1
Genetics (clinical)
HLA-DP beta-Chains
Oligonucleotide Array Sequence Analysis
Genetics
0303 health sciences
Liver Cirrhosis, Biliary
antigen binding pocket
Italy
HLA-DRB1 Chain
030211 gastroenterology & hepatology
Case-Control Studie
antigen-binding pocket
Human
musculoskeletal diseases
risk allele
European Continental Ancestry Group
Immunology
Autoimmune Diseases
autoimmune disease
Biology
Polymorphism, Single Nucleotide
White People
Article
03 medical and health sciences
medicine
Humans
Genetic Predisposition to Disease
Allele
030304 developmental biology
Autoimmune disease
Oligonucleotide Array Sequence Analysi
Risk Factor
HLA polymorfism, PBC, HLA-DRB1, HLA-DPB1
Hla association
medicine.disease
HLA-DP beta-Chain
Case-Control Studies
Risk allele
Imputation (genetics)
Genome-Wide Association Study
HLA-DRB1 Chains
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Genes and immunity, Genes and Immunity; Vol 13
- Accession number :
- edsair.doi.dedup.....8f45b1e10072c24202dd413e2604f5e7