Genetic associations in Italian primary sclerosing cholangitis: Heterogeneity across Europe defines a critical role for HLA-C
Copyright policy )Genetic associations in Italian primary sclerosing cholangitis: Heterogeneity across Europe defines a critical role for HLA-C
The HLA complex on chromosome 6p21 is firmly established as a risk locus for primary sclerosing cholangitis (PSC). We aimed to exploit genetic differences between Northern Europe and Italy in an attempt to define a causative locus in this genetic region.Seventy-eight North-Italian PSC patients and 79 controls were included. We performed sequencing-based genotyping of HLA-C, HLA-B, and HLA-DRB1. The major histocompatibility chain-related A (MICA) transmembrane microsatellite was analysed using PCR fragment length determination. The tumour necrosis factor-alpha (TNF-alpha)-308G-->A polymorphism was genotyped with TaqMan. Allele frequencies were compared with Chi-square tests. Uncorrected p-values A. At HLA-DRB1, we confirmed positive and negative associations with DRB1*15 and DRB1*07, respectively, while there were no associations with the DRB1*03, *04 or *1301 alleles typically detected in PSC in Northern Europe.The strong inhibitory of the KIR ligand HLA-C2 protects against PSC development in all populations hitherto studied. Further studies on the role of natural killer cells and T-lymphocytes expressing KIRs in PSC pathogenesis are warranted.
- University of Padua Italy
- Yale University United States
- University of Oslo Norway
- University of Milan Italy
- University of Milano-Bicocca Italy
Adult, Liver Cirrhosis, Male, PBC; HLA-c, Adolescent, Cholangitis, Sclerosing, HLA-C Antigens, Gene Frequency, HLA-C, PSC, primary sclerosing cholangitis, DRB1*03, DRB1*04, DRB1*1301, Humans, Young Adult ; Reference Values ; Cholangitis, Sclerosing ; Gene Frequency ; Humans ; Inflammatory Bowel Diseases ; Aged ; HLA-B Antigens ; Europe ; Liver Cirrhosis ; HLA-C Antigens ; Chromosomes, Human, Pair 6 ; Chromosome Mapping ; Italy ; Risk Assessment ; Microsatellite Repeats ; Aged, 80 and over ; HLA-DR Antigens ; Adult ; Middle Aged; Adolescent ; Male ; Female, Aged, Aged, 80 and over, Chromosome Mapping, HLA-DR Antigens, Inflammatory Bowel Diseases, Europe, Italy, HLA-B Antigens, Chromosomes, Human, Pair 6, Female, HLA-DRB1 Chains, Microsatellite Repeats
Adult, Liver Cirrhosis, Male, PBC; HLA-c, Adolescent, Cholangitis, Sclerosing, HLA-C Antigens, Gene Frequency, HLA-C, PSC, primary sclerosing cholangitis, DRB1*03, DRB1*04, DRB1*1301, Humans, Young Adult ; Reference Values ; Cholangitis, Sclerosing ; Gene Frequency ; Humans ; Inflammatory Bowel Diseases ; Aged ; HLA-B Antigens ; Europe ; Liver Cirrhosis ; HLA-C Antigens ; Chromosomes, Human, Pair 6 ; Chromosome Mapping ; Italy ; Risk Assessment ; Microsatellite Repeats ; Aged, 80 and over ; HLA-DR Antigens ; Adult ; Middle Aged; Adolescent ; Male ; Female, Aged, Aged, 80 and over, Chromosome Mapping, HLA-DR Antigens, Inflammatory Bowel Diseases, Europe, Italy, HLA-B Antigens, Chromosomes, Human, Pair 6, Female, HLA-DRB1 Chains, Microsatellite Repeats
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