Open AccessDistinctive HLA‐II association with primary biliary cholangitis on the Island of Sardinia
Author(s) -
Clemente Maria Grazia,
Frau Fulvia,
Bernasconi Matilde,
Macis Maria Doloretta,
Cicotto Lucia,
Pilleri Giampaolo,
De Virgiliis Stefano,
Castiglia Paolo,
Farci Patrizia
Publication year - 2017
Publication title -
ueg journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.667
H-Index - 35
eISSN - 2050-6414
pISSN - 2050-6406
DOI - 10.1177/2050640616665030
Subject(s) - haplotype , allele , human leukocyte antigen , medicine , autoimmune hepatitis , allele frequency , population , immunology , gastroenterology , genetics , hepatitis , biology , antigen , gene , environmental health
Background The HLA DRB1 *08 allele associated with primary biliary cholangitis (PBC) among Caucasians is of low frequency in the Sardinian population. Objective The aim of our study was to type a cohort of PBC patients from the island of Sardinia for HLA class II antigens. Methods Twenty Sardinian patients affected by PBC, 14 with autoimmune hepatitis (AIH) and 89 healthy controls (HCs) were typed for HLA class II alleles by dot‐blot analysis. Results The PBC‐associated HLA DRB1 *08 allele was detected in none of the studied individuals. The DRB1 *0301– DQB1 *0201 was the prevalent HLA haplotype, detected in 19 (47.5%) out of 40 PBC haplotypes (OR = 3.0; 95% CI 1.5–6.2) and in 11 (39.3%) out of 28 AIH haplotypes (OR = 2.2; 95% CI 0.94–5.0), but in only 41 (23%) out of 178 HC haplotypes. Moreover, PBC patients showed an increased frequency of homozygosity for the DQB1 *0201 allele (35% compared with 6.7% of the HCs; OR = 7.5; 95% CI 2.2–25.7). The frequency of the DRB1*11 allele in the PBC group was about half of that seen in the Sardinian HCs (7.5% vs 15.7%) ( p = ns). Conclusions Our study confirmed the low frequency of the HLA DRB1 *08 allele among Sardinians, either in the general population or PBC patients. The high prevalence of the HLA DRB1 *0301– DQB1 *0201 haplotype is a distinctive genetic feature of PBC among Sardinians. Our study strengthens the hypothesis that still unknown genetic, epigenetic, and environmental factors must be involved in the pathogenesis of different HLA‐associated liver diseases, and it represents a pathfinder that warrants exploration in a future extensive study.