Maria Grazia Clemente1,2, Fulvia Frau1, Matilde Bernasconi3, Maria Doloretta Macis1, Lucia Cicotto1, Giampaolo Pilleri3, Stefano De Virgiliis1, Paolo Castiglia4, Patrizia Farci5,6. 1. Department of Biomedical Sciences and Biotechnologies, University of Cagliari, Cagliari, Italy. 2. Present address: Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari, Italy. 3. 2nd Division of Medicine, Azienda Ospedaliera Brotzu, Cagliari, Italy. 4. Department of Biomedical Sciences, University of Sassari, Sassari, Italy. 5. Department of Medical Sciences "Mario Aresu", University of Cagliari, Cagliari, Italy. 6. Present address: Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Abstract
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.
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.
Authors: Carlo Selmi; Marlyn J Mayo; Nancy Bach; Hiromi Ishibashi; Pietro Invernizzi; Robert G Gish; Stuart C Gordon; Harlan I Wright; Bruce Zweiban; Mauro Podda; M Eric Gershwin Journal: Gastroenterology Date: 2004-08 Impact factor: 22.682
Authors: Pietro Invernizzi; Carlo Selmi; Francesca Poli; Sara Frison; Annarosa Floreani; Domenico Alvaro; Piero Almasio; Floriano Rosina; Marco Marzioni; Luca Fabris; Luigi Muratori; Lihong Qi; Michael F Seldin; M Eric Gershwin; Mauro Podda Journal: Hepatology Date: 2008-12 Impact factor: 17.425