title: TNF-alpha polymorphisms in primary biliary cirrhosis: a northern and southern Italian experience.
abstract: Specific HLA alleles and immunoregulatory genes have been evaluated in primary biliary cirrhosis (PBC), but data are discordant. We determined whether TNF-alpha promoter polymorphisms (G-308A and G-238A) and alleles of HLA class II (HLA-DRB1) might be associated either with PBC occurrence and severity in Italian populations from two distinct areas. The distribution of TNF1 (G/G) genotype did not differ either between patients and controls or between patients from Northern and Southern Italy. Contrariwise, the HLA-DRB1*08 appeared positively linked to the occurrence of disease (8.4% in patients vs. 2.5% in controls, P = 0.003), whereas the HLA-DRB1*13 appeared to be protective, being more frequent in controls (12.8%) than in patients (7%) (P = 0.038). Neither positively nor negatively associated alleles of the two genomic loci had an effect on disease progression. We report a distinct genetic risk of developing PBC in the Italian population, with no interaction between the HLA and TNF alleles.
authors.affiliation: Division of Gastroenterology, Casa Sollievo Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy.
authors.forename: Grazia Anna
authors.initials: GA
authors.lastname: Niro
authors.forename: Francesca
authors.initials: F
authors.lastname: Poli
authors.forename: Angelo
authors.initials: A
authors.lastname: Andriulli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bianchi
authors.forename: Francesca
authors.initials: F
authors.lastname: Bernuzzi
authors.forename: Lisa
authors.initials: L
authors.lastname: Caliari
authors.forename: Rosanna
authors.initials: R
authors.lastname: Fontana
authors.forename: Domenica
authors.initials: D
authors.lastname: Gioffreda
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Valvano
authors.forename: Mauro
authors.initials: M
authors.lastname: Podda
authors.forename: Pietro
authors.initials: P
authors.lastname: Invernizzi
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005843:Geography; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007558:Italy; D008105:Liver Cirrhosis, Biliary / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D014409:Tumor Necrosis Factor-alpha