TNF-alpha polymorphisms in primary biliary cirrhosis: a northern and southern Italian experience.
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.
Niro
Grazia Anna
GA
Division of Gastroenterology, Casa Sollievo Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy.
Poli
Francesca
F
Andriulli
Angelo
A
Bianchi
Ilaria
I
Bernuzzi
Francesca
F
Caliari
Lisa
L
Fontana
Rosanna
R
Gioffreda
Domenica
D
Valvano
Maria Rosa
MR
Podda
Mauro
M
Invernizzi
Pietro
P
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*
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D014409:Tumor Necrosis Factor-alpha