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Donaldson, P. et al.

Peter Donaldson, Sivakumar Veeramani, Anna Baragiotta, Annarosa Floreani, Carla Venturi, Simon Pearce, Valerie Wilson, David Jones, Oliver James, John Taylor, Julia Newton, Margaret Bassendine,

Cytotoxic T-lymphocyte-associated antigen-4 single nucleotide polymorphisms and haplotypes in primary biliary cirrhosis.

BACKGROUND & AIMS: Twin and family studies suggest that there is a significant heritable component to primary biliary cirrhosis (PBC). Selected cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) gene polymorphisms have been proposed as nonspecific determinants of disease risk in a variety of autoimmune diseases, including PBC. However, there has been considerable debate over the validity of these associations and the precise location of the disease-promoting polymorphism. METHODS: We investigated 6 single-nucleotide polymorphisms in the CTLA4 gene in a total of 327 PBC patients and 391 healthy controls: 247 patients and 292 controls from the United Kingdom and a further 80 patients and 99 controls from northern Italy. RESULTS: The previously reported association with CTLA4 A+49G was not replicated in the Italian series, and there were no significant differences in the distribution of any of the 6 polymorphisms comparing allele, genotype, or haplotype distribution in patients vs healthy controls in the UK series. Furthermore, there were no significant associations with the clinical variables of histologic stage, portal hypertension, or Mayo score. However, when PBC-40 Fatigue Domain scores were considered, a number of significant trends were noted, but none were significant after correction for multiple testing. Thus, fatigue scores were higher in those with the CTLA4 -319 T allele (P < .05, p corrected not significant) and in those with the CTLA4 +49 AA genotype (P < .05, pc not significant). CONCLUSIONS: Contrary to previous reports the CTLA4 gene is not a major risk factor for PBC, nor is it a major determinant of disease progression.[1]

References

Cytotoxic T-lymphocyte-associated antigen-4 single nucleotide polymorphisms and haplotypes in primary biliary cirrhosis. Donaldson, P., Veeramani, S., Baragiotta, A., Floreani, A., Venturi, C., Pearce, S., Wilson, V., Jones, D., James, O., Taylor, J., Newton, J., Bassendine, M. Clin. Gastroenterol. Hepatol. (2007) [Pubmed]

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