CTLA-4 gene polymorphism confers susceptibility to primary biliary cirrhosis
Section snippets
Materials and Methods
Genotyping was performed on 200 Caucasoid PBC patients from North East England (mean age 64.2±12.4 years, sex ratio 8.5 female: 1 male) and 200 geographically matched normal Caucasoid controls. All patients fulfilled standard diagnostic criteria for PBC (positive antimitochondrial antibody (titre >1:40 by indirect immunofluorescence), cholestatic liver function tests and compatible or diagnostic liver histology). All patients gave informed consent and were enrolled from the Freeman Hospital PBC
Results
The CTLA-4 genotype A/A was seen in markedly fewer PBC patients (57/200-28.5%) than controls (99/200-49.5%). 106/200 (53%) PBC patients and 80/200 (40%) controls were heterozygotes (A/G genotype), whilst 37/200 (18.5%) PBC patients and 21/200 (10.5%) controls were homozygous for the G/G genotype, demonstrating a significant overrepresentation of the G/A and G/G genotypes in PBC patients, χ2=19.4, p=0.00006 (Table 1). The frequencies for the CTLA-4 codon 17 Ala allele (G at position 49) were PBC
Discussion
In this study, the largest population-based case-control study in PBC to date, we have investigated a polymorphism in exon 1 of the CTLA-4 gene as a candidate disease susceptibility locus. We have demonstrated that patients with PBC have significantly more Ala alleles at codon 17 (G-carrying genotypes) than geographically matched controls. This association remained as strong when patients with co-existent clinical autoimmune thyroid disease and thyroid autoantibodies were excluded from
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2014, Egyptian Journal of Medical Human GeneticsCitation Excerpt :An A/G polymorphism in the first exon of CTLA-4 results in an amino acid change (Thr/Ala). The presence of an alanine at codon 17 of CTLA-4 has been associated with susceptibility to type 1 diabetes, autoimmune thyroiditis, systemic lupus erythematosis, celiac disease and biliary cirrhosis [19–21]. However there is a marked controversy about its effect on type 1 diabetes.