Extended haplotype of the CTLA-4 Gene within the coeliac patients in the Maltese population

Abstract

CTLA-4 plays a key role in regulating T lymphocyte-mediated inflammatory responses and contains several single-nucleotide polymorphisms (SNPs) known to alter function. The aims of this study were to determine the population frequency of six single nucleotide polymorphisms amongst the Maltese population, to identify association between the SNPs within the CTLA-4 and ICOS genes and to construct a set of haplotypes of the CTLA-4 gene within the coeliac patients' population. In this study 300 random consecutive neonates' samples and 100 samples from coeliac patients were tested for the following CTLA-4 variants: -1722 TIC, -658 CIT, -318 CIT, +49 AlG, CT60 AlG and ICOS IVS+173 TIC. A positive association was shown between the ICOS IVS+173C allele and the coeliac condition [OR (odds ratio) = 1.564, C.1. 1.125-2.174) and a negative correlation (protective effect) was shown for the CT60G allele (OR = 0.640; C.1. 0.460-0.889). An association was shown between the ICOS IVS+173C allele and an older age at diagnosis (OR = 2.24, P = 0.006, C.1. = 1.24-4.03). A similar association was shown with the CTLA-4 -318T allele (OR = 1.86, P = 0.047, C.1. 1.00- 3.46). A protective effect was shown between the CT60G allele and an older age at diagnosis (OR = 0.42, P = 0.02, C.1. 0.20-0.90) as well in both the GIT and non-GIT groups. Moreover an association between the ICOS IVS+173C allele and non-GIT group was noted. Twelve haplotypes were found to constitute 98% of the haplotypes present in the population. A possible protective locus linked with the BI haplotype might be present in the Maltese population whilst a deleterious locus might be present on the 'un-named' (UNN) haplotypes, UNN1 and UNN5. The data obtained in this study further confirms that the functional variation in the CTLA-4 gene predisposes to coeliac disease.