Association of CTLA4 gene polymorphisms with coeliac disease in the Maltese population.

Abstract

Coeliac disease has an autoimmune component in genetically predisposed individuals triggered by an environmental factor (gluten). The disease manifests itself in partial or total villous destruction of the small intestine with consequent malabsorption and malnutrition. The main environmental triggering factor is a transglutaminated peptide within the gliadin component of gluten, which is found in wheat. Coeliac disease has an established HLA component that is responsible to around 35% of the genetic predisposition. The rest of the genetic mechanism is therefore thought to be in the non-HLA region. One hundred coeliac patients were recruited for this study. A high predominance of female over male coeliac patients (3:1, x^2 = 25, p<0.001) was observed amongst the patients. The mean age at diagnosis for the whole group was 34 years (males 32 years, females 34 years, t = -0.65, N.S.). The predominant presenting symptoms were gastrointestinal related. The relatively lower age at diagnosis and the predominance of gastrointestinal symptoms as compared with other foreign studies, suggest that the awareness amongst the general practitioners is relatively low. A higher proportion of males reported a positive family history as compared to females (X2 = 5.44, p =< 0.02 this might be due to a higher reluctance of males to seek medical advice. Two polymorphisms found within the CTLA4 gene were studied amongst a sample of coeliac patients and cord blood DNA samples (n = 187) that acted as the control group. Polymorphisms within the CTLA4 gene have been associated with other autoimmune conditions and the gene plays a very important role in immune-regulatory function. The coeliac individuals and cord blood samples were genotyped for the -318 C/T and +49 AIG single nucleotide polymorphisms. No association of the single polymorphisms or the combined haplotypes with the coeliac condition was apparent amongst the coeliac patients under study. The -318 C allele and the +49 A allele were in linkage disequilibrium amongst the cord blood samples.