CTLA-4 gene polymorphisms predispose to autoimmune endocrinopathies but not to celiac disease.

OBJECTIVES: The aim of the study was to determine the association of two CTLA-4 gene polymorphisms (CT60, +49 A/G) with Hashimoto thyroiditis (HT), type 1 diabetes mellitus (T1DM) and celiac disease (CD) as well as with the occurrence of multi-organ involvement by autoimmunity in children.

METHODS: Genotyping was done by RFLP analysis in Slovak children with HT (n=63) and CD (n=120) and both Slovak and Slovene children with T1DM (n=320) and healthy controls (n=231).

RESULTS: We found a significant association of the G allele of the CT60 polymorphism with HT (p<0,0005) in the Slovak population and T1DM in both Slovak (p<0.01) and Slovene populations (p<0.005). The G allele of the +49A/G polymorphism was significantly, though less strongly, associated with T1DM (p<0.05) and HT (p<0.05). Distribution of genotypes of CTLA-4 gene polymorphisms in CD patients did not differ significantly from controls. None of the polymorphisms was associated with multi-organ involvement by autoimmunity.

CONCLUSION: The G allele of both examined CTLA-4 gene polymorphisms predisposes to HT and T1DM, but not to CD. No association with multi-organ involvement was found. The GG genotype of the CT60 polymorphism may identify CD patients at an increased risk for concomitant T1DM and HT. Further studies to assess the predictive value of CTLA-4 polymorphisms for the co-occurrence of HT and T1DM in CD patients are needed.