CTLA-4 gene polymorphisms in patients with Turner syndrome

Abstract

Immunological disturbances have previously been described in Turner syndrome (TS) that were associated with reduced levels of serum IgG and IgM, increased IgA and a decrease of circulating T- and B lymphocytes. The cytotoxic T-lymphocyte antigen 4 (CTLA-4; CD152) is expressed on activated T cells and inhibits further activation by binding to costimulatory molecules B7.1 and B7.2 of antigen-presenting cells. In order to evaluate the role of CTLA-4 gene in TS disease we analysed five single nucleotide polymorphisms (SNPs) within the CTLA-4 gene [MH30 (C/G n=19), -1661 (A/G n=23), -319 (C/T n=23), +49 (A/G=36) and CT60 (G/A n=19)] in patients with TS and in healthy controls (n=167). Additionally, haplotypes in both patients and controls were constructed and compared. The polymorphisms -319, MH30 and -1661 were genotyped by restriction fragment length polymorphisms, the +49 polymorphism by single strand conformation polymorphism and the CT-60 polymorphism by real time PCR. Patients and controls were compared using genotype-wise Chi2. The CTLA4 MH30 (C/G) heterozygosity rate (57.9% vs. 40.1%) was higher in patients with TS than in healthy controls while the variant C was less frequent (5.3% vs. 22.8%). However, the differences did not reach the level of statistical significance (p=0.1). Furthermore, no significant differences in the distribution of the polymorphisms -1661 (A/G), +49 (A/G) CT60 (G/A) and CTLA4–319 (C/T) were observed between TS and healthy controls. Our data suggest that the CTLA-4 MH30 polymorphism could be associated with TS disease whereas the polymorphisms -1661, +49, CT60 and -319 within the CTLA-4 gene are probably not related to the TS disease. An association with CTLA4 variants in a subgroup of TS patients may contribute to the frequently coobserved autoimmune disorders. To confirm this hypothesis the sample size will be increased and functional studies of the CTLA-4 gene performed that are focused on the underlying signal transduction pathway in order to elucidate the role of these SNPs in TS.