Association of CTLA-4 gene promoter polymorphisms with systemic sclerosis in Iranian population

In a recent study, we were unable to show any association between CTLA-4 exon-1 polymorphism and systemic sclerosis (SSc) in Iranian population. In order to further explore the role of this immune inhibitory gene in SSc development, in the present study, the polymorphisms in the CTLA-4 promoter region (−1722 T/C, −1661 A/G and −318 C/T) were investigated in 83 SSc patients and 166 healthy controls. All genotypes and allele frequencies in patients were significantly different from the control group ( P =0.022 for −1722 T/C, P =0.03 for −1661 A/G and P =0.014 for −318 C/T genotypes). The −1722C, −1661G and −318T alleles contributed to SSc with P =0.012, odds ratio (OR) 2.16, P =0.031, OR 1.82 and P =0.023, OR 2.45, respectively. A significant difference was observed in the frequency homozygous ‘genotype combination’ −1722TT/−1661AA/−318CC of these three polymorphisms ( P c =0.003). The frequency of this genotype combination was significantly higher in the control group than in patients. Results of this investigation indicate that −1722C, −1661G and −318T alleles of CTLA-4 gene promoter appear to be associated with SSc, and individuals carrying these alleles may be more susceptible to this disease.