Association of CTLA-4 exon 1(+49 A/G) polymorphism and susceptibility to SLE in Egyptian children and adolescents

Background Recently, Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene has emerged as an attractive candidate gene implicated in susceptibility to autoimmune disease such as Juvenile-onset SLE (JSLE). Objective To investigate CTLA-4 exon 1 + 49A/G (rs231775) SNP as a genetic marker for susceptibility to JSLE and lupus nephritis in Egyptian children and adolescents. Methods This prospective case-control study included 260 patients diagnosed with Juvenile-onset SLE, and 260 healthy controls. We genotyped all participants for CTLA-4 (A/G) (rs231775) SNP located in exon 1 at position 49 by polymerase chain reaction. Results The CTLA-4 exon 1 + 49 G/G gene variant and G allele were significantly more represented in JSLE patients than healthy controls (27% vs 8%; ORs = 4.2; [95% CI: 2.4 – 7.3]; for the G/G genotype) and (47.5% vs 35%; ORs: 1.7; [95% CIs: 1.3 – 2.2] ; for G allele); P < .01. The CTLA-4 G/G genotype and G allele were identified as possible risk factors for development of lupus nephritis (for G/G genotype; ORs: 5.09; [95% CIs: 1.7 - 13.9]; P = .0001, and for G- allele; ORs: 2.4; [95% CIs: 1.5 - 3.78]; P = .004). Conclusion The CTLA-4 exon 1 + 49 A/G polymorphism may confer susceptibility to Juvenile-onset SLE. Moreover, CTLA-4 G/G genotype and G allele at exon 1 + 49 may constitute independent risk factors for development of lupus nephritis in Egyptian children and adolescents.