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Uveitis is a devastating ocular disease that causes blindness. Our previous studies have achieved great advancements in depicting the genetic profiles of uveitis regarding complement pathway genes. This study aimed to provide additional insights into this interest by testing the “central” factor of the complement system,  C3  gene variants, in two uveitis entities. Eight haplotype-tagging SNPs of  C3  gene were genotyped in 141 anterior uveitis (AU), 158 non-infectious intermediate and posterior uveitis (NIPU) and 293 controls. The results showed that none of the tagging SNPs had a significant association with uveitis ( P  > 0.05), either in the global uveitis or subtypes. Although rs428453 showed a nominal association with NIPU subtype in the recessive model ( P  = 0.042), the  P  value could not withstand the Bonferroni correction ( P   corr  > 0.05). Stratification analyses according to HLA-B27 status and correlation analysis still did not find any significant interactions or genetic markers regarding AU. Logistic regression analysis also revealed no gender-related epistatic effects of  C3  on uveitis. Two haplotype blocks were defined across the  C3  locus but neither of them was significantly associated with uveitis or subtypes. This study shows no significant association of the  C3  gene with uveitis, suggesting  C3  confers either no or limited risk for uveitis susceptibility.

Lack of association of C3 gene with uveitis: additional insights into the genetic profile of uveitis regarding complement pathway genes