Research Papers: Immunology:
Genetic profiling of ocular inflammation: further evidence for a genderspecific association of C5 with uveitis
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Ming Ming Yang1, Xiao Yuan Wang1, Ying Wei Liu2, Li Dong1, De Ju Kong1, Hong Yan Sun1, Jiao Jie Fan1, Xu Hui Yu1, and Jun Wang3
1Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, China
2Department of Ophthalmology, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, China
3Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
Correspondence to:
Jun Wang, email: [email protected]
Keywords: complement system; C5; ocular inflammation; uveitis; molecular genetics
Received: September 19, 2017 Accepted: February 13, 2018 Published: February 17, 2018
ABSTRACT
Objective: Uveitis is a major cause for visual impairment, our previous studies have made significant advancements in depicting the genetic profile of complement genes in uveitis. This study aimed to further investigate whether the terminal pathway gene, Complement component 5 (C5), confers susceptibility to uveitis.
Methods: Six tagging SNPs in C5 were genotyped in 592 unrelated study subjects: 141 anterior uveitis patients, 158 patients with non-infectious intermediate and posterior uveitis, and 293 controls. Multiple in-depth analyses have been conducted.
Results: Among the six C5 SNPs, rs17611 was significantly associated with uveitis after adjusted for gender and SNP-gender interaction (P = 0.017). After stratification by gender, rs17611 G allele and GG homozygosity confers an increased risk for uveitis in males (P = 0.004, OR = 1.67 and P = 0.009, OR = 2.69, respectively) but not in females. Moreover, genotype-phenotype correlation analysis revealed an association between rs17611 and disease recurrence (P = 0.045). The haplotype GC, defined by rs17611 and rs2269066, was also found to be associated with total uveitis and specific intermediate and posterior uveitis subtype (P = 0.0055, OR = 1.51 and P = 0.0084, OR = 1.58, respectively). Other polymorphisms were not significantly associated with either investigated uveitis entities.
Conclusions: This study shows a gender-specific association of C5-rs17611 with uveitis, indicating that C5 may have an epistatic effect with gender in the pathogenesis of uveitis. This study help us depict the disease profile and estimate the contribution of each complement activation pathway in ocular immunologic process.