Association of CD59 and CFH polymorphisms with acute anterior uveitis in Chinese population

Abstract

PurposeCD59 complement regulator and complement factor H (CFH) have important roles in complement activation pathways, which are known to affect the development of uveitis. The present study was performed to investigate whether an association exists between CD59 and CFH genetic polymorphisms and acute anterior uveitis (AAU).MethodsA total of 600 individuals (300 patients diagnosed with AAU and 300 healthy controls) were recruited for this case-control study. Five single-nucleotide polymorphisms (SNPs) in CD59 (rs831626, rs12272807, rs831625, rs11585, and rs12576440) and CFH-rs1065489 were genotyped using Sequenom MassARRAY technology. Allele and genotype frequencies were statistically compared between patients and controls using χ test. Analyses were stratified for gender, human leukocyte antigen (HLA)-B27, and ankylosing spondylitis (AS) status.ResultsNo significant association was found between any of the six polymorphisms and AAU. In HLA-B27-negative AAU patients, the frequencies of the G allele and GG homozygosity were lower in CD59-rs831626 when compared with controls (P=0.032). There were also significant decreases in the frequencies of T allele and TT homozygosity in CFH-rs1065489 in AAU patients with AS compared with controls (P=0.002). Furthermore, the frequencies of the T allele and TT homozygosity in CFH-rs1065489 were lower in the AAU male patients with AS compared with controls (P=0.015).ConclusionOur results revealed that SNPs CD59-rs831626 and CFH-rs1065489 were associated with the susceptibility of AAU. The influence on AAU could be gender specific and dependent on the HLA-B27 and AS status. No positive results were found in the overall group.

Genetic profiling of ocular inflammation: further evidence for a gender-specific association of C5 with uveitis

“…Of them, variants in the CFH, CFB and CFI involved in the alternative pathway, were identified as genetic risk markers for various uveitis subtypes [16][17][18][19][20]. A recent report from our laboratory also demonstrated that the classical pathway gene, C1INH, as well as the central component of the cascade, C3 gene, may confer either no or limited risk for uveitis susceptibility [21,22]. Overall, our findings together suggest that the alternative pathway as well as the "upstream" cascade of complement system confers major genetic impact on uveitis susceptibility.…”

“…Our research team have made great efforts in depicting the genetic profile of uveitis and intraocular inflammation regarding complement pathway genes, several genes have been extensively investigated and identified to be associated with many forms of uveitis, these genes included complement factor H (CFH), complement factor B (CFB), complement factor I (CFI), and CD59 [15][16][17][18][19][20]. Meanwhile, we have largely ruled out the involvement of some complement factors in the disease genetics, such as component 1 inhibitor (C1INH), and complement component 3 (C3) [21,22]. Notably, some genetic associations between AU and complement genes were also found in NIPU patients in our study cohort, suggesting that these two uveitis entities shared general genetic background although presenting different clinical phenotypes.…”

CFI-rs7356506 is a genetic protective factor for acute anterior uveitis in Chinese patients

“…Recent reports described that polymorphisms in CFB and CFH specifically associated with anterior uveitis 9 10 . CFB and CFH are immunological factors involved in the complement cascade.…”

“…Moreover, recent studies have reported that immunological factors involved in the complement cascade were associated with AAU, with polymorphisms in complement factors B and H ( CFB ) and ( CFH ), specifically associated with anterior uveitis 9 10 . CFB and CFH are key regulators in the complement pathway, sharing the same binding site for C3b, the larger of two elements formed by the cleavage of complement component 3 (C3) 11.…”

CFHR2‐rs2986127 as a genetic protective marker for acute anterior uveitis in Chinese patients

“…The levels of CC chemokine ligand (CCL) 2, CCL5, and their receptors have been associated with AAU inflammation severity . Moreover, the influence of genetic polymorphisms on uveitis might depend on HLA‐B27 status . Furthermore, only a few studies have noted the relationship between the immune factors and AAU development.…”