<i>CFI</i>-rs7356506 is a genetic protective factor for acute anterior uveitis in Chinese patients

Huang, Xiu‐Feng; Yang, Mingming; Cai, Wei-Jun; Zheng, Meiqin; Mao, Guangyun; Pang, Chi‐Pui; Jin, Zi‐Bing

doi:10.1136/bjophthalmol-2014-305296

Cited by 16 publications

(18 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As described above, CFH -rs1065489 and CFB -rs1048709 were identified as clinical markers associated with a specific disease phenotype. Moreover, joint effects between their risk genotypes conferring a strongly increased risk to uveitis were also found 17–20, 23 . The molecular mechanism might be affecting the binding affinity with C3b and subsequently disturbing the activation of the alternative pathway C3-convertase (C3bBb).…”

Section: Discussionmentioning

confidence: 87%

“…We further demonstrated that genetic variants of CFB and CFI , in the same complement alternative pathway, are risk factors for both AU and NIPU patients. Moreover, a significant joint-effect among these genes, as well as genotype and phenotype correlations was observed 17, 20, 23 . In addition, parallel studies also demonstrated that genetic variants involved in the alternative pathway, CFH and CFB , as well as C5 , considered as the “downstream” complement regulator, were also associated with type 2 diabetic retinopathy (T2DM), viewed from the perspective of inflammation 16, 22 .…”

Section: Introductionmentioning

confidence: 89%

See 1 more Smart Citation

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

Yang

Wang

Dong

et al. 2017

Sci Rep

View full text Add to dashboard Cite

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.Uveitis is a group of heterogeneous ocular inflammatory diseases with complex phenotypes, which is considered as a substantial visual impairment as well as an important socio-economic problem, being the fourth cause of blindness worldwide 1, 2 . Uveitis can be frequently classified into anterior uveitis (AU), intermediate uveitis (IU), posterior uveitis (PU), and panuveitis according to the anatomical location of the inflammation 3 . AU, which refers to inflammation of the iris and ciliary body, is the most common form found in clinics. Although less common than AU, non-infectious intermediate and posterior uveitis (NIPU) typically is either idiopathic and comprises many well-defined uveitic ocular conditions or associated with systemic underlying autoimmune disorders, including Vogt-Koyanagi-Harada disease (VKH), Behçet's disease (BD), and sarcoidosis 3,4 .Although the exact pathogenesis of uveitis remains unclear, it is generally accepted as an inflammatory condition and mainly mediated by various endogenous immunological mechanisms 5 . Moreover, genetic factors in the initiation and development of uveitis have been recognized for a few decades [6][7][8][9][10][11] .The complement system is a key component of innate immunity and plays an important role in modulating various immune and inflammatory responses. The activation of the complement system occurs along three routes -the classical, alternative, and lectin pathways 12 . Notably, in recent years, accumulating studies have provided increasing evidence that complement is involved in the pathogenesis of uveitis. These studies revealed that activation of the complement system is critical for the develo...

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 89%

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

Yang

Wang

Dong

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Several complement genes were extensively investigated, particular attention was paid on the "upstream" functional pathways. 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].…”

Section: Discussionmentioning

confidence: 94%

“…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].…”

Section: Introductionmentioning

confidence: 99%

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

Yang¹,

Wang²,

Liu³

et al. 2018

Oncotarget

View full text Add to dashboard Cite

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. www.impactjournals.com/oncotarget/

show abstract

“…Several genetic studies have shown that polymorphisms within the complement system can affect immune‐related disease development, including how CFH, complement factor I (CFI) and complement factor B appear to be associated with anterior uveitis . CFI, which is a serine protease in the complement cascade, also appears to be associated with AAU . CFHR genes are strongly associated with different diseases involving complement dysregulation, which suggests that they play a major role in regulating complement activation through protein production .…”

Section: Introductionmentioning

confidence: 99%

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

Huang

Wang

et al. 2016

The Journal of Gene Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

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

Abstract: This study has revealed a significant association between AAU and CFI-rs7356506, suggesting that CFI is involved in the pathogenesis of AAU, and that its influence on AAU may differ depending on gender and HLA-B27 status.

Cited by 16 publications

References 26 publications

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

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

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

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

Contact Info

Product

Resources

About