Association of Complement Factor H Tyrosine 402 Histidine Genotype with Posterior Involvement in Sarcoid-Related Uveitis

• Published in: American journal of ophthalmology 2013-06, Vol.155 (6), p.1068-1074.e1
• Main Authors: Thompson, Ian A, Liu, Baoying, Sen, H. Nida, Jiao, Xiadong, Katamay, Robert, Li, Zhiyu, Hu, Mengjun, Hejtmancik, Fielding, Nussenblatt, Robert B
• Format: Article
• Language: English
• Subjects: African Continental Ancestry Group - genetics; Blood banks; Case-Control Studies; Complement Factor H - genetics; Confidence intervals; Deoxyribonucleic acid; Disease; DNA; European Continental Ancestry Group - genetics; Female; Gene Frequency; Genetics; Genotype; Genotype & phenotype; Genotyping Techniques; Histidine; Humans; Macular degeneration; Male; Middle Aged; Neurosciences; Older people; Ophthalmology; Panuveitis - genetics; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Review boards; Sarcoidosis; Sarcoidosis - genetics; Software; Tyrosine; Uveitis, Posterior - genetics
• ISSN: 0002-9394; 1879-1891
• DOI: 10.1016/j.ajo.2013.01.019

Purpose To determine whether the complement factor H ( CFH ) tyrosine 402 histidine (Y402H) variant, recently shown to be associated with age-related macular degeneration (AMD) and multifocal choroiditis, is associated with specific ocular sarcoidosis clinical phenotypes in black and white persons. Design Case-control study. Methods The CFH Y402H polymorphism (rs1061170) was genotyped in 41 subjects with ocular sarcoidosis and 393 control subjects. Allele frequencies in the ocular sarcoidosis cases were compared with controls using chi-square score tests. Genotypic model-based (dominant, recessive, and additive) associations of the rs1061170 allele were tested using multivariate logistic regression. Bayesian information criteria were used to formalize model selection. Genotypes were correlated with disease characteristics and severity of ocular inflammation. Results The C allele (rs1061170) was found in 35% of controls, but occurred with a significantly higher frequency (48.7%) in ocular sarcoidosis cases (odds ratio, 1.72; 95% confidence interval, 1.09 to 2.78; P  = .018). Logistic regression demonstrated an association between rs1061170 and ocular sarcoidosis in 2 of 3 genetic models (additive, P  = .0078; recessive, P  = .0018). Posterior uveitis and panuveitis were overrepresented significantly in cases with the homozygous variant genotype (CC, 91%; P  = .047). The population-attributable risk related to this CFH risk variant was 20%. Conclusions The Y402H polymorphism of CFH seems to be associated with ocular sarcoidosis in black and white persons. Carriage of the CFH Y402H polymorphism in both alleles is associated with an increased risk for posterior uveitis and panuveitis presentation. The prognostic importance of this genotype will require prolonged follow-up studies.