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Ian A. Thompson, Baoying Liu, Xiadong Jiao, Nida Sen, Robert Katamay, Mengjun Hu, Fielding Hejtmancik, Robert B. Nussenblatt; CFH and HTRA1 risk alleles in Caucasian and African American ocular sarcoidosis patients. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4163.
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AMD is the leading cause of irreversible blindness in the elderly. Genome-wide association studies have identified common variants including those in the genes encoding complement factor H (CFH Y402H) and high-temperature requirement A-1 (HTRA1 rs11200638) which are associated with an increased risk of AMD. Causal pathways underlying AMD are not fully understood, but current evidence suggests that anomalies in inflammatory immune responses may facilitate progression of macular degeneration towards advanced disease. Thus, the pathogenesis of AMD may share features with other intraocular inflammatory diseases. We aimed to determine if there is an association between these specific risk variants in the CFH and HTRA1 genes and ocular sarcoidosis.
A cohort of 48 patients with diagnosis of ocular sarcoidosis based on clinical exam and 310 disease-free control subjects were enrolled in this case-control study. Genomic DNA was extracted from blood leukocytes. Genotyping for single-nucleotide polymorphisms Y402H in CFH and rs11200638 in HTRA1 was performed using a polymerase chain reaction (PCR) method followed by direct sequencing. Allele and genotype frequencies were analyzed by the Fisher’s exact test.
All the genotypic and allelic frequencies in patients with ocular sarcoidosis and disease-free controls were in Hardy-Weinberg equilibrium. The frequency of the CFH Y402H allele was significantly increased in the ocular sarcoidosis (0.46) patients as compared to disease-free controls (0.35) (p=.047, OR=2.21, 95%CI 1.08 to 4.51). In Caucasians, there was a clear increase in the frequency of CFH Y402H allele (0.58) as compared to race-matched controls (0.36) (p=.004, OR=6.13, 95%CI 1.92 to 19.59). No significant association was found between CFH Y402H and African American ocular sarcoidosis patients overall. However, for both Caucasian and African American cohorts, the CFH variant was strongly associated with ocular sarcoidosis in male patients (p=.0003, OR=7.31, 95% CI 2.60 to 20.53). In Caucasian males, the CFH risk allele frequency was 0.69 in cases compared to 0.34 in controls (p=.002, OR=11.27 95% 2.47 to 51.51). In African American males, the CFH risk allele frequency was 0.65 in cases versus 0.35 in controls (p=.043, OR=4.87, 95%CI 1.13 to 21.00). Genotypic and allelic frequencies of HTRA1 were not different for ocular sarcoidosis patients and controls.
Our data suggest CFH Y402H as a possible novel risk factor for ocular sarcoidosis in Caucasian and African American males. The CFH Y402H variant may not be specific to AMD and may confer significant risk for other intraocular inflammatory diseases. Further confirmation of these findings will need to be addressed in larger studies.
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