Complement factor H and LOC387715/ARMS2/HTRA1 variant's frequencies and phenotypic associations in neovascular age-related macular degeneration, a pilot study

Abstract

PurposeTo evaluate the frequency of 12 single nucleotide polymorphisms (SNPs) of complement factor H (CFH) and LOC387715/ARMS2/HRTA1 and their association with some of the presenting clinical features of neovascular age-related macular degeneration (AMD).MethodsIn this prospective non-comparative case series forty four naïve patients with neovascular AMD were genotyped using sequencing or Sequenom iPLEX technology. Descriptive tests were used for displaying the magnitude of each allele, gender distribution, and age at diagnosis. Fisher exact test was used to evaluate the correlation between visual acuity (VA) and different alleles. Also Kruskal-Wallis test was used for comparison between age at the time of diagnosis and different alleles.ResultsThe most frequent SNP among studied patients was rs1061147 with 100% frequency rate. The least common was rs2672598 with a frequency of 52.27%. Only the allele rs800292 of CFH locus on 1q32 was associated with VA better than 20/200 (p value = 0.034). The frequency of this allele was 77.27% (34 patients) in this study. There was no significant association between any of alleles, and VA worse than 20/200(p > 0.05). Fifteen patients had bilateral exudative AMD (34.09%). There was no significant difference between alleles in bilateral neovascular AMD and unilateral disease. Also bilateral and unilateral patients were not different in terms of age, gender or VA (p value: 0.330, 0.764 and 0.456 respectively). There was also no significant association between any of SNPs and bilaterality of disease.ConclusionWe designated the frequencies of SNPs of CFH and LOC387715/ARMS2/HRTA1 in neovascular AMD in a sample of Iranian patients. Only the allele rs800292 of CFH locus on chromosome 1q32 was associated with better VA.

Renal and Pulmonary Dense Deposit Disease Presenting as Pulmonary-Renal Syndrome

“… 19 Finally, genetic evaluation revealed 4 genetic variants in the CFH gene, of which 2 (rs1061170 and rs2274700) are previously described in DDD, another (rs35292876) is reported as a silent polymorphism in patients with atypical hemolytic uremic syndrome, and the last (rs1061147) is associated with ocular drusen and age-related macular degeneration. 20 , 21 , 22 , 23 Taken together, the multiple abnormalities of the alternative pathway of complement in our patient encompassing both genetic and acquired components likely resulted in severe activation of alternative pathway of complement with ensuing renal and pulmonary DDD. A limitation of the report is that complete genetic evaluation of other complement-regulating proteins was not performed.…”

Role of complement factor B rs4151667 (L9H) polymorphisms and its interactional role with CFH Y402H and C3 rs2230199 (R102G) risk variants in age-related macular degeneration: a case control study

“…It should be bear in mind that the other genes of the complement system including C3 (rs2230199), CFI (rs141853578), and CFH (rs2274700, rs3753395, rs800292, and rs1061170) had previously studied in this population have shown their association with the disease [17][18][19][20][21][22][23].…”

The effect of complement factor B gene variation on age-related macular degeneration in Iranian patients

“…So far, several genes involved in the complement system such as C3, CFI, and CFH have been studied in samples of the Iranian population in which C3 (rs2230199), CFI (rs141853578), and CFH (rs2274700, rs3753395, rs800292, and rs1061170) genes have shown significant association with AMD in this population 28, 29, 30, 31, 32, 33, 34. Several studies have been conducted on the association of CFB gene variation and AMD.…”