An association of neovascular age‐related macular degeneration with polymorphisms of CFH, ARMS2, HTRA1 and C3 genes in Czech population

Abstract

PurposeWe investigated associations between neovascular age‐related macular degeneration (AMD) and rs10490924 polymorphism of ARMS2 gene (age‐related maculopathy susceptibility 2), rs1061170 polymorphism of gene for complement factor H (CFH), rs2230199 polymorphism of gene for complement component C3 and rs11200638 polymorphism of gene for serine protease high‐temperature requirement A1 (HTRA1) in the Czech population.MethodsWe analysed samples of DNA from 307 patients diagnosed with neovascular form of late AMD (average age: 73.7 ± 7.7 years) and 191 control subjects, recruited from patients awaiting cataract surgery (average age, 73.6 ± 8.7 years).ResultsHTRA1, CFH and ARMS2 genes polymorphisms were found to be related to neovascular AMD in the Czech population. All analysed polymorphisms were statistically significantly associated with neovascular AMD, with stronger associations in females than in males. In whole group, CC genotype of CFH gene polymorphism, TT genotype of ARMS2 gene polymorphism and AA genotype of HTRA1 gene polymorphism showed the greatest risk for neovascular AMD with odds ratios equal to 8.43, 10.07, 9.83, respectively (p < 0.0001). Only CG polymorphism of C3 gene showed statistically significant risk for neovascular AMD. In addition, we observed an association between waist circumference and neovascular AMD in both sexes, which further suggests the significance of excessive abdominal fat as a risk factor of AMD. We found a statistically significant association between polymorphisms in HTRA1, CFH and ARMS2 genes and neovascular AMS in the Czech population. The association was stronger in females than in males.ConclusionWe demonstrated a relationship between neovascular AMD and genes for HTRA1, CFH, ARMS2 and C3 in Czech population. To our knowledge, the relationship between these polymorphisms and neovascular AMD in Czech population has never been investigated before.

Association of the HtrA1 rs11200638 Polymorphism with Neovascular Age-Related Macular Degeneration in Indonesia

“…People with the AA genotype had a 20-fold increased risk of having nAMD than those with the GG genotype. This finding is similar to results from other studies in other ethnic groups [ 12 , 17 – 19 , 22 – 24 ].…”

“…Patients with the AA genotype were more prone to have AMD by nearly 26-fold. The association remained strong after data adjustment with [12,[17][18][19][22][23][24].…”

Age-Related Macular Degeneration: Pathophysiology, Management, and Future Perspectives

“…This work represents progress toward personalized and precision medicine, although it has yet to be applied in clinical practice. No other study has yielded results of genetic determinants strongly associated with AMD risk [15,16]. Current data suggest that clinical characteristics, such as baseline best-corrected visual acuity (BCVA) and neovascularization lesion size, are superior to genetic findings for predicting AMD progression and making treatment decisions [11,17].…”

“…Certain polymorphisms in ARMS2 and HTRA1 also are considered to confer risk of AMD [22]. Compared with control patients awaiting cataract surgery, patients with nAMD were significantly more likely to have certain polymorphisms in CFH (CC genotype), ARMS2 (TT), HTRA1 (AA), and C3 (CG), and these associations were stronger among women than among men [16]. Other investigators found that fewer than half of CFH variants were associated with AMD visual outcomes on anti-VEGF agents [19].…”

Associations of ARMS2 and CFH Gene Polymorphisms with Neovascular Age-Related Macular Degeneration

“…[13][14][15]41 In contrast to ARMS2, associations between CFH Y402H gene variants and nAMD have been less consistent. 42 For example, CFH Y402H in Caucasian had a strong association with nAMD, 4,14,43,44 but studies from Asian showed a conflicting result. Xu et al, 34 Gotoh et al, 45 Okamoto et al, 46 Uka et al, 47 and Chen et al 48 showed a weak association of CFH Y402H with AMD while Lau et al 49 showed a contradictory result.…”