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

Abstract

This study aimed to determine the association of ARMS2 A69S, ARMS2 del443ins54, and CFH Y402H polymorphisms with neovascular age-related macular degeneration (nAMD) for the first time in an Indonesian population. Patients and Methods: Our case-control study involved 104 nAMD and 100 control subjects. AMD diagnosis was evaluated by retinal specialists based on color fundus photography and optical coherence tomography. The polymorphisms on CFH Y402H and ARMS2 A69S were analyzed by PCR-restriction fragment length polymorphism (PCR-RFLP), whereas ARMS2 del443ins54 was evaluated by PCR-based assay. Results: Significant allelic associations with nAMD were detected on all polymorphisms (P<0.05), with stronger association with the ARMS2 A69S (OR 3.13; 95% CI 2.08-4.71; P<0.001) and ARMS2 del443ins54 (OR 3.28; 95% CI 2.17-4.95; P<0.001) polymorphisms than with CFH Y402H (OR 2.08; 95% CI 1.08-3.99; P=0.028). Genotype analysis showed a statistical difference between nAMD and the control group for all polymorphisms (P<0.05). However, the association with nAMD was weaker for CFH Y402H (P=0.043) than for ARMS2 A69S and ARMS2 del443ins54 (P<0.001). A significant interaction between ARMS2 A69S and hypertension was documented (OR 9.53; 95% CI 3.61-25.1; P<0.001). Conclusion: Our findings indicate that ARMS2 A69S and ARMS2 del443ins54 polymorphisms are strongly associated with the risk of nAMD for the first time in an Indonesian population. The risk of nAMD increased when the presence of risk alleles from ARMS2 A69S was combined with the presence of hypertension.

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

“…This study adhered to the ethical standards of the Declaration of Helsinki of 1964 and its later amendments. The inclusion/exclusion criteria and the criteria for AMD diagnosis were as reported previously [ 3 ].…”

“…The procedures followed for extraction of the genomic DNA and gene amplification were as described previously [ 3 ]. The primer sequences were: forward 5′-TTCCCATCTGAGACCGCT-3′ and reverse 5′-GGAAAGTTCCTGCAAATCG-3′ [ 17 ].…”

“…Replication studies on different ethnic populations show consistent results [7][8][9][10][11][12][13][14][15][16][17][18][19][20], but there are no reports on Indonesian populations. In addition to CFH and ARMS2 [3], no other genetics factors have been examined in Indonesia. The aim of this study was to investigate the associations of HtrA1 with nAMD in the Indonesian population, of which the majority ethnic group is the Asian Malay group.…”

“…The three most strongly associated loci identified to date are located on chromosome one (1q31), CFH (rs1061170), chromosome 10 (10q26), ARMS2 (rs10490924; del443ins54), and HtrA1 (rs11200638) [ 2 ]. In an earlier study, we have shown that the ARMS2 rs10490924 and del443ins54 variants show a strong association with nAMD in Indonesia [ 3 ]. The position of the rs11200638 polymorphism in the genome is very close to those of the rs10490924 and del443ins54 polymorphisms [ 4 – 7 ].…”

The Circulating Level of IL-1β in Patients with Age-related Macular Degeneration (AMD) in Yogyakarta: Characteristics to Disease Activity

“…Study on Indonesian population with Neovascular AMD show high association to genetics [3] and lifestyle [4]. ARMS2 and CFH increase susceptibility to AMD while hypertension and smoking status is risk factors.…”