Association of HTRA1 and ARMS2 gene polymorphisms with response to intravitreal ranibizumab among neovascular age-related macular degenerative subjects

Abstract

Background The association of HTRA1 rs11200638 and ARMS2 rs10490924 gene polymorphisms with response to intravitreal ranibizumab therapy among neovascular AMD (nAMD) subjects in Malaysia was determined in this study, followed by the expression of HTRA1 and ARMS2 genes. Results Both single nucleotide polymorphisms (SNPs) recorded a significant association between nAMD and controls with HTRA1 rs11200638 at P = 0.018 (OR = 1.52, 95% CI = 1.07–215) and ARMS2 rs10490924 at P < 0.001 (OR = 2.44, 95% CI = 1.75–3.42). An association was also observed in response to ranibizumab for both SNPs in a logistic regression analysis ( P < 0.001). The mRNA levels in the HTRA1 variant between responder and non-responder groups were significantly different for the homozygous non-risk GG genotype ( P = 0.032). Conclusions The HTRA1 rs11200638 and ARMS2 rs10490924 gene polymorphisms are associated with nAMD among Malaysians. Both gene polymorphisms were also correlated with response to intravitreal ranibizumab therapy based on visual and anatomical outcomes especially the HTRA1 rs11200638 variant.

High-temperature requirement factor A1 rs11200638 polymorphism and age-related macular degenerative from a comprehensive analysis about 15316 subjects

“…The ARMS2 and HTRA1 genes are located nearby on the 10q26 chromosome in a strong linkage disequilibrium. Significant association was observed that ARMS2 rs10490924 was related response to ranibizumab treatment among wet AMD subjects [71]. CFH gene T1277C polymorphism is strong associated with both wet and dry AMD and may be contribute to the inflammation in the pathogenesis of AMD [79].…”

“…The full texts were then evaluated, and 49 additional articles were excluded due to duplication (7), meta-analysis or systematic analysis (26), clinical trial (10), randomized controlled trial (6). Finally, 35 different articles [26,[68][69][70][71][72] were included in our metaanalysis, including 38 case-control studies about HTRA1 gene rs11200638 polymorphism and AMD risk ( Table 1) and 27 case-control studies about HTRA1 gene rs11200638 polymorphism and wet or dry AMD risk ( Table 2). Five case-control studies [68][69][70][71][72] were not consistent with HWE in control groups.…”

“…Finally, 35 different articles [26,[68][69][70][71][72] were included in our metaanalysis, including 38 case-control studies about HTRA1 gene rs11200638 polymorphism and AMD risk ( Table 1) and 27 case-control studies about HTRA1 gene rs11200638 polymorphism and wet or dry AMD risk ( Table 2). Five case-control studies [68][69][70][71][72] were not consistent with HWE in control groups. To make our analysis to more strict, we deleted above five studies, so there were about 33 case-control studies (8101 cases and 7215 controls) for the whole AMD [26,, and 22 case-control studies for wet or dry (3938 cases and 4427 controls) studies [26, 30, 31, 33, 34, 40, 41, 43, 44, 46-48, 51, 53-56].…”

High-temperature requirement factor A1 rs11200638 polymorphism and age-related macular degenerative from a comprehensive analysis about 15316 subjects

“…Finally, 35 different articles [26, 30-57, 65-69] were included in our meta-analysis, including 38 case-control studies about HTRA1 gene rs11200638 polymorphism and AMD risk ( Table 1) and 27 case-control studies about HTRA1 gene rs11200638 polymorphism and wet or dry AMD risk ( Table 2). Five case-control studies [65][66][67][68][69] were not consistent with HWE in control groups. To make our analysis to more strict, we deleted above five studies, so there were about 33 case-control studies (8101 cases and 7215 controls) for the whole AMD [26, 30-57], and 22 case-control studies for wet or dry (3938 cases and 4427 controls) studies [26, 30, 31, 33, 34, 40, 41, 43, 44, 46-48, 51, 53-56].…”

“…The ARMS2 and HTRA1 genes are located nearby on the 10q26 chromosome in a strong linkage disequilibrium. Significant association was observed that ARMS2 rs10490924 was related response to ranibizumab treatment among wet AMD subjects [68]. CFH gene T1277C polymorphism is strong associated with both wet and dry AMD and may be contribute to the inflammation in the pathogenesis of AMD [76].…”