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

Nur Afiqah Mohamad,Fan Kee Hoo,Liyana Najwa Inche Mat,Yoke Mun Chan,Nor Fariza Ngah,Vasudevan Ramachandran,Wan Aliaa Wan Sulaiman,Hazlita Mohd Isa,Siew Mooi Ching,Mohd Hazmi Mohamed

doi:10.1186/s40246-019-0197-3

Nur Afiqah Mohamad, Fan Kee Hoo + Show 8 more

Open Access

https://doi.org/10.1186/s40246-019-0197-3

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Abstract

BackgroundThe 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.ResultsBoth 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).ConclusionsThe 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.

Highlights

The association of high-temperature requirement A serine peptidase 1 (HTRA1) rs11200638 and ARMS2 rs10490924 gene polymorphisms with response to intravitreal ranibizumab therapy among neovascular Age-related macular degeneration (AMD) subjects in Malaysia was determined in this study, followed by the expression of HTRA1 and ARMS2 genes
Rs11200638 polymorphism at the promoter region of HTRA1 was suggested to be related to overexpression of the gene among neovascular AMD (nAMD) patients with the minor A allele, which was related to a significantly lower expression of HTRA1 mRNA compared with the major G allele [9, 10]
We reported an association of complement factor H gene [24, 33], Vascular endothelial growth factor (VEGF) + 405 G/C [34] and complement factor 3 R102G [35] gene polymorphisms with AMD among Malaysians

Summary

Introduction

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. The ARMS2 and HTRA1 genes are located nearby on the 10q26 chromosome in a strong linkage disequilibrium which could be the main reason for these inconsistent results as most genetic association studies have insufficient data on distinguishing these two genes with nAMD. Rs11200638 polymorphism at the promoter region of HTRA1 was suggested to be related to overexpression of the gene among nAMD patients with the minor A allele, which was related to a significantly lower expression of HTRA1 mRNA compared with the major G allele [9, 10]. Wang et al showed that there are no significant changes to the HTRA1 rs11200638 and ARMS2 rs104909 24 mRNA levels among AMD [11]

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