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Association of HERPUD1 genetic variant rs2217332 with age-related macular degeneration and polypoidal choroidal vasculopathy in an Indian cohort

  • Genetics
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Abstract

Purpose

Age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are sister diseases and have several similar clinical features and still have few genetic differences. The association of HERPUD1 (homocysteine inducible ER protein with ubiquitin like domain 1) gene variant rs2217332 with PCV is known; however, such association with AMD has not been reported in the Indian population. We analyzed the association of rs2217332 with PCV and AMD to identify the preferential association of this variant with these diseases.

Methods

This is a population-based case–control study consisting of 422 patients (129 AMD cases; 101 PCV cases, 192 healthy controls) recruited from the vitreoretinal clinic Sankara Nethralaya. The sample size for the study was calculated using appropriate power calculation methods. Genotype was determined using PCR-based Sanger sequencing. The SPSS V23.0 statistical package tool was used to calculate chi-square and ROC to determine the association of rs2217332 with control, AMD, and PCV.

Results

Here, we report for the first time the association of this genetic variant (rs2217332) with AMD and PCV in the Indian population. The case–control study shows a significant association of this SNP with PCV (P value = 0.002); however, this variant is not significantly associated with AMD (P value = 0.602). Comparison between AMD (as control) and PCV (as case) also showed significant association of the SNP with PCV (P value = 0.02). Minor allele A conferred to increase the risk of PCV.

Conclusions

The study concludes that the genetic variant rs2217332 in HERPUD1 gene is highly significantly associated with PCV and not with AMD in Indian populations.

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Funding

This work was supported by Bayer Zydus Pvt. Ltd, Bombay. Funding Reference Number: 35 (I) (II) 51 dated 13 November 2019.

Author information

Author notes

  1. Yazhini Ramaswamy

    Present address: Department of Biological Sciences, National University of Singapore, Singapore, 119077, Singapore

  2. Deepak Kumar Sundaramoorthy

    Present address: Department of Molecular and Cellular Biology, Ludwig-Maximilians-Universität München, Großhaderner Straße 2-4, 82152, Planegg-Martinsried, Germany

  3. Lakshmi Priyankka Alagappan and Yazhini Ramaswamy contributed equally to this work.

Authors and Affiliations

  1. SN ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Sankara Nethralaya campus, Chennai, 600006, India

    Lakshmi Priyankka Alagappan, Yazhini Ramaswamy, Deepak Kumar Sundaramoorthy, Joshitha Bhaskar, Sripriya Sarangapani & Sinnakaruppan Mathavan

  2. School of Chemical and Biotechnology, SASTRA University, Tanjore, 613401, India

    Lakshmi Priyankka Alagappan

  3. Shri Bhagwan Mahavir Department of Vitreo Retinal Services, Medical Research Foundation, Sankara Nethralaya, Chennai, 600006, India

    Parveen Sen, Rajiv Raman & Muna Bhende

Authors
  1. Lakshmi Priyankka Alagappan
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Contributions

LPA and YR shared most of the experiments, performed the data analysis, and drafted the manuscript. DKS and JB performed some of the experiments. RR, PKS, SS, and MB facilitated the patient recruitment and reviewed the manuscript. SM developed the conceptual ideas and designed the study, drafted the manuscript, and approved the final version of the manuscript.

Corresponding author

Correspondence to Sinnakaruppan Mathavan.

Ethics declarations

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Vision Research Foundation, Sankara Nethralaya Hospital Review Board (IRB Ethics Approval Number -Study code: 636–2017-P) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Name of the institute (IRB) that approved the study: Vision Research Foundation, Sankara Nethralya Hospital, Chennai.

Informed consent (consent for participation)

Human subjects (patients) were used for this study and patient recruitment was done in the vitreoretinal clinic of Sankara Nethralaya (Chennai-India) after obtaining informed consent from all the patients and controls to obtain 8 ml of blood sample.

Conflict of interest

The authors declare no competing interests.

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Significance

1. We are the first to report a comparative analysis of HERPUD1 (rs2217332) gene association with PCV, AMD, and controls in the Indian population.

2. The genetic variant rs2217332 shows a strong association with PCV but not with AMD.

3. This data support that AMD and PCV have significant genetic differences, even though they share some common clinical features.

Limitation

1. Small number of samples were validated in both diseases

2. Indian population is heterogeneous and hence a large sample size may be good.

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Alagappan, L.P., Ramaswamy, Y., Sundaramoorthy, D.K. et al. Association of HERPUD1 genetic variant rs2217332 with age-related macular degeneration and polypoidal choroidal vasculopathy in an Indian cohort. Graefes Arch Clin Exp Ophthalmol 261, 1205–1212 (2023). https://doi.org/10.1007/s00417-022-05861-w

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  • DOI: https://doi.org/10.1007/s00417-022-05861-w

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