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Screening of PCSK9 and LDLR genetic variants in Familial Hypercholesterolemia (FH) patients in India

Journal of Human Genetics volume 66, pages 983–993 (2021)Cite this article

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Abstract

Familial Hypercholesterolemia (FH) is an autosomal, dominant, inherited disorder characterized by severely elevated LDL-cholesterol (LDL-C) levels with high risk for Coronary Artery Disease (CAD). There are limited genetic studies especially on genes other than Low Density Lipoprotein receptor (LDLR) conducted in Indian population. Thus, our aim was to screen the entire Proprotein Convertase Subtilisin/Kexin type 9 gene (PCSK9) gene & hotspot exons 3, 4 and 9 of LDLR gene in FH cases and controls. 50 FH cases were categorized into definite, probable and possible cases according to Dutch Lipid Network Criteria (DLNC) who were gender matched with 50 healthy controls. All 12 exons of PCSK9, and hotspot exons 3, 4 & 9 of LDLR gene were screened through High Resolution Melt (HRM) curve analysis. Enzyme linked immunosorbent assay was performed to measure circulating PCSK9 levels. Total cholesterol and LDL-C were significantly high in all three groups of cases. Total 8 nonpathogenic variants in exon 1, 5, 7 and 9 of the PCSK9 gene were detected. In LDLR gene, 3 known pathogenic and 1 benign variant were found in exon 3 & 4. In FH cases, PCSK9 levels were significantly high compared to controls (P = 0.0001), and were directly correlated to LDL-C (P = 0.0001) and Total Cholesterol (P = 0.0001). Our study is first to screen the entire PCSK9 gene in western part of India. Since no pathogenic variants were identified, it is possible that PCSK9 variants are clinically less relevant. However, 3 known pathogenic variants were found in the LDLR gene. These findings support our understanding of the genetic spectrum of FH in India.

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Acknowledgements

National Health Education Society (NHES), P. D Hinduja Hospital and Medical Research Centre and European Atherosclerosis Society – Familial Hypercholesterolemia Studies Collaboration (EAS-FHSC).

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Authors and Affiliations

  1. Research Laboratories, P. D Hinduja Hospital & Medical Research Centre, Mumbai, India

    Lakshmi Lavanya Reddy

  2. Department of Laboratory Medicine, P. D Hinduja Hospital & Medical Research Centre, Mumbai, India

    Swarup A. V. Shah & Tester F. Ashavaid

  3. Department of Cardiology, P. D Hinduja Hospital & Medical Research Centre, Mumbai, India

    Chandrashekhar K. Ponde, Rajesh M. Rajani & Sudhir K. Pillai

  4. Department of Cardiology, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, India

    Jamshed J. Dalal

  5. Research Department, P. D Hinduja Hospital and Medical Research Centre, Mumbai, India

    Raj G. Jatale

  6. Department of General Medicine, P. D Hinduja Hospital & Medical Research Centre, Mumbai, India

    Reeta J. Dalal & Chander V. Vanjani

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  1. Lakshmi Lavanya Reddy
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Reddy, L.L., Shah, S.A.V., Ponde, C.K. et al. Screening of PCSK9 and LDLR genetic variants in Familial Hypercholesterolemia (FH) patients in India. J Hum Genet 66, 983–993 (2021). https://doi.org/10.1038/s10038-021-00924-y

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