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Identifying the genetic associations among the psoriasis patients in eastern India

Journal of Human Genetics volume 69, pages 205–213 (2024)Cite this article

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Abstract

Psoriasis is a multifactorial genetic disorder manifested by hyperproliferation and abnormal differentiation of epidermal keratinocytes, along with the infiltration of inflammatory cells into the skin. Although ~80 genetic susceptibility variants were reported in psoriasis, many loci showed population-specific associations, warranting the need for more population-specific association studies in psoriasis. We determined the association of forty single nucleotide polymorphisms (SNPs) among 2136 psoriasis patients and normal individuals from eastern India. We investigated the expression of corresponding genes and evaluated the protein structure stability for the genes with susceptible coding variants. We found fifteen SNPs significantly associated with psoriasis, while additional three SNPs showed significant association when we classified the patients based on the presence of HLA-Cw6 allele. Epistatic interaction between HLA-Cw6 and other associated loci showed significant association with the SNPs at PSORS1 region, along with other five SNPs outside PSORS1. Three genes showed significant differential expression in psoriatic tissues compared to the adjacent normal skin tissues but were not differential when classified the patients based on their genotypes. SNP rs495337 at SPATA2 (Spermatogenesis Associated 2) showed a 1.2-fold increased risk among the HLA-Cw6 patients compared to combined samples. We found significant downregulation of SPATA2 among the patients with risk genotypes and HLA-Cw6 allele compared to the non-risk genotypes. Protein structure stability analysis showed reduced structural stability for all the mutant residues caused by the associated coding variants. Our study evaluated the genetic associations of psoriasis-susceptible variants in India and evaluated the possible functional significance of these associated variants in psoriasis.

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Acknowledgements

This work was supported by the Science and Engineering Research Board, Department of Science & Technology, Government of India (CRG/2020/003837), DBT, Govt. of West Bengal, India (572(sanc)/BT-RD-09/2015), and intramural research funding of the Indian Statistical Institute, India. The authors acknowledge all volunteers who participated in the study. SD was supported by the SERB Senior Research Fellowship under the SERB grant CRG/2020/003837. We thank Taniya Sarkar for her assistance in the genotyping work.

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Authors and Affiliations

  1. Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, West Bengal, 700108, India

    Shantanab Das, Aditi Chandra, Anamika Das & Raghunath Chatterjee

  2. Consultant Dermatologist, Uttarpara, Hooghly, West Bengal, 712258, India

    Swapan Senapati

  3. Department of Dermatology, IPGMER/SSKM Hospital, Kolkata, West Bengal, India

    Gobinda Chatterjee

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  1. Shantanab Das
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Contributions

RC and SD conceptualized the study, SD, AC and AD conducted the experiments, SS and GC recruited patients, SD analyzed the data and drafted the manuscript, RC, SS, GC, AC and AD edited and finalized the manuscript.

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Correspondence to Raghunath Chatterjee.

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The study was approved by the Institutional Ethics Committee for Human Research, Indian Statistical Institute, Kolkata, India and IPGMER/SSKM Hospital Kolkata.

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Das, S., Chandra, A., Das, A. et al. Identifying the genetic associations among the psoriasis patients in eastern India. J Hum Genet 69, 205–213 (2024). https://doi.org/10.1038/s10038-024-01227-8

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