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Angiogenesis related genes in Takayasu Arteritis (TAK): robust association with Tag SNPs of IL-18 and FGF-2 in a South Asian Cohort

Journal of Human Genetics volume 69, pages 13–18 (2024)Cite this article

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Abstract

We performed genetic association study for genes encoding angiogenic and angiostatic proteins in patients with Takayasu arteritis (TAK). A total of 96 SNPs involving 60 genes were studied. Genotyping was performed in Fluidigm 96.96 Dynamic Array chip. All statistical analysis for SNP evaluation was performed using PLINK software. Initial analyses revealed five SNPs from three genes [IL-18 (encodes Interleukin-18), FGF2 (encodes Fibroblast Growth Factor-2), and ANGPT1 (encodes Angiopoietin-1)] as significantly different between controls and cases (uncorrected p < 0.05). After permutation-based analysis, two tag SNPs on the promoter region of IL-18 (rs187238 and rs1946518) and one 3’UTR tag SNP (rs1476217) of FGF2 were significantly associated with susceptibility to TAK, with p and OR (95% CI) of 0.0006 and 1.64 (1.25–2.17), 0.03 and 1.28 (1.02–1.64) & 0.016 and 1.33 (1.05–1.67), respectively; while, the two tag SNPs of ANGPT1 gene (rs6469101 and rs16875900) showed a trend (p = 0.055 & p = 0.051, respectively after permutation based correction). There is robust linkage disequilibrium between the two tag SNPs of IL-18 gene as validated by 1000 genome data of South Asian population; the eQTL effects of these tag SNPs of IL-18 and FGF2 genes on adjacent genes further suggest that these tag SNPs act as genetic risks for development of TAK in South Asians, with possible functional implications towards future biomarker development. Genotype phenotype study by genetic model-based analysis also revealed associations between genotype subsets and clinical features like fever, visual loss, left subclavian and coronary artery involvement in our TAK patients.

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Acknowledgements

We thank Ms. Hindumathi Mohan and Babu Raman for collection, storage and processing of blood samples from recruited subjects. Dr. Dolly Daniel, Professor of Transfusion Medicine, Christian Medical College Hospital, Vellore, India for recruitment of healthy donors from Blood Bank.

Funding

This study was funded by the research grant from the Science and Engineering board, Department of Science and Technology to Debashish Danda (SB/SO/HS/170/2013).

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Author notes

  1. These authors contributed equally: Debashish Danda, Ruchika Goel, Jayakanthan Kabeerdoss.

Authors and Affiliations

  1. Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, Tamil Nadu, India

    Debashish Danda, Ruchika Goel, Jayakanthan Kabeerdoss & Anisea Lincy Franklin

  2. Department of Paediatrics, Post Graduate Institute of Medical Education & Research, Chandigarh, India

    Jayakanthan Kabeerdoss

  3. Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

    Celi Sun & Swapan K. Nath

  4. Department of Medical Genetics, Christian Medical College, Vellore, Tamil Nadu, India

    Sumita Danda

  5. Department of Cardiology, Christian Medical College, Vellore, Tamil Nadu, India

    George Joseph

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  1. Debashish Danda
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Contributions

DD for conceptualising the hypothesis, DD, JK, RG and SD were involved in planning and designing of study; DD, RG, JK, AF were involved in data collection and entry; DD, JK, JL, CS, RG, SKN were involved with statistical analysis of genotyping results; and DD, RG, JK, SD and SKN were involved with manuscript writing and critical analysis.

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Correspondence to Debashish Danda.

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Danda, D., Goel, R., Kabeerdoss, J. et al. Angiogenesis related genes in Takayasu Arteritis (TAK): robust association with Tag SNPs of IL-18 and FGF-2 in a South Asian Cohort. J Hum Genet 69, 13–18 (2024). https://doi.org/10.1038/s10038-023-01198-2

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