Abstract
Background
Single-nucleotide polymorphisms (SNPs) of several genes are linked to the etiopathogenesis of Kawasaki disease (KD). Association of SNPs of inositol 1,4,5-triphosphate-3-kinase C (ITPKC) gene with susceptibility to KD and coronary artery lesions (CALs) has been observed in children of certain ethnicities, but not from others. The present study was planned to explore this genetic association in the North Indian cohort.
Methods
Fifty children with KD and 50 age- and sex-matched controls were studied for two SNPs (rs28493229 and rs2290692) of the ITPKC gene using polymerase chain reaction and restriction fragment length polymorphism. Findings were confirmed by Sanger sequencing. A meta-analysis was also carried out for GG and CC genotypes of the SNPs.
Results
There was significant association between KD susceptibility and CG + GG genotype of rs2290692 (p = 0.015, odds ratio = 4.1, 95% confidence interval = 1.38–13.83). None of the single alleles or genotypes of the SNPs of ITPKC were, however, significantly associated with KD susceptibility. A meta-analysis also did not show any significant association of these SNPs to KD susceptibility.
Conclusions
Our findings suggest that ITPKC gene SNPs (rs28493229 and rs2290692) did not have a significant association with susceptibility to KD in children from North India. Larger multicentric studies incorporating different ethnicities are required to understand the genetic basis of KD.
Impact
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While SNP rs28493229 of the ITPKC gene is not found to be associated with susceptibility to KD, the combined genotype of SNP rs2290692 is shown to be associated.
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Impact of ITPKC gene SNP on KD is different across different races and ethnicities. We could find an association of the combined genotype of rs2290692 with it in the Indian population.
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This study highlights that phenotype and genotypic association of KD varies with ethnicities. Larger multicentric studies are required to reach a conclusion regarding the genetic association of KD.
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Data availability
All data generated or analysed during this study are included in this published article (and its supplementary information file).
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Acknowledgements
We wish to thank Prof. Bhavneet Bharti for their help in statistical analysis.
Funding
The authors thankfully acknowledge the Indian Council of Medical Research, New Delhi, India for financial assistance—Thesis Grant No. 3/2/June-2017/PG-Thesis-HRD (50) dated 13 March 2018. The funding agency had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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D.B.: conception and design, acquisition of data, data analysis, data interpretation, drafting manuscript, editing, and critical revision. R.K.: acquisition of data and data analysis. A.K.: acquisition of data and data analysis. An.K.: concept and design of the study, data interpretation, editing of the draft, and critical revision. P.S.: data interpretation, editing draft, and critical revision. A.R.: design of the study, acquisition of data, and data analysis. S.S.: concept and design of the study, clinical data, editing, critical revision, and approval of the final version.
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Informed written consent is taken from parents of all subjects and controls. An assent was obtained from all children above 7 years of age. This study was approved by Institute Ethics Committee and Institute Thesis Committee and Departmental Review Board.
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Bhattarai, D., Kumrah, R., Kaur, A. et al. Association of ITPKC gene polymorphisms rs28493229 and rs2290692 in North Indian children with Kawasaki disease. Pediatr Res 92, 1090–1098 (2022). https://doi.org/10.1038/s41390-021-01830-x
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DOI: https://doi.org/10.1038/s41390-021-01830-x
