AB0003 SINGLE-NUCLEOTIDE POLYMORPHISMS (RS28493229 AND RS2290692) IN ITPKC GENE IN CHILDREN WITH KAWASAKI DISEASE
Authors: D. Bhattarai, R. Kumrah, A. Kaur, A. Kaur, A. Rawat, S. Singh
Journal: Annals of the Rheumatic Diseases (2020)

Background: Kawasaki disease (KD) is an acute medium vessel vasculitis manifesting with mucocutaneous lesions and cardiac complications especially coronary artery lesions (CALs). Inositol 1,4,5-triphosphate 3-kinase C (ITPKC ) gene polymorphisms are have been shown to be associated with susceptibility to KD and CAL. Objectives: This study was designed to investigate the association of single nucleotide polymorphisms (SNPs) of the ITPKC gene with KD and CAL in Indian children. Methods: Two SNPs of the ITPKC gene (rs28493229 and rs2290692) were studied in 50 cases of KD and 50 healthy controls. The Deoxyribonucleic acid (DNA) samples from test subjects and controls were analysed for the two polymorphisms by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The allele, genotype, and haplotype frequencies were compared in different groups. A meta-analysis was also performed for the CC and GG genotype of both SNPs of interest. Results: No significant differences were found in frequencies of C allele, CC genotype and C carriers of rs28493229 and rs2290692. Combined CG+GG genotype frequency of rs2290692 was found to be significantly associated with susceptibility of KD (95% Confidence interval (CI) = 1.38-13.83, p = 0.015). A meta-analysis did not show a significant association of SNP rs28493229 (Odds ratio = 1.46, CI = 0.96-2.23) and rs2290692 (OR = 1.07, 95% CI = 0.663-1.731) of ITPKC and susceptibility to KD. Conclusion: Combined CG+GG genotype of SNP rs2290692 at 3’ UTR of the ITPKC gene was found to be significantly associated with susceptibility to KD. Our study did not show a significant association of any allele or genotype with susceptibility to KD. The meta-analysis combining our study with previous studies on these 2 SNPs also failed to show a significant association of different genotypes and susceptibility of KD. Table: Table 1. Allele, genotype and carrier frequencies of single nucleotide polymorphisms of rs28493229 and rs2290692 Allele, genotype and carrier frequencies of SNP rs28493229 of ITPKC (n = 100)Allele/ Genotype KD patients (n = 50) n (%) Controls (n = 50) n (%) Odds ratio (95% C.I.) P value G allele 89 (89%) 92 (92%) - - C allele 11 (11%) 8 (8%) 1.42 (0.49-4.26) 0.468 GG genotype 39 (78%) 42 (84%) - - CG genotype 11 (22%) 8 (16%) 1.48 (0.54-4.19) 0.446 CC genotype 0 (0%) 0 (0%) - - Frequencies of allele and genotype of rs2290692 SNPs in KD patients and controls (n = 100) Allele/ Genotype KD patients (n = 50) n (%) Controls (n = 50) n (%) Odds ratio (95% CI) P value G allele 63 (63%) 56 (56%) - - C allele 37 (37%) 44 (44%) 0.747 (0.41-1.36) 0.313 GG genotype 19 (38%) 20 (40%) - - CG genotype 25 (50%) 16 (32%) 1.64 (0.68-4.04) 0.272 CC genotype 6 (12%) 14 (28%) 0.45 (0.14-1.37) 0.173 C.I. Confidence interval, KD- Kawasaki disease Figure: Figure 1. Forest plot for the association between (A) CC genotype of rs28493229 and risk of having KD (B) GG genotype of rs2290692 and risk of having KD (C) CC genotype of rs2290692 and risk of having KD References: [1]McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. 2017 Apr 25;135(17):e927–99. [2]Onouchi Y, Gunji T, Burns JC, Shimizu C, Newburger JW, Yashiro M, et al. ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms. Nat Genet. 2008 Jan;40(1):35–42. [3]Peng Q, Chen C, Zhang Y, He H, Wu Q, Liao J, et al. Single-nucleotide polymorphism rs2290692 in the 3’UTR of ITPKC associated with susceptibility to Kawasaki disease in a Han Chinese population. Pediatr Cardiol. 2012 Oct;33(7):1046–53. Disclosure of Interests: None declared