Dharmagat Bhattarai1, Rajni Kumrah1, Anit Kaur1, Anupriya Kaur2, Priyanka Srivastava2, Amit Rawat1, Surjit Singh3. 1. Allergy Immunology Unit, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, 160012, India. 2. Gentic Metabolic Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, 160012, India. 3. Allergy Immunology Unit, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, 160012, India. surjitsinghpgi@rediffmail.com.
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: 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. 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. 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.
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: 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. 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. 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.
Authors: Brian W McCrindle; Anne H Rowley; Jane W Newburger; Jane C Burns; Anne F Bolger; Michael Gewitz; Annette L Baker; Mary Anne Jackson; Masato Takahashi; Pinak B Shah; Tohru Kobayashi; Mei-Hwan Wu; Tsutomu T Saji; Elfriede Pahl Journal: Circulation Date: 2017-03-29 Impact factor: 29.690