印度北部儿童川崎病与 ITPKC 基因多态性 rs28493229 和 rs2290692 的关联。
Association of ITPKC gene polymorphisms rs28493229 and rs2290692 in North Indian children with Kawasaki disease.
机构信息
Allergy Immunology Unit, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, 160012, India.
Gentic Metabolic Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, 160012, India.
出版信息
Pediatr Res. 2022 Oct;92(4):1090-1098. doi: 10.1038/s41390-021-01830-x. Epub 2021 Dec 24.
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.
背景
单核苷酸多态性（SNP）与川崎病（KD）的发病机制有关。在某些种族的儿童中观察到肌醇 1,4,5-三磷酸-3-激酶 C（ITPKC）基因的 SNP 与 KD 易感性和冠状动脉病变（CALs）有关，但在其他种族中没有。本研究旨在探讨印度北部队列的这种遗传关联。
方法
使用聚合酶链反应和限制性片段长度多态性研究了 50 名 KD 患儿和 50 名年龄和性别匹配的对照者的 ITPKC 基因的两个 SNP（rs28493229 和 rs2290692）。通过 Sanger 测序证实了研究结果。还对 SNP 的 GG 和 CC 基因型进行了荟萃分析。
结果
rs2290692 的 CG+GG 基因型与 KD 易感性显著相关（p=0.015，优势比=4.1，95%置信区间=1.38-13.83）。然而，ITPKC 基因的 SNP 的单等位基因或基因型与 KD 易感性均无显著相关性。荟萃分析也未显示这些 SNP 与 KD 易感性有任何显著关联。
结论
我们的研究结果表明，来自印度北部的儿童中，ITPKC 基因 SNP（rs28493229 和 rs2290692）与 KD 易感性无显著相关性。需要更大的多中心研究纳入不同的种族，以了解 KD 的遗传基础。
影响
虽然 ITPKC 基因的 SNP rs28493229 与 KD 的易感性无关，但 SNP rs2290692 的组合基因型与 KD 易感性相关。ITPKC 基因 SNP 对 KD 的影响在不同种族和民族之间是不同的。我们在印度人群中发现 rs2290692 组合基因型与 KD 之间存在关联。这项研究强调，KD 的表型和基因型关联因种族而异。需要更大的多中心研究来得出 KD 遗传关联的结论。
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