Department of Epidemiology and Biostatistics, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Baoan District Center for Disease Control and Prevention, Shenzhen, China.
Int J Infect Dis. 2020 Sep;98:268-274. doi: 10.1016/j.ijid.2020.06.104. Epub 2020 Jul 4.
Little is known about the association between genetic susceptibility and the severity of hand, foot, and mouth disease (HFMD) infected with coxsackievirus A6 (CV-A6).
Three hundred and sixty-four CV-A6 HFMD patients were enrolled, including 115 severe and 249 mild patients. A genome-wide association study (GWAS) was performed involving eight DNA pools of 115 severe and 115 mild CV-A6 HFMD patients pair-matched by age and gender. Differences in relative allele signal scores of SNPs in Illumina Human OmniZhongHua-8 BeadChips were compared between the two groups. The tag SNPS for potentially functional SNPs or their high linked SNPs were selected for individual genotyping in all 364 patients and assessed for their associations with severe CV-A6 HFMD using multivariable logistic regression analyses.
The top 30 significant SNPs obtained from pooled DNA GWAS analysis were checked for biological functions and their high linkage disequilibrium (LD) SNPs. Four tag SNPs (rs1558206, rs6927647, rs9375728 and rs10879355) were selected for further individual genotyping in 364 CV-A6 patients. Only SNP rs10879355 was associated with severe CV-A6 HFMD, with CC genotype having a greater risk of severe illness than TT+TC genotypes (OR=2.48, 95%CI: 1.34, 4.56). SNP rs4290270 is in complete LD with rs10879355 in Chinese Han children.
This is the first report that one potentially functional SNP rs4290270 in the TPH2 gene may be associated with the risk of severe CV-A6 HFMD.
关于遗传易感性与柯萨奇病毒 A6（CV-A6）感染所致手足口病（HFMD）严重程度之间的关系知之甚少。
纳入 364 例 CV-A6 手足口病患者，包括 115 例重症和 249 例轻症患者。对 115 例重症和 115 例轻症 CV-A6 手足口病患者按年龄和性别配对的 8 个 DNA 池进行全基因组关联研究（GWAS）。比较两组间 Illumina Human OmniZhongHua-8 BeadChips 中 SNP 的相对等位基因信号评分差异。对所有 364 例患者进行潜在功能 SNP 或其高连锁 SNP 的标签 SNP 个体基因分型，并采用多变量 logistic 回归分析评估其与重症 CV-A6 手足口病的相关性。
对 pooled DNA GWAS 分析获得的前 30 个显著 SNP 进行了生物学功能检查及其高连锁不平衡（LD）SNP 检查。选择了 4 个标签 SNP（rs1558206、rs6927647、rs9375728 和 rs10879355）在 364 例 CV-A6 患者中进一步进行个体基因分型。只有 SNP rs10879355 与重症 CV-A6 手足口病相关，CC 基因型比 TT+TC 基因型发生重症疾病的风险更高（OR=2.48，95%CI：1.34，4.56）。SNP rs4290270 与中国汉族儿童的 rs10879355 完全连锁。
这是首次报道 TPH2 基因中的一个潜在功能 SNP rs4290270 可能与重症 CV-A6 手足口病的发病风险相关。
