Complement-related gene polymorphisms and severity of Coxsackievirus A6-induced hand, foot, and mouth disease in chinese han children: a candidate-gene association study

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Background Severe hand, foot, and mouth disease (HFMD) poses a substantial threat to pediatric health. Host genetic factors, particularly those involved in complement activation, influence susceptibility to HFMD; however, the contribution of complement gene polymorphisms to disease severity remains unclear. Methods A total of 189 HFMD patients caused by coxsackievirus A6 (CVA6) were enrolled from Henan Children’s Hospital; among them, 94 were classified as severe cases and 95 as mild cases. Genomic DNA was isolated from peripheral blood leukocytes using a modified phenol–chloroform extraction protocol. PCR-RFLP was used for genotyping. Logistic regression assessed SNP associations with severe HFMD risk. Results Significant associations were observed for the following genetic variants between patients with mild and severe disease: Complement 5 (C5) rs3761847 (GA vs. GG: OR = 2.547, 95% CI: 1.084–5.982); C3 rs2250656 (TC vs. TT: OR = 1.850, 95% CI: 1.021–3.351); and complement factor H (CFH) rs1065489 (TT vs. GG: OR = 2.804, 95% CI: 1.164–6.751; GT vs. GG: OR = 2.337, 95% CI: 1.085–5.033). ROC analysis showed that complement-related gene polymorphisms had clinical utility for predicting HFMD severity (AUC = 0.653, 95% CI: 0.575–0.730). Moreover, specific genotypes were associated with changes in laboratory parameters. Conclusion Our results suggest that C5, C3, and CFH variants influence susceptibility to severe CVA6-induced HFMD in Chinese Han children. Complement gene polymorphisms may help clinicians identify children at higher risk.