Clinical features and whole-genome snp association study of chronic active Epstein-Barr virus infection in adults

BACKGROUND: Adult chronic active Epstein-Barr virus infection (CAEBV) is rare, often atypical, lacks effective therapy, and has poor prognosis. Its geographic and ethnic clustering in East Asians suggests host genetic susceptibility. We aimed to define adult CAEBV clinical features and identify susceptibility SNPs and implicated genes and pathways. METHODS: Forty-six chronic EBV-infected adults and 74 healthy controls were genotyped using Illumina SNP arrays. After PLINK quality control, genome-wide association analysis was performed. Functional annotation was explored by GO/KEGG enrichment. RESULTS: GWAS identified 14,185 SNPs with nominal significance (P < 0.05). Seven risk-associated SNPs (OR > 1) were highlighted, including rs1172402, rs5942250, rs7009326, JHU_X.91,664,955, rs12202343, rs516251, and rs10148866. Ten SNPs showed potential protective effects (OR < 1), including rs10142901, rs80019788, rs77220782, rs58233940, rs7297554, rs3116565, rs208510, rs62411077, rs12564297, and rs2192444. Enrichment analyses indicated that differential loci were mainly related to cell junction/membrane components and to processes such as cell adhesion and calcium ion transport, involving calcium signaling, TRP channel-mediated inflammatory regulation, and PI3K-Akt/MAPK pathways. Core genes included PTEN, EGFR, PTK2, ITGB1, and DVL1. CONCLUSION: Adult CAEBV shows distinct SNP patterns versus healthy controls. Candidate susceptibility loci converge on calcium/TRP, PI3K-Akt, and MAPK signaling, with PTEN, EGFR, PTK2, ITGB1, and DVL1 as key genes.