Genetic Variants of NRAMP1 and Hepcidin ( HAMP ) in Cancer Patients Infected with Human Herpesvirus-6

Abstract

Human herpesvirus-6 (HHV-6) is involved in immune modulation and contributes to cancer development through interactions with host genetic factors. Hepcidin ( HAMP ) and NRAMP1 genes play essential roles in iron metabolism and innate immunity, yet their polymorphisms remain poorly investigated in HHV-6–associated cancers. This study investigated the association between HAMP and NRAMP1 gene polymorphisms and HHV-6 infection in 40 confirmed HHV-6–positive cancer patients compared with 40 non-cancer, HHV-6–negative controls. Genomic DNA was extracted and verified by agarose gel electrophoresis. Hepcidin polymorphisms were analyzed using Tetra-ARMS PCR, while NRAMP1 (3′UTR) polymorphism was detected by PCR-RFLP. Cancer patients exhibited wild-type, mutant, and heterozygous hepcidin genotypes, whereas controls predominantly showed the wild-type genotype. Although allele frequency analysis revealed no statistically significant difference for the G and TG + alleles between groups ( p = 0.23), the hepcidin A allele (521 bp) was more frequent among cancer patients, suggesting a possible association with increased cancer susceptibility (odds ratio = 2.111). For NRAMP1, three genotypic patterns were identified (TG−/TG−, TG+/TG+, and TG−/TG+), and while no significant between-group difference was detected ( p = 0.23), the TG+ allele demonstrated a potential two-fold increased cancer risk among carriers. These findings suggest that specific allelic variants—particularly the hepcidin A allele and NRAMP1 TG+ allele—may contribute to cancer susceptibility in HHV-6–infected individuals, highlighting a possible genetic–viral interaction that influences immune and iron-regulatory pathways in cancer development.