Exploratory Study on Genetic Variants Related to Hydatidosis Susceptibility and Albendazole Pharmacogenetics in the Cusco Region in Peru

BACKGROUND: Hydatidosis, caused by Echinococcus granulosus, is a neglected zoonotic disease with significant public health implications in endemic regions, such as in Cusco, Peru. Genetic factors influencing susceptibility to infection and responses to albendazole, the primary treatment, remain unclear. Thus, this study aimed to investigates genetic polymorphisms associated with hydatidosis susceptibility and albendazole metabolism in the Cusco region. METHODS: Hence, a cross-sectional study was conducted using 20 individuals from endemic areas. Peripheral blood samples were collected for genomic DNA extraction, followed by single-nucleotide polymorphism (SNP) genotyping using the Illumina Global Screening Array. Polymorphisms in genes related to immunity (interleukin 10 (IL10), interleukin 17A (IL17A), vitamin D receptor (VDR), interferon gamma (IFNG), forkhead box P3 (FOXP3), interleukin 4 (IL4), tumor necrosis factor (TNF), toll-like receptor 4 (TLR4), cytotoxic T-lymphocyte antigen 4 (CTLA4), mannose-binding lectin 2 (MBL2), interleukin 12B (IL12B), and transforming growth factor-beta 1 (TGFB1)) and drug metabolism genes (cytochrome P450 family 3 subfamily A member 4 (CYP3A4), cytochrome P450 family 2 subfamily B member 6 (CYP2B6), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), ATP-binding cassette subfamily B member 1 (ABCB1), solute carrier organic anion transporter family member 1B1 (SLCO1B1), and cytochrome P450 family 2 subfamily E member 1 (CYP2E1)) were analyzed. RESULTS: High-frequency alleles were identified in six SNPs associated with susceptibility to Echinococcus granulosus: IL10 rs1800896 (77.5%), IL17A rs2275913 (97.5%), IFNG rs2779249 (92.5%), FOXP3 rs11568821 (97.5%), TGFB1 rs1800469 (80.0%), and VDR rs2228570 (87.5%). Likewise, elevated allele frequencies were observed for two SNPs potentially involved in albendazole metabolism: CYP3A4 rs2740574 (87.5%) and CYP2B6 rs2266780 (97.5%). A comparative analysis with other populations revealed significant differences in SNP frequencies in the Cusco population, both in SNPs related to susceptibility (IL17A rs2275913, VDR rs2228570, and TGFB1 rs1800469; p < 0.001) and pharmacogenetic-related SNPs (CYP2B6 rs2266782, SLCO1B1 rs4149056, and CYP2E1 rs8330; p < 0.05), suggesting the existence of unique local genetic patterns. CONCLUSION: These findings underscore the importance of pharmacogenetic screening to optimize albendazole therapy and support precision medical approaches for hydatidosis management in endemic regions. Further studies with larger cohorts are required to confirm these associations.