Rai_2025_Am.J.Hum.Biol_37_e70148

OBJECTIVES: The EPHX1 gene encodes human microsomal epoxide hydrolase 1, which helps in biotransformation processes. Its activity is influenced by combinations of genotypes at its polymorphic sites. There are no data on the EPHX1 gene variants in the Indian Himalayan and adjoining populations (HAAPs). Therefore, this study aims to investigate the activity-associated genotypes of the EPHX1 gene variants in the HAAPs. MATERIALS AND METHODS: The EPHX1 activity-associated variants, located in exon 3 (Tyr113His) and exon 4 (His139Arg), were analyzed among 607 samples from 16 different HAAPs. Genotype data from previously published 14 Indian populations were combined and evaluated for pan-India comparison. RESULTS: We observed the prevalence of low EPHX1 activity-associated genotypes compared to the intermediate and high activity combinations in the HAAPs. There was a significant difference (p < 0.05) between the HAAPs and the reference Indian population based on variants in the EPHX1 gene. Comparison based on linguistic affiliation revealed that low EPHX1 activity-related genotypes were significantly higher in frequency among Tibeto-Burman speaking HAAPs (p < 0.001), followed by the other three major linguistic groups in India. CONCLUSION: Our study highlights the variations in both the studied loci among the HAAPs. We observed the widespread presence of low-activity-associated genotypes of the EPHX1 gene in the HAAPs. The pan-India comparison revealed the highest prevalence of low-activity-associated genotypes among the Tibeto-Burman speaking HAAPs compared to other linguistic groups. In the future, high-resolution genetic and molecular studies on EPHX1 are necessary to corroborate this finding and better understand human health holistically.