Ethnic Variation in G6PD Deficiency: Epidemiology and Mutation Spectrum in Southern China's Multiethnic Hub, Nanning

Glucose-6-phosphate dehydrogenase (G6PD) deficiency exhibits high prevalence in malaria-endemic regions and areas along the historic Maritime Silk Road. This study investigated the burden and genetic architecture of G6PD deficiency in Nanning, the ethnically diverse capital of Guangxi in southern China, where Southeast Asian gene flow has shaped population genetics. We screened 14 403 individuals for G6PD activity at The First Affiliated Hospital of Guangxi Medical University, defining deficiency as activity < 60% of adjusted male median (AMM = 2045 U/L). Among 2513 deficient cases (prevalence: 17.45%), frequency was significantly higher in males (63.75%) vs. females (36.25%; p < 0.001) and Han Chinese (60.92%) vs. Zhuang (39.08%; p = 0.925). Multiplex melting curve analysis (MMCA) of 2513 enzyme-deficient samples identified pathogenic mutations in 1161 cases, revealing 13 distinct variants. The predominant mutations were: c.1388G>A (39.53%; 459/1161), c.1376G>T (24.81%; 288/1161), and c.95A>G (12.40%; 144/1161). Mutation c.871G>A exhibited male bias (p < 0.001), while c.95A>G was Zhuang-enriched (p < 0.001). Sanger sequencing of MMCA-negative cases identified two rare pathogenic variants (c.406C>T, c.196T>A). Our findings establish Nanning as a region of exceptionally high G6PD deficiency prevalence and delineate a distinct mutation profile with sex- and ethnicity-linked distributions. These results provide critical insights for designing precision screening programs and public health strategies tailored to this genetically diverse population.