CD177 gene polymorphisms governing the differential expression of HNA-2 on neutrophils in Indians

Background CD177gp, also known as human neutrophil antigen (HNA)-2, is encoded by the CD177 gene located on chromosome 19. Different molecular mechanisms involving polymorphisms in the gene, mRNA splicing defects, DNA methylation, and so on govern the expression of HNA-2 on neutrophils ranging from 0% to 100%, with the unique biphenotypic expression observed in the majority of individuals. Its genotyping is often complicated by the presence of the pseudogene, CD177P1 . Methods In the present study, the CD177gp expression on the neutrophils of 102 individuals from Mumbai, India, was compared via flow cytometry using two clones, namely MEM-166 and TAG4. For genotyping of the CD177 gene, long-range PCR was employed. Phenotypic expression was then correlated with the CD177 gene polymorphisms to determine the molecular basis of HNA-2 in Indians. Results Overall, the median CD177 expression using the MEM-166 clone was 60.4% (Q1–Q3: 48.5–70.8), and using the TAG4 clone, it was 58.4% (Q1–Q3: 45.9–72.9). A statistically significant difference of 1.56% clone-dependent variation in expression was observed between the two clones (p = 0.007). On molecular genotyping, 17 different genotype patterns and 8 novel mutations were identified. The multi-locus genotype pattern containing NM_020406.4:c.787A>T was found in a heterozygous state in 8.8% of the samples, of which 66.67% of the samples had low expression of CD177gp. Conclusion This is the first study reporting the molecular characterization of the CD177 gene in individuals from Mumbai, India.