Promoter polymorphisms in the JK*01 W.06 allele associated with the Jk(a + w) weak antigen phenotype

Abstract

Abstract Background The Kidd blood group system is critical in transfusion medicine, especially for delayed hemolytic reactions. However, the genetic background and molecular mechanisms underlying the weak antigen phenotype remain unclear. This study aimed to elucidate how the JK*01 W.06 allelic variant and its promoter region polymorphisms contribute to reduced Jka antigen expression in the weak antigen phenotype. Methods Serological techniques and flow cytometry identified 20 Jk(a + w) samples from 800 Han Chinese blood donors. Third-generation sequencing analyzed the JK gene haplotype sequences, quantifying the frequency of the JK*01 W.06 allele and characterizing promoter sequence variations. Dual-luciferase assays assessed the differential transcriptional activities of two distinct promoter sequences, Promoter-A and Promoter-B. Results In Jk(a + w) samples, the frequency of the JK*01 W.06 allele reached 62.5%, significantly higher than that in random samples (34.7%). Analysis of the promoter region sequences revealed that 76.00% of Jk(a + w) samples displayed the Promoter-B polymorphism, whereas Promoter-A was predominant in Jk(a+) samples (76.09%). The dual-luciferase assay demonstrated that Promoter-A exhibited higher transcriptional activity compared to Promoter-B. Conclusions This study uncovers the association between the JK*01 W.06 allelic variant and the Jk(a + w) phenotype, highlighting the pivotal role of promoter polymorphisms in potentially influencing the formation of the Jk(a + w) antigen through modulation of transcriptional activity.

Keywords

• Weak antigen
• Allele
• Promoter
• Polymorphisms