Genetic diversity of CD14, CD28, CTLA-4 and ICOS gene promoter polymorphism in African and American sickle cell disease

Abstract Variable immune response to external stimuli remains a major concern in sickle cell disease (SCD), with such responses predicted to be contributors to disease pathogenesis. Elucidating the diversity of host genes contributing to immune response would assist to clarify differing outcomes among and between disease groups. We hypothesize that there is a significant interethnic diversity in the CD14 (rs2569190), CD28 (rs35593994), CTLA-4 (rs5742909) and ICOS (rs4404254) gene polymorphisms among and between SCD groups. We genotyped single nucleotide polymorphisms of the 4 loci among African and African American SCD and control groups and between SCD groups. In all, 375 individuals from Mali (145 SCD and 230 controls) and 700 DNA samples from the United States (321 SCD and 379 controls) were subjected to a PCR-RFLP assay. We found no intraethnic difference in genotypic and allelic frequencies of the 4 loci among Africans and African Americans, potentially significant in disease association studies, including a similar observation for interethnic frequencies of CD28, CTLA-4 and ICOS genes, but not CD14. The CD14 (rs2569190) gene promoter demonstrated a significant difference (p