Genomic polymorphism of CD209 gene is associated with sickle cell disease in African children (HUM2P.328)

Abstract Sickle cell disease (SCD) presents with multiple complications and marked variability in severity among individuals and possible underlying differences in ethnic-specific disease pathogenesis. The CD209 gene otherwise called DC-SIGN encodes a transmembrane receptor and is expressed on the surface of dendritic cells with multiple studies showing association between its variants and susceptibility to infections. In SCD, vaso-occlusive crises and infections are common occurrences, and the role of CD209 is currently unknown. We examined the genotypic and allelic diversity of CD209 gene and determined its association with SCD in African children. Genomic DNA from 145 children (HbSS) and 244 controls (HbAA) were analyzed for polymorphic variants of CD209 by PCR-RFLP. All SNPs follow Hardy-Weinberg equilibrium (P>0.05). There was a significant difference in both genotypic and allelic frequencies (P=0.004 and P=0.015 respectively) of a promoter variant in CD209, DC-SIGN1-336 between SCD and controls. Additionally, genotype GG variant is less frequent (10.3% versus 22.1%) and significantly associated with sickle cell disease (OR=0.3868; P=0.0010) and this reduced frequency reveals an impaired or reduced capacity to mount an immune response to infectious pathogens. The implications of this finding for delineating disease co-morbidity or as genetic modifiers of SCD pathophysiology, and its significance in African American children with SCD will be explored