DC-SIGN and DC-SIGNR genetic diversity among different ethnic populations: Potential implications for pathogen recognition and disease susceptibility

Dendritic cell–specific intracellular adhesion molecule-3–grabbing nonintegrin (DC-SIGN) and DC-SIGNR are C-type lectins that serve both as cell adhesion and pathogen recognition receptors. Because of the essential role of the these molecules in the immune response, the implication of their alleles in human disease states, and the possible genetic variation at these loci among ethnically diverse populations, we undertook a study to analyze the full extent of DC-SIGN and DC-SIGNR polymorphisms in Caucasian Canadian and indigenous African populations. We report several novel nucleotide variants within regulatory 5′- and 3′-untranslated regions of the genes that could affect their transcription and translation. There were significant differences in the distribution of DC-SIGN and DC-SIGNR alleles among African and non-African populations. Finally, our study clearly demonstrates that Africans show greater genetic diversity at these two closely-related immune loci than observed in other major population groups. The differences may reflect evolutionary pressures generated by environmental factors, such as prevalent pathogens in these geographically distinct regions. Further studies will be needed to determine the net impact of DC-SIGN and DC-SIGNR genetic variants on the expression, translation, and function of the proteins and to understand how these functional polymorphisms may affect immune responses or immune escape.