Association of DC-SIGN promoter polymorphism with increased risk for parenteral, but not mucosal, acquisition of human immunodeficiency virus type 1 infection

There is considerable debate about the fundamental mechanisms that underlie and restrict acquisition of human immunodeficiency virus type 1 (HIV-1) Infection. In LIGHT of recent studies demonstrating the ability of C type lectins to facilitate Infection with HIV-1, we explored the potential relationship between polymorphisms in the DC-SIGN promoter and risk for acquisition of HIV-1 according to route of Infection. Using samples obtained from 1,611 European-American participants at risk for parenteral (n = 713) or mucosal (n = 898) Infection, we identified single-nucleotide polymorphisms in the DC-SIGN promoter using single-strand conformation polymorphism. Individuals at risk for parenterally acquired Infection who had -336C were more susceptible to Infection than were persons with -336T (odds ratio = 1.87, P = 0.001). This association was not observed in those at risk for mucosally acquired Infection. A potential role for DC-SIGN specific to systemic acquisition and dissemination of Infection is suggested.