ABSTRACT
The CCR5-Delta32 genotype is known to influence HIV-1 transmission and disease. We genotyped 1301 US women of various races/ethnicities participating in the HIV Epidemiologic Research Study. None was homozygous for CCR5-Delta32. The distribution of heterozygotes was similar in HIV-1 infected and uninfected women. Thirty-seven (11.8%) white, 28 (3.7%) blacks/African Americans (AA), seven (3.3%) Hispanics/Latinas, and one (6.6%) other race/ethnicity were heterozygous. The frequency of heterozygotes differed among sites for all races combined (P = 0.001). More heterozygotes were found in AA women in Rhode Island (8.9%) than in the other sites (3.1%) (P = 0.02), while heterozygosity in white women was most common in Maryland (28.6%) (P = 0.025). These regional differences could be accounted for by racial admixture in AAs, but not in whites. Regional variations should be considered when studying host genetic factors and HIV-1 in US populations.
Subject(s)
Genetic Variation , HIV Infections/genetics , HIV Infections/immunology , Receptors, CCR5/genetics , Adolescent , Adult , Base Sequence , Black People/genetics , Case-Control Studies , DNA/genetics , Female , Genotype , HIV Infections/epidemiology , HIV-1 , Heterozygote , Hispanic or Latino/genetics , Humans , Middle Aged , United States/epidemiology , White People/geneticsABSTRACT
On exposure to a pathogen, a host may resist infection, become subclinically infected, or progress through several stages from mild to severe infection. Chronic sequelae may or may not occur. Host factors, particularly host genes, influence many of these stages. We have used a model of the continuum of pathogenesis of infectious diseases to consider the effect of host genes on five pathogens of significant public health burden: Mycobacterium tuberculosis, Plasmodium species, human immunodeficiency virus, hepatitis B virus, and Vibrio cholerae. The relationships between these infections and polymorphisms in human leukocyte antigen, cytokines, other immune response, or pathogen receptor genes are reviewed. We discuss gene-gene interactions and their effects in complex settings, such as coinfections with several pathogens. Priorities for prevention and control of these pathogens include vaccines and antimicrobial drugs. Research on how host genes can influence vaccine responses and the efficacy of drugs or other interventions, as well as further research into the relationship of host genes to infectious disease outcomes, may lead to new strategies for prevention and control.
