One of the major goals of the human genome project is to understand the relationships between the genome and various phenotypes of interest. Such phenotypes include normal metabolic pressures and behavioral states, in addition to disease conditions. A number of different diseases have been shown to have a genetic basis including cancer predisposition, inborn errors of metabolism, and susceptibility to infectious agents. One infectious disease of primary interest is the acquired immunodeficiency syndrome (AIDS). Within the past several years, it has been demonstrated that the human immunodeficiency virus-1 (HIV-1) uses several chemokine receptors for cell entry. It has also been shown that the chemokine ligands (RANTES, MIP1-alpha and MIP1- beta) for the major HIV co-receptor, CCR5, can inhibit the replication of non-syncytium-forming HIV-1. Subsequent studies have revealed that mutations in several chemokines and receptors may prevent infection and/or may delay the onset of adverse clinical conditions. However, since epidemiological analyses have also shown that the known mutations in these genes do not explain all disease-related effects, a deeper appreciation of these and additional host genes is necessary for a complete understanding of the pathobiology of HIV-1. Currently about 40 distinct human chemokine genes have been identified. In the present study polymerase chain reaction (PCR) primers have been designed to encompass coding regions, transcription factor binding sites, and 5? and 3? untranslated regions for about 20 of these genes. A series of single nucleotide polymorphisms (SNPs) have been developed using the single strand conformational polymorphism (SSCP) technique and nucleotide sequence analyses. Approximately 40 SNPs have been identified to date. PCR-RFLP and Taq-Man allelic discrimination methods are being used to genotype up to 3000 clinically characterized individuals from the MACS, HGDS, ALIVE , MHCS, and SFCC HIV disease cohorts in an effort to identify genes responsible for HIV infection and/or AIDS disease progression. Results are available for analyses between clinical phenotypes and genotypes from 18 SNPs. Polymorphisms in four genes, LAG1, IL4, RANTES and MCP1, reveal an association with a clinical phenotype. Genetic Epidemiology of AIDS and the Role of Chemokine Genes - AIDS, asthma, Chemokines, Cytokines, Epidemiology, Genetic Susceptibility, linkage disequilibrium, PCR, chemokine receptors, - Human Tissues, Fluids, Cells, etc.
| Modi, William S; O'Brien, Thomas R; Vlahov, David et al. (2003) Haplotype diversity in the interleukin-4 gene is not associated with HIV-1 transmission and AIDS progression. Immunogenetics 55:157-64 |
| Modi, William S; Goedert, James J; Strathdee, Steffanie et al. (2003) MCP-1-MCP-3-Eotaxin gene cluster influences HIV-1 transmission. AIDS 17:2357-65 |
