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MCP-1-MCP-3-Eotaxin gene cluster influences HIV-1 transmission.
AIDS 2003; 17(16):2357-65AIDS

Abstract

BACKGROUND

MCP-1 (CCL2), MCP-3 (CCL7), and eotaxin (CCL11) are genes for CC chemokines clustered on the long arm of chromosome 17. Previous studies have implicated these chemokines in monocyte recruitment, viral replication, and anti-HIV cytotoxic T cell responses. An epidemiological analysis identified genetic variants influencing HIV-1 transmission and disease progression.

METHODS

Genomic DNA from over 3000 participants enrolled in five natural history cohorts in the United States were analyzed. Nine single nucleotide polymorphisms (SNP) covering 33 kb containing these three genes were genotyped using the polymerase chain reaction. Distortions in allele, genotype, and haplotype frequencies were assessed with respect to HIV-1 transmission and rates of disease progression using categorical and survival analyses.

RESULTS

Extensive linkage disequilibrium was observed. Three SNP (-2136T located in the MCP-1 promoter region, 767G in intron 1 of MCP-1, and -1385A in the Eotaxin promoter) were nearly always found together on a 31 kb haplotype (H7) containing the three genes. Frequencies of the three variants and the H7 haplotype were significantly elevated (odds ratio, 0.6; P = 0.005-0.01) in uninfected European-Americans repeatedly exposed to HIV-1 through high-risk sexual behavior or contaminated blood products.

CONCLUSIONS

Although the extensive linkage disequilibrium precludes positive identification of the causal variant, the results suggest that genetic variation in the H7 region influences susceptibility to HIV-1 infection. Since these chemokines do not bind the primary HIV-1 coreceptors CCR5 or CXCR4, the observed influence on transmission may result from activation of the immune system in response to infection rather than receptor blockage.

Authors+Show Affiliations

SAIC Frederick and the Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14571188

Citation

Modi, William S., et al. "MCP-1-MCP-3-Eotaxin Gene Cluster Influences HIV-1 Transmission." AIDS (London, England), vol. 17, no. 16, 2003, pp. 2357-65.
Modi WS, Goedert JJ, Strathdee S, et al. MCP-1-MCP-3-Eotaxin gene cluster influences HIV-1 transmission. AIDS. 2003;17(16):2357-65.
Modi, W. S., Goedert, J. J., Strathdee, S., Buchbinder, S., Detels, R., Donfield, S., ... Winkler, C. (2003). MCP-1-MCP-3-Eotaxin gene cluster influences HIV-1 transmission. AIDS (London, England), 17(16), pp. 2357-65.
Modi WS, et al. MCP-1-MCP-3-Eotaxin Gene Cluster Influences HIV-1 Transmission. AIDS. 2003 Nov 7;17(16):2357-65. PubMed PMID: 14571188.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MCP-1-MCP-3-Eotaxin gene cluster influences HIV-1 transmission. AU - Modi,William S, AU - Goedert,James J, AU - Strathdee,Steffanie, AU - Buchbinder,Susan, AU - Detels,Roger, AU - Donfield,Sharyne, AU - O'Brien,Stephen J, AU - Winkler,Cheryl, PY - 2003/10/23/pubmed PY - 2004/5/22/medline PY - 2003/10/23/entrez SP - 2357 EP - 65 JF - AIDS (London, England) JO - AIDS VL - 17 IS - 16 N2 - BACKGROUND: MCP-1 (CCL2), MCP-3 (CCL7), and eotaxin (CCL11) are genes for CC chemokines clustered on the long arm of chromosome 17. Previous studies have implicated these chemokines in monocyte recruitment, viral replication, and anti-HIV cytotoxic T cell responses. An epidemiological analysis identified genetic variants influencing HIV-1 transmission and disease progression. METHODS: Genomic DNA from over 3000 participants enrolled in five natural history cohorts in the United States were analyzed. Nine single nucleotide polymorphisms (SNP) covering 33 kb containing these three genes were genotyped using the polymerase chain reaction. Distortions in allele, genotype, and haplotype frequencies were assessed with respect to HIV-1 transmission and rates of disease progression using categorical and survival analyses. RESULTS: Extensive linkage disequilibrium was observed. Three SNP (-2136T located in the MCP-1 promoter region, 767G in intron 1 of MCP-1, and -1385A in the Eotaxin promoter) were nearly always found together on a 31 kb haplotype (H7) containing the three genes. Frequencies of the three variants and the H7 haplotype were significantly elevated (odds ratio, 0.6; P = 0.005-0.01) in uninfected European-Americans repeatedly exposed to HIV-1 through high-risk sexual behavior or contaminated blood products. CONCLUSIONS: Although the extensive linkage disequilibrium precludes positive identification of the causal variant, the results suggest that genetic variation in the H7 region influences susceptibility to HIV-1 infection. Since these chemokines do not bind the primary HIV-1 coreceptors CCR5 or CXCR4, the observed influence on transmission may result from activation of the immune system in response to infection rather than receptor blockage. SN - 0269-9370 UR - https://www.unboundmedicine.com/medline/citation/14571188/MCP_1_MCP_3_Eotaxin_gene_cluster_influences_HIV_1_transmission_ L2 - http://Insights.ovid.com/pubmed?pmid=14571188 DB - PRIME DP - Unbound Medicine ER -