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Related Experiment Videos

Modulating influence on HIV/AIDS by interacting RANTES gene variants.

Ping An1, George W Nelson, Lihua Wang

  • 1Intramural Research Support Program, SAIC-Frederick, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.

Proceedings of the National Academy of Sciences of the United States of America
|July 13, 2002
PubMed
Summary

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Certain genetic variations in the RANTES gene, particularly the In1.1C single nucleotide polymorphism (SNP), are linked to increased HIV-1 infection risk and faster AIDS progression. This RANTES SNP down-regulates gene transcription, potentially accelerating HIV-1 spread.

Area of Science:

  • Immunogenetics
  • Virology
  • Human Genetics

Background:

  • RANTES (regulated on activation normal T cell expressed and secreted) is a chemokine that inhibits HIV-1 replication in vitro.
  • Single nucleotide polymorphisms (SNPs) in immune-related genes can influence susceptibility and progression of infectious diseases.
  • Understanding genetic factors in HIV-1 infection is crucial for developing targeted interventions.

Purpose of the Study:

  • To investigate the association of RANTES gene single nucleotide polymorphism (SNP) variants and haplotypes with HIV-1 infection and AIDS progression.
  • To determine the functional impact of identified RANTES SNPs on gene transcription and their clinical relevance in diverse cohorts.

Main Methods:

  • Analysis of four RANTES SNPs and their haplotypes across five AIDS cohorts.

Related Experiment Videos

  • Genotyping of RANTES SNPs (promoter 403A, intron In1.1C, 3' UTR 3'222C).
  • Assessment of allele binding to nuclear proteins and gene transcription levels for the In1.1C SNP.

    • Main Results:

    • Three RANTES SNPs (403A, In1.1C, 3'222C) were associated with an increased frequency of HIV-1 infection.
    • The In1.1C SNP allele, located in an intronic regulatory element, down-regulates RANTES gene transcription.
    • In1.1C allele and haplotypes containing it showed a strong dominant association with rapid AIDS progression in African-American and European-American cohorts.

    Conclusions:

    • The RANTES In1.1C SNP is a significant genetic determinant of accelerated AIDS progression, potentially by diminishing RANTES transcription and facilitating HIV-1 spread.
    • The In1.1C genotype accounts for a substantial portion of attributable risk for rapid progression in African Americans and may be important in African populations.
    • RANTES genetic variants, particularly the down-regulating In1.1C allele, play a critical role in modulating HIV-1 infection susceptibility and AIDS progression rates.