AEGiS-14IAC: Novel CCR2 mutations and single-nucleotide polymorphisms (SNPs) identified in HIV infected Africans using a new comprehensive assay.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Novel CCR2 mutations and single-nucleotide polymorphisms (SNPs) identified in HIV infected Africans using a new comprehensive assay.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10063)

Petersen DC, Zeier MD, Laten A, Grimwood A, Vardas E, Janse van Rensburg E, Hayes VM
Department of Medical Virology, University of Stellenbosch, Tygerberg Medical School, Cape Town, South Africa

BACKGROUND: A single nucleotide polymorphism (SNP) at codon 64 in the CC chemokine receptor 2 gene (CCR2V64I), has been associated with a dominant effect of delaying disease progression from HIV-1 infection to AIDS. The aim of our study was to design a comprehensive mutation detection assay for the entire coding region of the CCR2A and CCR2B gene transcripts and to identify novel mutations and SNPs, within our predominantly African-based population, which could influence an individual's susceptibility to HIV-1 infection and/or progression to AIDS.

METHODS: A mutation detection assay, based on denaturing gradient gel electrophoresis (DGGE), was designed for the entire coding region of both the CCR2A and CCR2B transcripts, including all relevant splice site junctions. The assay allows for the complete analysis of 5 individuals per denaturing gel. We used the assay to analyse a study cohort consisting of 102 HIV seropositive patients and 144 HIV seronegative controls from the diverse South African population.

RESULTS: Application of the CCR2-DGGE assay resulted in the detection of two previously reported CCR2 polymorphisms, namely CCR2V64I and CCR2N260, and 11 novel mutations, including seven SNPs occurring at high allelic frequencies within specific population groups of South Africa.

CONCLUSION: The large number of novel mutations / SNPs identified, using the CCR2-DGGE assay, indicates the importance for comprehensive analysis of all candidate genes in host susceptibility to HIV-1 infection in the under-studied African-based populations. The novel CCR2 SNPs can be used for further HIV-1 disease association studies.

Keywords: AEGIS, HIV Infections, Polymorphism, Single Nucleotide, HIV Seropositivity, Mutation, HIV-1, African Continental Ancestry Group, Receptors, Chemokine, Acquired Immunodeficiency Syndrome, Polymorphism (Genetics), Disease Progression, Ethnic Groups, South Africa, monocyte chemoattractant protein 1 receptor, Human, genetics

020707
A10063