Prevalence of mutation in CCR2 and SDF-1 genes in HIV-seronegative Thais

Abstract

In a series of important discoveries since 1995, chemokines and their receptorshave been shown to act as competitive inhibitors and co-receptors for HIV infectionrespectively. Recently, four polymorphisms in the genes encoding these molecules havebeen identified and correlated with a delayed HIV-1 disease progression rate, namely:CCR5(+,68)32, CCRSm303, CCR2-64I, and SDF1-3'A. Several reports have shown that theCCR5(+,68)532 allelic form is virtually absent among African and Asian populations.CCR2-64I allele is found in all racial groups tested at the frequency of 10% to 26%.For the SDFl-3'A allele frequency ranges widely across ethnic groups from 3-71%.Thais are distinct ethnically and geographically from previously studied cohorts, andthey comprise a distinct population in South East Asia. In addition, this populationis experiencing an HIV- 1 epidemic, spreading largely through heterosexual contact.However, previous studies of the allele frequency of CCR2-64I and SDF1-3'A have notcontained Thai subjects. This study was undertaken to determine the frequency of thepolymorphism alleles of these 2 genes in the healthy HIV-seronegative Thaipopulation. Blood samples were randomly collected from 200 blood donors, who were anti-HIVnegative, at the Thai Red Cross, National Blood Centre. Genomic DNA was extractedfrom whole blood. Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) assays were used to analyze the CCR2-64I and SDF1-3'A geneticpolymorphisms. In brief, the genomic DNA was amplified by using the specific primersfor CCR2 and SDF- 1. PCR products were then purified, followed by digestion withspecific restriction enzymes. The products were visualized in an agarose gel andclassified as wild type, heterozygous or homozygous for the mutation by the digestionpattern. Among the 200 subjects examined, four homozygous and 55 heterozygous for theCCR2-64I allele were observed; and 27 homozygous and 79 heterozygous for SDF1-3'Awere detected. The calculated allele frequencies were 0.1575 and 0.3325,respectively. The distributions of these two genotypes were in agreement withHardy-Weinberg equilibrium. This is the first genetic survey that has undertaken toexamine the frequency of the CCR2-64I and SDF1-3'A alleles in the Thai population.Our results document that the frequencies of these alleles in Thai population are notsignificantly different from those in other South East Asian populations and indicatethat these alleles are likely to be having an impact on the natural history of HIV-1infection in Thailand. Approximately 13.5 % of Thais showed SDF1-3'A homozygousmutation of which has shown associated with a marked slowing in disease progressionif one was HIV infection.