title: Analysis of CCR5 and SDF-1 genetic variants and HIV infection in Indian population.
abstract: HIV-1 infection and progression exhibits interindividual variation. The polymorphism in the chemokine receptors CCR5 and CXCR4, the principal coreceptors for HIV-1 and their ligands like SDF-1 have a profound effect in altering the HIV-1 disease progression rate. A single nucleotide polymorphism designated SDF1-3'UTR-801G-A has been associated with resistance to HIV-1 infection or delayed progression to AIDS. In this study, the SDF1-3'A polymorphism, CCR5∆32 polymorphism and CCR5 promoter polymorphism at positions 58934 G/T, 59029 G/A, 59353 T/C, 59356 C/T, 59402 A/G and 59653 C/T were analysed in Indian population. The polymorphisms in HIV-1 patients and healthy individuals were evaluated by conventional PCR, RFLP-PCR and direct sequencing techniques. The CCR5∆32 mutant allele was found to be almost absent in Indian population. The analysis of the CCR5-59356C/T polymorphism revealed a trend towards an association of the C allele with an increased risk of HIV-1 infection. The frequency of allele CCR5-59356C was higher in HIV-1 patients (100%) as compared to healthy control subjects (89%, P = 0.003). The correlation of SDF1-3'A and CCR5 promoter CCR5-58934G/T, CCR5-59029G/A, CCR5-59353T/C, CCR5-59402 A/G and CCR5-59653C/T polymorphisms and protection to HIV-1 infection and progression to AIDS was found to be nonsignificant. Nine haplotypes with more than 1% frequency were detected but were not significant in their protective role against HIV. Comparative analysis with global populations showed a noteworthy difference in CCR5 and SDF-1 polymorphisms' frequency distribution, indicating the ethnic variability of Indians. Although susceptibility to infections cannot be completely dependent on one or few genetic variants, it is important to remember that SDF-1 and CCR5 variants have been correlated globally with HIV-1 infection and disease progression. In the light of that, higher frequency of SDF-1 variants in the Indian population is noteworthy.
authors.affiliation: Department of Cell and Molecular Biology, B.V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Ahmedabad, Gujarat, India.
authors.forename: A
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Department of Cell and Molecular Biology, B.V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Ahmedabad, Gujarat, India.
authors.forename: Harish
authors.initials: H
authors.lastname: Padh
mesh_terms: D000328:Adult; D054377:Chemokine CXCL12 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000473:pathology; D015497:HIV-1 / Q000472:pathogenicity; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D019713:Receptors, CCR5 / Q000235:genetics*
chemical_list: C584933:CCR5 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019713:Receptors, CCR5