Sequence variants of chemokine receptor genes and susceptibility to HIV-1 infection |
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Authors: | M Parczewski M Leszczyszyn-Pynka M Kaczmarczyk G Adler A Bińczak-Kuleta B ?oniewska A Boroń-Kaczmarska A Ciechanowicz |
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Institution: | (1) Department of Cardiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226014, Uttar Pradesh, India;(2) Sahra Hospital, Lucknow, 226010, Uttar Pradesh, India;(3) Department of Biostatistics and Health Informatics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226014, Uttar Pradesh, India;(4) Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226014, Uttar Pradesh, India |
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Abstract: | Genetic susceptibility to HIV infection was previously proven to be influenced by some chemokine receptor polymorphisms clustering
on chromosome 3p21. Here the influence of 5 genetic variants was studied: Δ32CCR5, G(-2459)ACCR5, G190ACCR2, G744ACX3CR1 and C838TCX3CR1. They were screened in a cohort of 168 HIV-1 positive adults HIV(+) group] and 151 newborns control group] from northwestern
Poland. PCR-RFLP was performed to screen for the variants (except for A32CCR5 polymorphism, where PCR fragment size was sufficient to identify the alleles) and then electrophoresed on agarose gel to
determine fragment size. Distribution of genotypes and alleles was not significantly different between the groups except for
theCCR5 polymorphisms, with the A32 allele and the (-2459)ACCR5 allele more frequent among neonates than in the HIV(+) group. No Δ32/Δ32 homozygotes were found in the HIV(+) group, but
16.1% were Δ32/wt heterozygotes. In the control group, 1.3% were Δ32/Δ32 homozygotes and 26.0% were Δ32/wt heterozygotes.
Linkage between the chemokine polymorphisms was calculated using the most informative loci for haplotype reconstruction. Haplotypes
containing Δ32 CCR5,190GCCR2 and 744ACX3CR1 were found to be significantly more common in the control group. This suggests an association between these haplotypes and
resistance to HIV-1 infection. |
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