Sequence variants of chemokine receptor genes and susceptibility to HIV-1 infection

被引:0
作者
M. Parczewski
M. Leszczyszyn-Pynka
M. Kaczmarczyk
G. Adler
A. Bińczak-Kuleta
B. Łoniewska
A. Boroń-Kaczmarska
A. Ciechanowicz
机构
[1] Pomeranian Medical University,Department of Infectious Diseases and Hepatology
[2] Pomeranian Medical University,Department of Laboratory Diagnostics & Molecular Medicine
[3] Pomeranian Medical University,Department of Neonatology
来源
Journal of Applied Genetics | 2009年 / 50卷
关键词
chemokine polymorphism; haplotype; HIV infection susceptibility;
D O I
暂无
中图分类号
学科分类号
摘要
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.
引用
收藏
页码:159 / 166
页数:7
相关论文
共 181 条
  • [1] Alkhatib G(1996)CC-CKR: a RANTES, MIP1á, MIP1â receptor as a fusion cofactor for macrophage tropic HIV-1 Science 272 1955-1958
  • [2] Combardiere C(2004)Haplotype structure and linkage disequilibrium in chemokine and chemokine receptor genes Hum Genomics 1 255-273
  • [3] Broder CC(1998)Identification of CX J Biol Chem 273 23799-23804
  • [4] Feng Y(1996)CR1 Nature 382 667-673
  • [5] Kennedy PE(2004)HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5 J Med Genet 42 205-208
  • [6] Murphy PM(2000)Reappraisal of the historical selective pressures for the CCR5-Δ32 mutation Science 287 2274-2278
  • [7] Beger EA(2003)Rapid progression to AIDS in HIV[sup +] individuals with a structural variant of the chemokine receptor CX[sub 3]CR1 Proc Natl Acad Sci USA 100 15276-15279
  • [8] Clark VJ(2002)Evaluating plague and smallpox as historical selective pressures for the CCR5-D32 HIV-resistance allele Biochem J 368 753-760
  • [9] Dean M(2003)Cloning and functional characterization of the human fractalkine receptor promoter regions J Immunol 171 5305-5312
  • [10] Combardiere C(1997)Two novel fully functional isoforms of CX3CR1 are potent HIV coreceptors Lancet 349 922-923