Sequence variants of chemokine receptor genes and susceptibility to HIV-1 infection.
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: Delta32 CCR5, G(-2459)A CCR5, G190A CCR2, G744A CX3CR1 and C838T CX3CR1. 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 Delta32 CCR5 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 the CCR5 polymorphisms, with the Delta32 allele and the (-2459)A CCR5 allele more frequent among neonates than in the HIV(+) group. No Delta32/Delta32 homozygotes were found in the HIV(+) group, but 16.1 percent were Delta32/wt heterozygotes. In the control group, 1.3 percent; were Delta32/Delta32 homozygotes and 26.0percent were Delta32/wt heterozygotes. Linkage between the chemokine polymorphisms was calculated using the most informative loci for haplotype reconstruction. Haplotypes containing Delta32 CCR5, 190G CCR2 and 744A CX3CR1 were found to be significantly more common in the control group. This suggests an association between these haplotypes and resistance to HIV-1 infection.
Parczewski
M
M
Pomeranian Medical University, Department of Infectious Diseases and Hepatology, Arkonska 4, 71-455 Szczecin, Poland. mparczewski@yahoo.co.uk
Leszczyszyn-Pynka
M
M
Kaczmarczyk
M
M
Adler
G
G
Binczak-Kuleta
A
A
Loniewska
B
B
Boron-Kaczmarska
A
A
Ciechanowicz
A
A
D000328:Adult; D000368:Aged; D000073883:CX3C Chemokine Receptor 1; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015658:HIV Infections / Q000235:genetics*; D015497:HIV-1; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D054390:Receptors, CCR2 / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics*
C515334:CCR2 protein, human; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine