Effects of polymorphisms of chemokine receptors on neurodevelopment and the onset of encephalopathy in children with perinatal HIV-1 infection.
This study examined the effects of chemokine receptor polymorphisms on neurodevelopment and the onset of encephalopathy in children with perinatal HIV-1 infection. Infected children (N = 121) between the ages of I and 72 months were categorized into dichotomous groups (heterozygous or homozygous mutant vs. homozygous wild type) for each chemokine receptor 2 (CCR2) and chemokine receptor 5 (CCR5) allele. Neurodevelopmental measures included the Bayley Scales of Infant Development (BSID)for children age < or = 30 months and the McCarthy Scales of Children's Abilities (MSCA) for children aged > 30 months. A basic linear spline was used to model the mean value at each visit for the relevant test index, with determination of the slope between 4-12 months, 12-30 months, and 31-72 months of age. A mixed model analysis of variance was used to compare differences between slopes (AP) and intercepts (AX) according to the presence or absence of the specified CCR2 or CCR5 polymorphism. Survival analyses were used to compare the onset of encephalopathy by chemokine receptor allelic grouping. After adjusting for potential confounds, statistically significant differences emerged in CCR5-39353, 39356, and 39402. Although the protective effects appeared to be discrete and transient, children with mutant CCR5 genotypes exhibited better neurodevelopmental outcomes than children with the wild type alleles. Chemokine polymorphisms did not appear to impact the onset of encephalopathy. Although possibly a temporary effect, HIV-1 infected children with selected mutant chemokine receptor polymorphims CCR5-39353, 39356, and 39402 may exhibit better neurodevelopmental outcome than children with the wild type allele.
Llorente
Antolin
A
University of Maryland School of Medicine, (Mount Washington Pediatric Hospital), 1708 West Rogers Avenue, Suite 1141, Baltimore, MD 21209, USA. allorente@mwph.org
Brouwers
Pim
P
Thompson
Bruce
B
Cheng
Irene
I
Macmillan
Carol
C
Larussa
Phillip
P
Mofenson
Lynne
L
Blasini
Ileana
I
Chase
Cynthia
C
D015526:AIDS Dementia Complex / Q000235:genetics* / Q000635:transmission; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D015497:HIV-1; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*; D016019:Survival Analysis
C515334:CCR2 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine