Polymorphisms in the CCR5 promoter region influence disease progression in perinatally human immunodeficiency virus type 1-infected children.
The effect of CC-chemokine receptor 5 (CCR5) promoter polymorphisms on the natural history of human immunodeficiency virus (HIV) disease was studied in 73 HIV-1-infected children. The CCR5(59338-59537) promoter haplotype, CCR5-59029A/G polymorphism, and CCR5Delta32 and CCR2-64I alterations were investigated. After exclusion of carriers of CCR5Delta32 or CCR2-64I, Kaplan-Meier analysis disclosed that children with the P1/P1(59353C,59356C,59402A) genotype progressed faster to disease than did children with other haplotypes (P=.016). When CCR2-64I carriers were included, this effect had borderline significance (P=.065) and was lost when CCR5Delta32 carriers were also considered (P=.387). The P1/P1 effect was strongest early after infection, when progression to disease was mainly associated with CCR5 coreceptor-using viruses. These results indicate that the P1/P1 genotype is predictive of rapid progression in HIV-1-infected children lacking CCR5Delta32 or CCR5-64I alleles. The observation of a linkage disequilibrium between P1 and 59029A might explain the previously reported association between 59029A homozygosity and rapid disease progression.
Ometto
L
L
Department of Oncology and Surgical Sciences, Oncology Section, AIDS Reference Center, Via Gattamelata 64, 35128 Padova, Italy.
Bertorelle
R
R
Mainardi
M
M
Zanchetta
M
M
Tognazzo
S
S
Rampon
O
O
Ruga
E
E
Chieco-Bianchi
L
L
De Rossi
A
A
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000235:genetics* / Q000635:transmission; D015497:HIV-1; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D015810:Linkage Disequilibrium; D008297:Male; D018743:Perinatal Care; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*
D019713:Receptors, CCR5