Polymorphism in the CCR5 gene promoter and HIV-1 infection in North Indians.
The clinical course and outcome of human immunodeficiency virus-1 (HIV-1) infection are highly variable among individuals. CCR5 is the primary coreceptor that mediates entry of HIV-1 (R5) into permissive host cells. In this study, five SNPs (59029G/A, 59353T/C, 59356C/T, 59402A/G, and 59653C/T) in the promoter region and a deletion of 32 bp (Delta32) in the CCR5 gene were evaluated in 180 chronically HIV-1-infected North Indians. The study showed the following: (1) the protective CCR5 Delta32 allele was absent; (2) the frequency of CCR5*59402A allele in the HIV-infected people (66.4%) was higher than in healthy subjects (57.1%, p = 0.027) and in the CDC stage C patients (76%) versus stages A and B patients together (60%; p = 0.002); (3) homozygous CCR5*59402 AA genotype was significantly increased in the seropositive subjects (46.1%) compared with healthy control subjects (30.2%; p = 0.008) and in the CDC stage C patients (59.2%) compared with stage A and B subjects (37.6%, p = 0.007); and (4) an increased frequency of homozygous ACCAC haplotype was present in the seropositive stage C patients (32.4%) versus 15.6% in patients in stages A plus B (p = 0.013). These observations suggest an association of CCR5*59402A with increased likelihood of acquisition of HIV-1 and development of AIDS in the Asian Indian population. Further studies are required to confirm these findings and understand the effect of CCR5 polymorphisms on the outcome of HIV-1 infection.
Kaur
Gurvinder
G
Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.
Singh
P
P
Rapthap
C C
CC
Kumar
N
N
Vajpayee
M
M
Sharma
S K
SK
Wanchu
A
A
Mehra
N K
NK
D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002648:Child; D002675:Child, Preschool; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006679:HIV Seropositivity / Q000097:blood; D015497:HIV-1; D006239:Haplotypes; D006801:Humans; D007194:India; D018655:Lymphocyte Count; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*
D019713:Receptors, CCR5