Polymorphisms in CCR5 chemokine receptor gene in Japan
H Liu1, E E Nakayama, I Theodorou
1Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
International Journal of Immunogenetics
|September 12, 2007
Summary
Genetic variations in the CC chemokine receptor 5 (CCR5) gene influence human immunodeficiency virus type 1 (HIV-1) susceptibility. Novel CCR5 promoter haplotypes associated with rapid acquired immune deficiency syndrome (AIDS) progression were identified in Asian populations.
Area of Science:
- Genetics
- Immunology
- Virology
Background:
- Mutations in the CC chemokine receptor 5 (CCR5) gene can affect protein function, influencing chemokine signaling and susceptibility to human immunodeficiency virus type 1 (HIV-1) infection.
- CCR5 is a key co-receptor for HIV-1 entry into host cells.
Purpose of the Study:
- To systematically survey natural sequence variations in the CCR5 gene and CCR2V64I in Japanese and Thai populations.
- To evaluate the effects of identified variations on CCR5 promoter activity.
- To investigate CCR5-CCR2 haplotype structures and their association with HIV-1 infection progression.
Main Methods:
- Systematic sequencing of an 8.1-kb region of the CCR5 gene and CCR2V64I in Japanese and Thai subjects.
- Analysis of CCR5 promoter activity in relation to identified genetic variations.
- Haplotype analysis of CCR2 and CCR5 genes.
Main Results:
- Two novel non-synonymous substitutions were identified in the Japanese CCR5 gene, distinct from the 32-bp deletion common in Caucasians.
- A specific CCR5 promoter haplotype (G allele at -2852) found in Japanese and Thai individuals was associated with rapid acquired immune deficiency syndrome (AIDS) progression in HIV-1-infected individuals.
- Nearly all non-synonymous CCR5 polymorphisms in Japanese subjects were linked to haplotypes exhibiting elevated promoter activity.
Conclusions:
- Novel CCR5 genetic variations and haplotype structures exist in Asian populations, differing from those in Caucasian and African-American populations.
- The identified CCR5 promoter haplotype is a significant genetic factor associated with accelerated AIDS progression.
- These findings suggest a potential evolutionary selective pressure favoring lower CCR5 expression levels.
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