The CCR5 gene encodes a chemokine receptor expressed on lymphocytes and used by several viruses to enter the cell. Genetic variants are associated with susceptibility to several virus infections and type 1 diabetes.
The frequency of CCR5 32bp deletion exhibits a gradient from North to South. This mutation can not be found in Asia. The first occurance of this mutation is dated 150.000 years ago.
The gene CCR5 is about 6kb in size. It is localized on chromosome 3 at position 3p21. The gene consists of 4 exons but only the very large exon 4 is translated. The exons 2 and 3 are fused. This way only 2 introns exist.
The so called HIV resistance has the main clinical importance. It occurse in cases where a mutation destroys the function of the receptor. Most common in our populations is the CCR5 32bp deletion.
The protein product of that gene is a receptor for chemokines, so this gene is tighly connected to inflammatory processes and it can modify its sequence and apperance. Many of such modification have been investigated in clinical settings and animal models. The influence on manifestation of AIDS after HIV infection is the most important one. But some clinical data suggest that there is an influence on course and severity of glomerulonephritis, IgA nephropathy in particular.
Patients with a higher risk for HIV exposition (prostitutes, druggies, physicians, nurces, patients requiring recurrent blood transfusions).To estimate prognosis this test may be used in HIV infected patients together with virus load and CD4/CD8-relation.
HIV infected patients which are heterozygous for this mutation will develop the typical symtomes of AIDS later on. Homozygous paitients may never become ill.
Clinic | Method | Carrier testing |
Turnaround | 5 days | |
Specimen type | genomic DNA |
Clinic | Method | Massive parallel sequencing |
Turnaround | 25 days | |
Specimen type | genomic DNA |
Clinic | Method | Genomic sequencing of the entire coding region |
Turnaround | 20 days | |
Specimen type | genomic DNA |
Clinic | Method | Target mutation analysis |
Turnaround | 20 days | |
Specimen type | genomic DNA |
Clinic | Method | Multiplex Ligation-Dependent Probe Amplification |
Turnaround | 25 days | |
Specimen type | genomic DNA |
HIV resistance | ||||
AIDS progression | ||||
IFNG | ||||
CCR5 | ||||
CXCR1 | ||||
HIV-1 viremia susceptibility | ||||
HLA-C | ||||
HIV1 susceptibility | ||||
IL10 | ||||
1. |
Knudsen TB et al. (2001) Adverse effect of the CCR5 promoter -2459A allele on HIV-1 disease progression. |
2. |
Ioannidis JP et al. (2001) Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data. |
4. |
NCBI article NCBI 1234 |
5. |
OMIM.ORG article Omim 601373 |
6. |
Orphanet article Orphanet ID 324270 |
7. |
Wikipedia article Wikipedia EN (CCR5) |