Scientific background:

Summary: The importance of this gene is related to a known mutation that decreases the development of AIDS in HIV infected patients.

Gene: 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.

Pathology: 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 iinfluence 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.

Clinical signs: 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.

Epidemiology: 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.

Interpretation: HIV infected patients wich are heterozygous for this mutation will develop the typical symtomes of AIDS later on. Homozygous paitients may never become ill.

Test strategy: 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.

Methodology:

	clinical test	Method		Hotspot sequencing
		Turn-around time		5 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	Only in the region of interest, known and new missense, nonsense and splice mutations can be detected.
	clinical test	Method		Fragment analysis
		Turn-around time		5 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	Only the target mutation is detected all other genetic variations, though possibly important they may be, are missed.

Literature: 

Tang J et al. (2002) Distribution of chemokine receptor CCR2 and CCR5 genotypes and their relative contribution to human immunodeficiency virus type 1 (HIV-1) seroconversion, early HIV-1 RNA concentration in plasma, and later disease progression.
Knudsen TB et al. (2001) Adverse effect of the CCR5 promoter -2459A allele on HIV-1 disease progression.
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.