|
CCR2 V64I (Chemokine receptor CCR2, Valine 64 Isoleucine, G190A on nucleotide level)The allelic variant of the chemokine receptor CCR2, CCR2 64I, which occurs at a frequency of about 10 %, has been shown to slow down progression rates after HIV-1 seroconversion for two to four years as compared to individuals homozygous for the wildtype allele CCR2-V64 (1, 2). The G-to-A polymorphism in the coding region of CCR2 causes a switch from valine to isoleucine at position 64 (2). The molecular mechanism resulting in protection of individuals bearing a mutant allele remain speculative, but is certainly independent of the CCR5-del32 genotype variant (2). Also in other diseases, the CCR2-64I allele has been described as a protective factor : In renal transplantation, the risk of acute transplant rejection was found significantly reduced (odds ratio 0.30) in recipients who possessed the CCR2-64I allele (3). Also, the extent of coronary artery calcifications was significantly lower in subjects with the CCR2-64I variant (V/I and I/I genotypes) than in subjects carrying 2 V64 alleles, even after adjustment for traditional risk factors (4). The presence of the CCR2-64I allele was also found to confer a lower risk for the development of sarcoidosis (adjusted odds ratio = 0.369 (5)).References (1) L.G. Kostrikis et al. A chemokine receptor CCR2 allele delays HIV-1 disease progression and is associated with a CCR5 promoter mutation. Nat Med 4 (1998) : 350-353 (PMID: 9500612)<Abstract> (2) M.W. Smith et al. Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Science 277 (1997) : 959-965 (PMID: 9252328)<Abstract> (3) Abdi R. et al. Chemokine receptor polymorphism and risk of acute rejection in human renal transplantation. J Am Soc Nephrol 2002 Mar;13(3):754-8 (PMID: 11856781)<Abstract> (4) Valdes A.M. et al. Val64Ile polymorphism in the C-C chemokine receptor 2 is associated with reduced coronary artery calcification. Arterioscler Thromb Vasc Biol 2002 Nov 1;22(11):1924-8 (PMID: 12426226)<Abstract> (5) Hizawa N. et al. The role of the C-C chemokine receptor 2 gene polymorphism V64I (CCR2-64I) in sarcoidosis in a Japanese population. Am J Respir Crit Care Med 1999; 159(6):2021-3 (PMID: 10351956)<Abstract> |