The frequency of CCR5 promoter polymorphisms and CCR5 32 mutation in Iranian populations

Document Type: Review Article


1 Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

2 Department of Immunology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

3 Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran


Evidence showed that chemokines serve as pro-migratory factors for immune cells. CCL3, CCL4 and CCL5, as the main CC  chemokines subfamily members, activate immune cells through binding to CC chemokine receptor 5 or CCR5. Macrophages, NK cells and T lymphocytes express CCR5 and thus, affected CCR5 expression or functions could be associated with altered immune responses. Deletion of 32 base pairs (D 32) in the exon 1 of the CCR5 gene, which is known as CCR5 D 32 mutation causes down regulation and malfunction of the molecule. Furthermore, it has been evidenced that three polymorphisms in the promoter region of CCR5 modulate its expression. Altered CCR5 expression in microbial infection and immune related diseases have been reported by several researchers but the role of CCR5 promoter polymorphisms and CCR5 D 32 mutation in Iranian patients suffering from these diseases are controversial. Due to the fact that Iranian people have different genetic backgrounds compared to other ethnics, hence, CCR5 promoter polymorphisms and CCR5 D 32 mutation association with the diseases may be different in Iranian patients. Therefore, this review addresses the most recent information regarding the prevalence as well as association of the mutation and polymorphisms in Iranian patients with microbial infection and immune related diseases as along with normal population.


1.  Chisari FV, Isogawa M, Wieland SF. Pathogenesis of hepatitis B virus infection. Pathol Biol (Paris) 2010; 58:258-266.

2. Miyara M, Wing K, Sakaguchi S. Therapeutic approaches to allergy and autoimmunity based on FoxP3+ regulatory T-cell activation and expansion. J Allergy Clin Immunol 2009; 123:749-755.

3.  Blanpain C, Migeotte I, Lee B, Vakili J, Doranz BJ, Govaerts C, et al. CCR5 binds multiple CC-chemokines: MCP-3 acts as a natural antagonist. Blood 1999; 94:1899-1905.

4. Arababadi MK, Pourfathollah AA, Jafarzadeh A, Hassanshahi G. Decreased expression of CCR5 on the NK cells in occult HBV infected patients. Lab Med 2010; 41:735-738.

5.  Jin Q, Agrawal L, Meyer L, Tubiana R, Theodorou I, Alkhatib G. CCR5Delta32 59537-G/A promoter polymorphism is associated with low translational efficiency and the loss of CCR5Delta32 protective effects. J Viro. 2008; 82:2418-2426.

6.  Singh H, Sachan R, Jain M, Mittal B. CCR5-Delta32 polymorphism and susceptibility to cervical cancer: association with early stage of cervical cancer. Oncol Res 2008; 17:87-91.

7.  Nahon P, Sutton A, Rufat P, Simon C, Trinchet JC, Gattegno L, et al. Chemokine system polymorphisms, survival and hepatocellular carcinoma occurrence in patients with hepatitis C virus-related cirrhosis. World J Gastroenterol 2008;14:713-719.

8. Ghorban K, Dadmanesh M, Hassanshahi G, Momeni M, Zare-Bidaki M, Arababadi MK, et al. Is the CCR5 Delta 32 mutation associated with immune system-related diseases? Inflammation 2013; 36:633-642.

9.  Guerini FR, Delbue S, Zanzottera M, Agliardi C, Saresella M, Mancuso R, et al. Analysis of CCR5, CCR2, SDF1 and RANTES gene polymorphisms in subjects  with HIV-related PML and not determined leukoencephalopathy. Biomed Pharmacother 2008; 62:26-30.

10. Abousaidi H, Vazirinejad R, Arababadi MK, Rafatpanah H, Pourfathollah AA, Derakhshan R, et al. Lack of association between chemokine receptor 5 (CCR5) delta32 mutation and pathogenesis of asthma in Iranian patients. South Med J 2011; 104:422-425.

11.  Chang HY, Ahn SH, Kim DY, Shin JS, Kim YS, Hong SP, et al. Association between CCR5 promoter polymorphisms and hepatitis B virus infection. Korean J Hepatol 2005; 11:116-124.

12. Al-Abdulhadi SA, Al-Rabia MW. Linkage and haplotype analysis for chemokine receptors clustered on chromosome 3p21.3 and transmitted in family pedigrees with asthma and atopy. Ann Saudi Med 2010; 30:115-122.

13.  Lehner T. The role of CCR5 chemokine ligands and antibodies to CCR5 coreceptors in preventing HIV infection. Trends Immunol 2002; 23:347-351.

 14.  Ahmadabadi BN, Hassanshahi G, Khoramdelazad H, Mirzaei V, Sajadi SMA, Hajghani M, et al. Down-regulation of CCR5 expression on the peripheral blood CD8+ T cells of South-Eastern Iranian patients with chronic hepatitis B infection. Inflammation  2013; 36:136-140.

15.  Song JK, Park MH, Choi DY, Yoo HS, Han SB, Yoon do Y, et al. Deficiency of C-C chemokine receptor 5 suppresses tumor development via inactivation of NF-kappaB and upregulation of IL-1Ra in melanoma model. PLoS One 2012; 7:e33747.

16.  Kuipers HF, Biesta PJ, Montagne LJ, van Haastert ES, van der Valk P, van den Elsen PJ. CC chemokine receptor 5 gene promoter activation by the cyclic AMP response element binding transcription factor. Blood 2008; 112:1610-1619.

17.  Blanpain C, Libert F, Vassart G, Parmentier M. CCR5 and HIV infection. Receptors Channels 2002; 8:19-31.

18.  Sorce S, Myburgh R, Krause KH. The chemokine receptor CCR5 in the central nervous system. Prog Neurobiol 2011; 93:297-311.

19. Wong M, Uddin S, Majchrzak B, Huynh T, Proudfoot AE, Platanias LC, et al. Rantes activates Jak2 and Jak3 to regulate engagement of multiple signaling pathways in T cells. J Biol Chem 2001; 276:11427-11431.

20. Gharagozloo M, Doroudchi M, Farjadian S, Pezeshki AM, Ghaderi A. The frequency of CCR5Delta32 and CCR2-64I in southern Iranian normal population. Immunol Lett 2005; 96:277-281.

21.  Azmandian J, Mandegary A, Saber A, Torshabi M, Etminan A, Ebadzadeh MR, et al. Chemokine receptor 2-V64I and chemokine receptor 5-Delta32 polymorphisms and clinical risk factors of delayed graft function and acute rejection in kidney transplantation. Iran J Kidney Dis 2012; 6:56-62.

22.  Khademi B, Razmkhah M, Erfani N, Gharagozloo M, Ghaderi A. SDF-1 and CCR5 genes polymorphism in patients with head and neck cancer. Pathol Oncol Res 2008; 14:45-50.

23.  Khorram Khorshid HR, Manoochehri M, Nasehi L, Ohadi M, Rahgozar M, Kamali R. CCR2-64i and CCR5 Delta32 polymorphisms in patients with late-onset Alzheimer's disease; a study from Iran. Iran J Basic Med Sci 2012; 15:937-944.

24.  Mojtahedi Z, Ahmadi SB, Razmkhah M, Azad TK, Rajaee A, Ghaderi A. Association of chemokine receptor 5 (CCR5) delta32 mutation with Behcet's disease is dependent on gender in Iranian patients. Clin Exp Rheumatol 2006; 24:S91-94.

25. M. AMS,  ؟؟Rezazadeh M, Gharesouran j, Yeghaneh T, Farhoudi M, Ayromlou H, et al. Association of
CCR2 gene but not CCR5 gene polymorphisms with Alzheimer's disease. J Sci Islam Rep Iran 2011; 22:111-116.

26. Arababadi MK, Pourfathollah AA, Jafarzadeh A, Hassanshahi G, Mohit M, Hajghani M, et al. Peripheral blood CD8+ T cells CCR5 expression and its D 32 mutation in Iranian patients with occult hepatitis B infection. LabMed 2010; 41:226-230

27.  Khorramdelazad H, Hakimizadeh E, Hassanshahi G, Rezayati M, Sendi H, Arababadi MK. CCR5 D 32 mutation is not prevalent in iranians with chronic HBV infection. J Med Virol 2013; 9999:1-5.

28. Arababadi MK, Naghavi N, Hassanshahi G, Mahmoodi M. Is CCR5-Delta32 mutation associated with diabetic nephropathy in type 2 diabetes? Ann Saudi Med 2009; 29:413.

29.  Arababadi MK, Hassanshahi G, Azin H, Salehabad VA, Araste M, Pourali R, et al. No association between CCR5 D 32 mutation and multiple sclerosis in patients of south-eastern of Iran. LabMed 2010; 1:31-33.

30.  Shahbazi M, Ebadi H, Fathi D, Roshandel D, Mahamadhoseeni M, Rashidbaghan A, et al. CCR5-delta 32 allele is associated with the risk of developing multiple sclerosis in the Iranian population. Cell Mol Neurobiol 2009; 29:1205-1209.

31.  Abdi R, Tran TB, Sahagun-Ruiz A, Murphy PM, Brenner BM, Milford EL, et al. Chemokine receptor polymorphism and risk of acute rejection in human renal transplantation. J Am Soc Nephrol 2002; 3:754-758.

32.  Omrani MD, Mokhtari MR, Tagizadae A, Bagheri M, Ahmad-Poor P. Association of CCR5-59029 A/G and CCR2-V64I variants with renal allograft survival. Iran J Immunol 2008; 5:201-206.