Frequency of CCR5Δ32 allele in healthy Bosniak population.

Grażyna Adler; Amina Valjevac; Karolina Skonieczna-Żydecka; Mirela Mackic-Djurovic; Miłosz Parczewski; Anna Urbańska; Nermin Nusret Salkic

doi:10.17305/bjbms.2014.3.102

Authors

Grażyna Adler The Department of Gerontobiology, Pomeranian Medical University, ul. Żołnierska 48, 71-210 Szczecin, Poland
Amina Valjevac Laboratory for Molecular Medicine, Center for Genetics, Medical Faculty, University Sarajevo, Cekalusa 90, 71 000 Sarajevo, Bosnia and Herzegovina
Karolina Skonieczna-Żydecka The Department of Gerontobiology, Pomeranian Medical University, ul. Żołnierska 48, 71-210 Szczecin, Poland
Mirela Mackic-Djurovic Laboratory for Molecular Medicine, Center for Genetics, Medical Faculty, University Sarajevo, Cekalusa 90, 71 000 Sarajevo, Bosnia and Herzegovina
Miłosz Parczewski Department of Infectious Diseases and Hepatology, Pomeranian Medical University, ul. Arkońska 4, 71-455 Szczecin, Poland
Anna Urbańska Department of Infectious Diseases and Hepatology, Pomeranian Medical University, ul. Arkońska 4, 71-455 Szczecin, Poland
Nermin Nusret Salkic Department of Gastroenterology and Hepatology, University Clinical Center Tuzla, Trnovac bb, 75 000 Tuzla, Bosnia and Herzegovina

DOI:

https://doi.org/10.17305/bjbms.2014.3.102

Keywords:

cytokine receptor, del32 variant, genetic epidemiology, HIV susceptibility

Abstract

Recent evidence has demonstrated the role of CCR5Δ32 in a variety of human diseases: from infectious and inflammatory diseases to cancer. Several studies have confirmed that genetic variants in chemokine receptor CCR5 gene are correlated with susceptibility and resistance to HIV infection. A 32-nucleotide deletion within the CCR5 reading frame is associated with decreased susceptibility to HIV acquisition and a slower progression to AIDS. Mean frequency of CCR5Δ32 allele in Europe is approximately 10%. The highest allele frequency is observed among Nordic populations (about 12%) and lower in the regions of Southeast Mediterranean (about 5%). Although the frequency of CCR5Δ32 was determined in numerous European populations, there is a lack of studies on this variant in the Bosnia and Hercegovina population. Therefore, the aim of our study was to assess the frequency of CCR5Δ32 allele in the cohort of Bosniaks and compare the results with European reports. CCR5Δ32 was detected by sequence-specific PCR in a sample of 100 healthy subjects from Bosnia and Herzegovina (DNA collected 2011-2013). Mean age of the cohort being 58.8 (±10.7) years, with 82% of women. We identified 17 heterozygotes and one mutant homozygote in study group, with mean ∆32 allele frequency of 9.5%. CCR5∆32 allele frequency among Bosniaks is comparable to that found in Caucasian populations and follows the pattern of the north-southern gradient observed for Europe. Further studies on larger cohorts with adequate female-to-male ratio are necessary.

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Author Biography

Grażyna Adler, The Department of Gerontobiology, Pomeranian Medical University, ul. Żołnierska 48, 71-210 Szczecin, Poland

The present study was performed in accordance with the ethical standards and the Declaration of Helsinki. Written informed consent was obtained from all participants.

References

Guergnon J, Combadiere C. Role of chemokines polymorphisms in diseases. Immunol Lett. 2012; 145(1-2):15-22.

Han SW, Sa KH, Kim SI, Lee SI, Park YW, Lee SS, et al. CCR5 gene polymorphism is a genetic risk factor for radiographic severity of rheumatoid arthritis. Tissue Antigens. 2012; 80(5):416-423.

D'Angelo R, Crisafulli C, Rinaldi C, Ruggeri A, Amato A, Sidoti A. CCR5Δ32 Polymorphism Associated with a Slower Rate Disease Progression in a Cohort of RR-MS Sicilian Patients. Mult Scler Int. 2011; 2011:15328.

Zheng B, Wiklund F, Gharizadeh B, Sadat M, Gambelunghe G, Hallmans G, et al. Genetic polymorphism of chemokine receptors CCR2 and CCR5 in Swedish cervical cancer patients. Anticancer Res. 2006; 26(5B):3669-3674.

Mueller A, Strange PG. The chemokine receptor, CCR5. Int J Biochem Cell Biol. 2004; 36(1):35-38.

Thelen M. Dancing to the tune of chemokines. Nat Immunol. 2001; (2):129-134.

Sandford B, Bown M, London N, Sayers R. The role of the CCR5 Δ32 polymorphism in abdominal aortic aneurysms. Int J Immunogenet. 2009; 36(4):199-205.

Murphy PM, Baggiolini M, Charo IF, Hebert CA, Horuk R, Matsushima K, et al. International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev. 2000; 52(1):145-176.

Libert F, Cochaux P, Beckman G, Samson M, Aksenova M, Cao A, et al. The deltaccr5 mutation conferring protection against HIV-1 in Caucasian populationshas a single and recent origin in Northeastern Europe. Hum Mol Genet. 1998; 7(3):399-406.

Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science 1996; 273(5283):1856-1862.

Venkatesan S, Petrovic A, Van Ryk DI, Locati M, Weissman D, Murphy PM. Reduced cell surface expression of CCR5 in CCR5Delta 32 heterozygotes is mediated by gene dosage, rather than by receptor sequestration.J Biol Chem. 2002; 277(3):2287-2301.

Liu Y, Liu FL, He Y, Li L, Li S, Zheng YT, et al. The genetic variation of CCR5, CXCR4 and SDF-1 in three Chinese ethnic populations. Infect Genet Evol. 2012; 12(5):1072-1078.

Pazzola G, Boiardi L, Casali B, Farnetti E, Nicoli D, Pipitone N, Padovano I, Caruso A, Catanoso M, Salvarani C. CC chemokine receptor 5 polymorphism in Italian patients with giant cell arteritis. Mod Rheumatol. 2013; 23(5):851-855.

Laplana M, Fibla J. Distribution of functional polymorphic variants of inflammation-related genes RANTES and CCR5 in long-lived individuals. Cytokine. 2012; 58(1):10-13.

Guergnon J, Combadiere C. Role of chemokines polymorphisms in diseases. Immunol Lett. 2012; 145(1-2):15-22.

Lucotte G. Distribution of the CCR5 gene 32-basepair deletion in West Europe. A hypothesis about the possible dispersion of the mutation by the Vikings in historical times. Hum Immunol 2001; 62: 933-6.

Scott S and Duncan CJ. Biology of plaques: Evidence from Historical Populations. Cambridge University Press, Cambridge, p. 434.

Stephens JC, Reich DE, Goldstein DB, Shin HD, Smith MW, Carrington M, et al. Dating the origin of the CCR5-Delta32 AIDS-resistance allele by the coalescence of haplotypes. Am J Hum Genet. 1998; 62(6):1507-1515.

Kostulas N, Markaki I, Kostulas V, Hillert J, Kostulas K. Common CCR 5 polymorphism in stroke: the CCR 5 delta32 polymorphism differentiates cardioembolism from other aetiologies of ischaemic cerebrovascular diseases. Scand J Immunol. 2009; 70(5):475-480.

Savarrio L, Donati M, Carr C, Kinane DF, Berglundh T. Interleukin-24, RANTES and CCR5 gene polymorphisms are not associated with chronic adult periodontitis. J Periodontal Res. 2007; 42(2):152-158.

Baragiotta A, Floreani A, Agarwal K, Venturi C, Craggs A, Jones DE, et al. Chemokine receptor 5 and primary biliary cirrhosis: a two-centre genetic association study. Liver Int. 2004; 24(6):646-650.

Leboute AP, de Carvalho MW, Simoes AL. Absence of the deltaccr5 mutation in indigenous populations of the Brazilian Amazon. Hum Genet. 1999; 105(5):442-443.

Salem AH, Batzer MA. Distribution of the HIV resistance CCR5-Delta32 allele among Egyptians and Syrians. Mutat Res. 2007; 616(1-2):175-180.

Qijian S, Zhidan M, Ning Z, Shuzhi W, Xin X, Hao L. Distribution of CCR5-{delta}32, CCR2-64I, and SDF1-3'A in Guangxi Zhuang population. J Int Assoc Physicians AIDS Care (Chic). 2010; 9(3):145-149.

Rector A, Vermeire S, Thoelen I, Keyaerts E, Struyf F, Vlietinck R, et al. Analysis of the CC chemokine receptor 5 (CCR5) delta-32 polymorphism in inflammatory bowel disease. Hum Genet. 2001; 108(3):190-193.

Al-Jaberi SA, Ben-Salem S, Messedi M, Ayadi F, Al-Gazali L, Ali BR. Determination of the CCR5∆32 frequency in Emiratis and Tunisians and the screening of the CCR5 gene for novel alleles in Emiratis. Gene. 2013; 529(1):113-118.

Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, et al. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 1996; 382:722-725.

Huang Y, Paxton WA, Wolinsky SM, Neumann AU, Zhang L, He T, Kang S, et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med 1996; 2:1240-1243.

Sellebjerg F, Kristiansen TB, Wittenhagen P, Garred P, Eugen-Olsen J, Frederiksen JL, et al. Chemokine receptor CCR5 in interferon-treated multiple sclerosis. Acta Neurol Scand. 2007; 115(6):413-418.

Petrek M, Cermakova Z, Hutyrova B, Micekova D, Drabek J, Rovensky J, Bosak V. CC chemokine receptor 5 and interleukin-1 receptor antagonist gene polymorphisms in patients with primary Sjögren's syndrome. Clin Exp Rheumatol. 2002; 20(5):701-703.

Dordevic V, Timotijevic G, Pruner I, Radojkovic D, Milanovic B, Milijkovic D. The frequency of allele CCR5∆32 in a Serbian population. J Med Biochem. 2013; 32(4):368-374.

Ristic S, Starcevic-Cizmarevic N, Brajevovic-Milic B, Crnic-Martinovic M, Kapovic M. frequency of CCR5 gene 32-basepair deletion in Croatian normal population. Croat Med J. 2005; 46:693-694.

Atzeni F, Boiardi L, Casali B, Farnetti E, Nicoli D, Sarzi-Puttini P, et al. CC chemokine receptor 5 polymorphism in Italianpatients with Behcet’s disease. Rheumatology (Oxford). 2012; 51(12):2141-2145.

Biloglav Z, Zgaga L, Smoljanović M, Hayward C, Polasek O, Kolcić I, et al. Historic, Demographic, and Genetic Evidence for Increased Population Frequencies of CCR5Δ32 Mutation in Croatian Island Isolates after Lethal 15th Century Epidemics. Croat Med J. 2009; 50(1):34-42.

Ghilardi G, Biondi ML, Turri O, Pateri F, d'Eril GM, Scorza R. Genetic control of chemokines in severe human internal carotid artery stenosis. Cytokine. 2008; 41(1):24-8.

Smoljanović M, Ristić S, Hayward C. Historic Exposure to Plague and Present-day Frequency of CCR5del32 in Two Isolated Island Communities of Dalmatia, Croatia. Croat Med J. 2006; 47(4):579-584.

Gambelunghe G, Ghaderi M, Gharizadeh B, Brozzetti A, Tortoioli C, Del Sindaco P, et al. Lack of association of human chemokine receptor gene polymorphisms CCR2-64I and CCR5 delta32 with autoimmune Addison’s disease. Eur J Immunogenet. 2004; 31(2):73-76.

Galimberti D, Fenoglio C, Lovati C, Gatti A, Guidi I, Venturelli E, et al. CCR2-64I polymorphism and CCR5D32 deletion in patients with Alzheimer’s disease. J Neurol Sci. 2004; 225(1-2):79-83.

Carmona FD, Rodríguez-Rodríguez L, Castaneda S, Miranda-Filloy JA, Morado IC, Narváez J, et al. Role of the CCR5/32CCR5 polymorphism in biopsy-proven giant cell arteritis. Hum Immunol. 2011; 72(5):458-61.

Veloso S, Olona M, García F, Domingo P, Alonso-Villaverde C, Broch M, et al. Eefsefaercch tar toiclfe TNF-α genetic variants and CCR5Δ32 on the vulnerability to HIV-1 infection and disease progression in Caucasian Spaniards. BMC Med Genet. 2010; 11:63.

Vilades C, Broch M, Plana M, Domingo P, Alonso-Villaverde C, Pedrol E, et al. Effect of Genetic Variants of CCR2 and CCL2 on the Natural History of HIV-1 Infection CCL2-2518GG Is Overrepresented in a Cohort of Spanish HIV-1 Infected Subjects. J Acquir Immune Defic Syndr. 2007; 44(2):132-138.

Huerta C, Alvarez V, Mata IF, Coto E, Ribacoba R, Martínez C, et al. Chemokines (RANTES and MCP-1) and chemokine-receptors (CCR2 and CCR5) gene polymorphisms in Alzheimer’s and Parkinson’s disease. Neurosci Lett. 2004; 370(2-3):151-154.

Ruiz-Ferrer M, Barroso N, Antinolo G, Aguilar-Reina J. Analysis of CCR5-D32 and CCR2-V64I polymorphisms in a cohort of Spanish HCV patients using Real-time Polymerase Chain Reaction and Fluorescence Resonance Energy Transfer technologies. J Viral Hepat. 2004; 11(4):319-323.

Gawron AJ, Fought AJ, Lissowska J, Ye W, Zhang X, Chow WH, et al. Polymorphisms in chemokine and receptor genes and gastric cancer risk and survival in a high risk Polish population. Scand J Gastroenterol. 2011; 46(3):333-340.

Parczewski M, Leszczyszyn-Pynka M, Kaczmarczyk M, Adler G, Binczak-Kuleta A, Loniewska B, et al. Sequence variants of chemokine receptor genes and susceptibility to HIV-1 infection. J Appl Genet. 2009; 50(2):159-66.

Fischer A, Valentonyte R, Nebel A, Nothnagel M, Müller-Quernheim J, Schürmann M, et al. Female-specific association of C-C chemokine receptor 5 gene polymorphisms with Löfgren’s syndrome. J Mol Med (Berl). 2008; 86(5):553-561.

Zawicki P, Witas HW. HIV-1 protecting CCR5-D32 allele in medieval Poland. Infect Genet Evol. 2008; 8(2):146-151.

Mlynarski WM, Placha GP, Wolkow PP, Bochenski JP, Warram JH, Krolewski AS. Risk of Diabetic Nephropathy in Type 1 Diabetes IsAssociated With Functional Polymorphisms in RANTES Receptor Gene (CCR5) - a Sex-Specific Effect. Diabetes. 2005; 54(11):3331-3335.

Wasmuth HE, Werth A, Mueller T, Berg T, Dietrich CG, Geier A, et al. CC chemokine receptor 5 D32 polymorphism in two independent cohorts of hepatitis C virus infected patients without hemophilia. J Mol Med (Berl). 2004; 82(1):64-69.

Folwaczny M, Glas J, Török HP, Fricke K, Folwaczny C. Prevalence of the chemokine receptor CCR5-32 gene mutation in periodontal disease. Clin Immunol. 2003; 109(3):325-329.

Herfarth H, Pollok-Kopp B, Göke M, Press A, Oppermann M. Polymorphism of CC chemokine receptors CCR2 and CCR5 in Crohn’s disease. Immunol Lett. 2001; 77(2):113-117.

Dean M, Carrington M, O'Brien SJ. Balanced polymorphism selected by genetic versus infectious human disease. Annu Rev Genomics Hum Genet. 2002; 3:263-92.

Petrek M, Gibejova A, Drabek J, Mrazek F, Kolek V, Weigl E, et al. CC Chemokine Receptor Gene Polymorphisms in Czech Patients with Pulmonary Sarcoidosis. Immunol Lett. 2002; 80(3):189-193.

Ryabov GS, Kazennova EV, Bobkova MR, Bobkov AF. Prevalence of Alleles Associated with HIV Resistance in Russia. Genet Test. 2004; 8(1):73-76.