Frequency of CCR5Δ32 allele in healthy Bosniak population.

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.

Frequency of CCR5Δ32 allele in healthy Bosniak population.

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Published

2014-08-28

How to Cite

1.
Adler G, Valjevac A, Skonieczna-Żydecka K, Mackic-Djurovic M, Parczewski M, Urbańska A, Salkic NN. Frequency of CCR5Δ32 allele in healthy Bosniak population. Biomol Biomed [Internet]. 2014Aug.28 [cited 2023Mar.26];14(3):150-4. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/150

Issue

Vol. 14 No. 3 (2014)

Section

Molecular Biology

INTRODUCTION

Chemokines are cytokines crucial for leukocyte migration into inflammatory sites, where they stimulate cellular differentiation or activation. Additionally, their role in the pathogenesis of several immune-mediated diseases has been recognized [1-3]. Chemokines are divided based on the tertiary structure and cysteine placement near the N-terminus with two major subfamilies. One major chemokine subfamily is called “CXC” because the two amino acids nearest the N-termini of these proteins are separated by a single amino acid. On the other hand, second major subfamily is called “CC” because these two cysteines are adjacent [4,5].

One of the most commonly studied chemokine receptors is CCR5- a G protein coupled receptor inhibiting cAMP production, stimulating of Ca2+ ion release, and being the activator of MAP and Jun-N-terminal kinases [6].

In vitro studies identified potent CC-chemokine activators of CCR5 i.e. CCL3 (chemokine ligand 3, also known as macrophage inflammatory protein-1a), CCL4 (macrophage inflammatory protein-1b) and CCL5 (also known as RANTES - regulated on activation normal T cell expressed and secreted) [7].

Chemokine receptor CCR5 was cloned in 1996 and is encoded by CMKBR gene located on 3p21.31 [8,9]. CCR5 gene is polymorphic and these DNA alterations might affect gene expression and thereby protein function [10]. A 32 base pair deletion (CCR5Δ32, CCR5del32) within the CCR5 gene leads to a frame shift and loss of receptor function as well as inability to bind the specific ligands [11]. The CCR5 receptor is a major entry site for macrophage-tropic (CCR5 tropic) HIV-1 strains into host cells. CCR5Δ32/Δ32 homozygotes, lacking functional CCR5, are completely protected against infections with these HIV strains. Clinically it was shown that CCR5Δ32 allele is not only associated with decreased susceptibility to HIV infection, but is also linked to the delay in the progression towards AIDS [12]. Additionally, recent studies have confirmed the protective role of CCR5Δ32 allele with the course of certain diseases including hepatitis C, multiple sclerosis, acute myocardial infarction, atherosclerosis and rheumatoid arthritis [1-3, 13, 14]. Furthermore, the recently reported fact, that this allele is a risk factor for clinical manifestations of the West Nile virus infection, is tremendously interesting [15].

The frequency of CCR5Δ32 allele has been extensively studied in Europe and worldwide. Several hypotheses regarding CCR5Δ32 origin and persistence in the human population have been proposed. Lucotte et al. suggest that the CCR5Δ32 spread with the Vikings [16]. In this case, this would result in lower mutated allele prevalence in the areas where their expansion was limited: Balkans and South of Europe. An alternative hypothesis administered bubonic plague and viral diseases e.g. smallpox or viral hemorrhagic diseases, Ebola or Marburg viruses as the cause of CCR5Δ32 spread [17, 18].

This genetic mutation is most commonly found in populations of European ancestry being rare among other populations. Among Caucasians, it is the most prevalent in Sweden and Great Britain (12.7 and 12.3%, respectively) [4, 6, 19-21]. This allele has not been found, or is almost absent among South American native Indians (0%), Chinese cohorts (0%) and Egyptians (0.6%) [22-24].

To the best of our knowledge there are no data of this variant in the Bosniak population, which would complement the gaps in epidemiology European frequency of Δ32 allele CCR5.

We also wanted to fill the gaps for polymorphism CCR5 (decreased susceptibility to HIV infection among subjects with Δ32 allele) because Bosnia and Herzegovina is a country progressively opening to tourism. Therefore, the aim of our study was to assess genetic epidemiological data in the cohort of Bosniaks.

MATERIALS AND METHODS

Subjects

The study group consisted of 100 healthy Bosniaks, inhabitants from Bosnia and Herzegovina aged from 24-82 (mean: 58.8±10.7) years. There were 18 males and 82 females in the study group. Samples were collected at the Laboratory for Molecular Medicine, Center for Genetics, Faculty of Medicine, University of Sarajevo and Department of Gastroenterology and Hepatology, University Clinical Center Tuzla (in 2011-2013). Sample collection was focused on the buccal swabs and venous blood containing EDTA (anticoagulant).

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

DNA extracting and genotyping of CCR5Δ32

Genomic DNA from buccal swabs was extracted by PrepFilerTM Forensic DNA Extraction Kit (Life Technologies USA). QIAamp DNA Blood Mini Kit (QIAGEN, Hilden, Germany) was used to extract genomic DNA from whole blood samples. The extraction was performed following to the manufacturer’s protocols. Samples of DNA were stored at 4ºC for further analyses.

For the analysis of CCR5Δ32 mutation, sequence specific polymerase chain reaction (PCR) was run using the following primer pair: forward 5’-GCGTCTCTCCCAGGAATCATC-3’ and reverse 5’-GGTGAAGATAAGCCTCACAGCC-3’ (TIB MOL BIOL, Poznań, Poland). The protocol of amplification was previously described [25]. All resulting reaction products were electrophoresed on a 3% agarose gel (Agarose DNA Grade Electran) stained with DNA-star dye (Lonza, Inc, Rockland, USA), and visualized under UV light. The wild type and mutant Δ32 allele were detected as 242 and 210 base pair fragments, respectively (Figure 1). We verified the correctness of results by performing re-genotyping of randomly selected samples. All results were reliable.

FIGURE 1: Genotyping of theΔ32 polymorphism in the CCR5 gene. Line 1- pUC Mix Marker 8, ready to use (Fermentas, Latvia). Lines- 1, 6, 7, 8 - wt/wt genotype. Line 3, 4- wt/Δ32 genotype. Line 5- Δ32/Δ32 genotype

RESULTS

This is an epidemiologic study of the Bosniak population with the aim of determining the frequencies of CCR5Δ32 allele known to be associated with susceptibility and resistance to HIV infection. CCR5Δ32 allele frequency was determined in 100 healthy Bosniaks with identification of 17% CCR5 wt/Δ32 heterozygotes and 1% Δ32/Δ32 homozygotes. The results were conforming to the expected Hardy-Weinberg equilibrium (χ2 = 0.013; p = 0.909), and overall CCR5 Δ32 allele frequency in the group was 9.5%.

DISCUSSION

Study of the inter-population differences in the distribution of the key genetic variation, including CCR5∆32 mutation, commonly associated with diseases susceptibility and diseases progression provides vital insight into human molecular epidemiology. This study is filling the gaps in the knowledge on the human genetic variation for European countries. We also wanted to fill the gaps for polymorphism CCR5, despite the fact that the HIV infection is still uncommon among Bosniaks, since Bosnia and Herzegovina is a country progressively opening to tourism. Distribution of the CCR5Δ32 variant in the studied group is in accordance to the frequencies observed for the Caucasian populations. Its mean frequency among subjects of European descent is around 10%, with a North to South decreasing gradient. The only exception to this gradient was a population of Ashkenazi Jews, where observed CCR5Δ32 allele frequency was approximately 20%, probably due to a founder effect or genetic drift [26, 27]. In the normal Caucasian population, the genotype frequencies are approximately 1% for Δ32/Δ32 and between 10 and 15% for wt/Δ32 heterozygotes [28, 29].

The highest allele frequencies are observed among North European populations - for example in Denmark being 12.9% (n=105), Sweden 12.7% (n=1057) and Great Britain 12.3% (n=367), but also a high prevalence of the mutant allele was observed in Slovakia 14.4% (n =335) [4,6,19-21,29, 30]. The CCR532 allele frequency among European populations decreases in the Southern Europe being 4.6% in Serbia (n=352), 5.0% in Southeast Mediterranean, Croatia and Italy (n=1443, 1255 respectively) [13,21,31-38] and 7% in Spain (n=1242) [14,39-43]. Similar studies conducted from Germany and Poland showed that CCR5Δ32 allele frequency is approximately 10.0% [44-51].

Results of this study should be compared to the neighboring population of Croats where the frequency of the CCR5∆32 allele was found to be 5% (n=1443) and Serbs (n=352) 4.6% [31, 32, 34,36]. Allele frequency observed in our report was notably higher for the Bosniaks. The frequency of the CCR5∆32 allele among cohort from Bosnia and Herzegovina was also higher than that reported for Italy (5%) [13, 21, 31, 33, 35, 37, 38].

On the other hand, in our study it was found that the CCR5∆32 allele frequency among Bosniaks was comparable to that found in other North-European Slavic Caucasians: Poles (10.0%, n=1049), Czechs (10.8%, n=933), Russians (9.1%, n=171) and Slovenes (8.3%, n=495) [18, 44, 45, 47, 48, 50, 52- 54]. This value approximately agrees with the north-south gradient of distribution observed for Europe: Sweden (12.7%), Great Britain (10.9%), Germany (10.3%), Poland (10.0%) and Bosnia and Herzegovina (9.5%) and supports the hypothesis of a European origin of this allele and its introduction to the continent through migration [4, 6, 19-21, 44-50] (Figure 2).

FIGURE 2: Frequency of the CCR5∆32 allele in defined populations

CONCLUSION

CCR5∆32 allele frequency among Bosniaks was found to be 9.5% and is comparable to that found in Caucasian populations following the pattern of the north-southern gradient observed for Europe. Further studies on larger cohorts with adequate female-to-male ratio are necessary to confirm a frequency of allele CCR5∆32 in the cohort of Bosniaks. In our opinion it would be interesting to examine and to fill the gaps in the genetic epidemiology data for frequency of allele Δ32 CCR5 for Bosnian Croats and Bosnian Serbs.

Acknowledgements

ACKNOWLEDGMENTS

We are grateful to all DNA donors who made this study possible. This research was partially supported by the Medical Faculty University of Sarajevo and University Clinical Center Tuzla (Bosnia and Herzegovina) and Pomeranian Medical University, Szczecin (Poland).

DECLARATION OF INTEREST

The authors state no conflict of interests.

REFERENCES

  1. , (). Role of chemokines polymorphisms in diseases. Immunol Lett.
  2. , , , , , (). CCR5 gene polymorphism is a genetic risk factor for radiographic severity of rheumatoid arthritis. Tissue Antigens.
  3. , , , , , (). CCR5Δ32 Polymorphism Associated with a Slower Rate Disease Progression in a Cohort of RR-MS Sicilian Patients. Mult Scler Int 2011.
  4. , , , , , (). Genetic polymorphism of chemokine receptors CCR2 and CCR5 in Swedish cervical cancer patients. Anticancer Res.
  5. , (). The chemokine receptor, CCR5. Int J Biochem Cell Biol.
  6. (). Dancing to the tune of chemokines. Nat Immunol.
  7. , , , (). The role of the CCR5 Δ32 polymorphism in abdominal aortic aneurysms. Int J Immunogenet.
  8. , , , , , (). International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev.
  9. , , , , , (). The deltaccr5 mutation conferring protection against HIV-1 in Caucasian populationshas a single and recent origin in Northeastern Europe. Hum Mol Genet.
  10. , , , , , (). 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.
  11. , , , , , (). Reduced cell surface expression of CCR5 in CCR5Delta 32 heterozygotes is mediated by gene dosage, rather than by receptor sequestration. J Biol Chem.
  12. , , , , , (). The genetic variation of CCR5, CXCR4 and SDF-1 in three Chinese ethnic populations. Infect Genet Evol.
  13. , , , , , , , , , (). CC chemokine receptor 5 polymorphism in Italian patients with giant cell arteritis. Mod Rheumatol.
  14. , (). Distribution of functional polymorphic variants of inflammation-related genes RANTES and CCR5 in long-lived individuals. Cytokine.
  15. , (). Role of chemokines polymorphisms in diseases. Immunol Lett.
  16. (). 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.
  17. , (). Biology of plaques: Evidence from Historical Populations.
  18. , , , , , (). Dating theorigin of the CCR5-Delta32 AIDS-resistance allele by the coalescence of haplotypes. Am J Hum Genet.
  19. , , , , (). Common CCR 5 polymorphism in stroke: the CCR 5 delta32 polymorphism differentiates cardioembolism from other aetiologies of ischaemic cerebrovascular diseases. Scand J Immunol.
  20. , , , , (). Interleukin-24, RANTES and CCR5 gene polymorphisms are not associated with chronic adult periodontitis. J Periodontal Res.
  21. , , , , , (). Chemokine receptor 5 and primary biliary cirrhosis: a two-centre genetic association study. Liver Int.
  22. , , (). Absence of the deltaccr5 mutation in indigenous populations of the Brazilian Amazon. Hum Genet.
  23. , (). Distribution of the HIV resistance CCR5-Delta32 allele among Egyptians and Syrians. Mutat Res.
  24. , , , , , (). Distribution of CCR5-{delta}32, CCR2-64I, and SDF1-3’A in Guangxi Zhuang population. J Int Assoc Physicians AIDS Care (Chic).
  25. , , , , , (). Analysis of the CC chemokine receptor 5 (CCR5) delta-32 polymorphism in inflammatory bowel disease. Hum Genet.
  26. , , , , , (). Determination of the CCR5Δ32 frequency in Emiratis and Tunisians and the screening of the CCR5 gene for novel alleles in Emiratis. Gene.
  27. , , , , , (). Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature.
  28. , , , , , , (). The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med.
  29. , , , , , (). Chemokine receptor CCR5 in interferon-treated multiple sclerosis. ActaNeurol Scand.
  30. , , , , , , (). CC chemokine receptor 5 and interleukin-1 receptor antagonist gene polymorphisms in patients with primary Sjögren's syndrome. Clin Exp Rheumatol.
  31. , , , , , (). The frequency of allele CCR5Δ32 in a Serbian population. J Med Biochem.
  32. , , , , (). frequency of CCR5 gene 32-basepair deletion in Croatian normal population. Croat Med J.
  33. , , , , , (). CC chemokine receptor 5 polymorphism in Italianpatients with Behcet's disease. Rheumatology (Oxford).
  34. , , , , , (). Historic, Demographic, and Genetic Evidence for Increased Population Frequencies of CCR5Δ32 Mutation in Croatian Island Isolates after Lethal 15th Century Epidemics. Croat Med J.
  35. , , , , , (). Genetic control of chemokines in severe human internal carotid artery stenosis. Cytokine.
  36. , , (). Historic exposure to plague and present-day frequency of CCR5del32 in two isolated island communities of Dalmatia, Croatia. Croat Med J.
  37. , , , , , (). Lack of association of human chemokine receptor gene polymorphisms CCR2-64I and CCR5 delta32 with autoimmune Addison's disease. Eur J Immunogenet.
  38. , , , , , (). CCR2-64I polymorphism and CCR5D32 deletion in patients with Alzheimer's disease. J Neurol Sci.
  39. , , , , , (). Role of the CCR5/32CCR5 polymorphism in biopsy-proven giant cell arteritis. Hum Immunol.
  40. , , , , , (). 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.
  41. , , , , , (). 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-1Infected Subjects. J Acquir Immune DeficSyndr.
  42. , , , , , (). Chemokines (RANTES and MCP-1) and chemokine-receptors (CCR2 and CCR5) gene polymorphisms in Alzheimer's and Parkinson's disease. NeurosciLett.
  43. , , , (). 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.
  44. , , , , , (). Polymorphisms in chemokine and receptor genes and gastric cancer risk and survival in a high risk Polish population. Scand J Gastroenterol.
  45. , , , , , (). Sequence variants of chemokine receptor genes and susceptibility to HIV-1 infection. J Appl Genet.
  46. , , , , , (). Female-specific association of C-C chemokine receptor 5 gene polymorphisms with Löfgren's syndrome. J Mol Med (Berl).
  47. , (). HIV-1 aprotecting CCR5-D32 allele in medieval Poland. Infect Genet Evol.
  48. , , , , , (). Risk of Diabetic Nephropathy in Type 1 Diabetes IsAssociated With Functional Polymorphisms in RANTES Receptor Gene (CCR5) - a Sex-Specific Effect. Diabetes.
  49. , , , , , (). CC chemokine receptor 5 D32 polymorphism in two independent cohorts of hepatitis C virus infected patients without hemophilia. J Mol Med (Berl).
  50. , , , , (). Prevalence of the chemokine receptor CCR5-Delta32 gene mutation in periodontal disease. ClinImmunol.
  51. , , , , (). Polymorphism of CC chemokine receptors CCR2 and CCR5 in Crohn's disease. ImmunolLett.
  52. , , (). Balanced polymorphism selected by genetic versus infectious human disease. Annu Rev Genomics Hum Genet.
  53. , , , , , (). CC Chemokine Receptor Gene Polymorphisms in Czech Patients with Pulmonary Sarcoidosis. ImmunolLett.
  54. , , , (). Prevalence of Alleles Associated with HIV Resistance in Russia. Genet Test.