Abstract
Frequencies of genetic polymorphisms of the three most frequent HIV-1 resistance-conferring alleles playing an important role in HIV-1 pathogenesis were analysed in Vlach Gypsy populations living in Hungary, as the largest minority. Mutations in the encoding genes, such as CCR5-∆32, CCR2-64I and SDF1-3’A are shown to result in protective effects against HIV-1 infection and disease progression. 560 samples collected from Vlach Gypsy individuals living in 6 North-East Hungarian settlements were genotyped by PCR-RFLP method. Overall allele frequencies of CCR5-∆32, CCR2-64I and SDF1-3’A were found as 0.122, 0.186 and 0.115 respectively. All the observed genotype frequencies were in accordance with Hardy-Weinberg equilibrium . In regions, however, Vlach Gypsies live in majority and in ethnically homogenous communities, a higher CCR5-∆32 mutations were found, with allele frequencies of 0.148 and 0.140 respectively, which are remarkably higher than those in general Hungarian people, and ten times higher than in regions of North-Western India from where present day Hungarian Gypsies originated in the Middle Ages. In the background of this higher CCR5-∆32 allele frequency in the population analysed in our study a genetic founder effect could be assumed. Allele frequency of CCR2-64I was found to be among the highest in Europe. SDF1-3’A allele frequency in Vlach Gypsies was significantly lower than in ethnic Hungarians. 63% of the total 560 individuals tested carried at least one of the mutations studied. These results could partially explain the low incidence of HIV/AIDS among Vlach Gypsies in Hungary.
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References
Kalaydjieva L, Lochmüller H, Tounev I et al (2005) Neuromuscular disorders in the Roma (Gypsy) population. Neuromuscul Disord 15:65–71
Almos PZ, Horvath S, Czibula A et al (2008) H1 tau haplotype-related genomic variations at 17q21.3 as an Asian heritage of the European Gypsy population. Heredity 101:416–419
Trkola A (2004) HIV-host interactions: vital to the virus and key to its inhibition. Curr Opin Microbiol 7:555–559
Reiche EM, Bonametti AM, Voltarelli JC et al (2007) Genetic polymorphisms in the chemokine and chemokine receptors: impact on clinical course and therapy of the human immunodeficiency virus type 1 infection (HIV-1). Curr Med Chem 14:1325–1334
de Silva E, Stumpf MP (2004) HIV and the CCR5-Delta32 resistance allele. FEMS Microbiol Lett 241:1–12
Jin Q, Agrawal L, Meyer L et al (2008) CCR5{delta}32 59537-G/A promoter polymorphism is associated with low translational efficiency and the loss of the CCR5{Delta}32 protective effects. J Virol 82:2418–2426
Kaslow RA, Dorak T, Tang JJ (2005) Influence of host genetic variation on susceptibility to HIV type 1 infection. J Infect Dis 191:S68–S77
Su B, Sun G, Lu D et al (2000) Distribution of three HIV-1 resistance-conferring polymorphisms (SDF1-3’A, CCR2-641, and CCR5-delta32) in global populations. Eur J Hum Genet 8:975–979
Lucotte G (2002) Frequencies of 32 base pair deletion of the (delta 32) allele of the CCR5 HIV-1 coreceptor gene in Caucasians: a comparative analysis. Infect Genet Evol 1:201–205
Winkler C, An P, O'Brien SJ (2004) Patterns of ethnic diversity among the genes that influence AIDS. Hum Mol Genet 13:R9–R19
Smith MW, Dean M, Carrington M et al (1997) Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE study. Science 277:959–965
O'Brien SJ, Nelson GW (2004) Human genes that limit AIDS. Nat Genet 36:565–574
Gharagozloo M, Doroudchi M, Farjadian S et al (2005) The frequency of CCR5Delta32 and CCR2-64I in southern Iranian normal population. Immunol Lett 96:277–281
Winkler C, Modi W, Smith MW et al (1998) Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC). Science 279:389–393
Kemény B, Nagy K, Horváth A (2000) CCR5 and SDF1 gene polymorphism in HIV-infected and healthy individuals in Hungary. Hung Venerol Arch 4:89–92
Magierowska M, Theodorou I, Debré P et al (1999) Combined genotypes of CCR5, CCR2, SDF1, and HLA genes can predict the long-term nonprogressor status in human immunodeficiency virus-1-infected individuals. Blood 93:936–941
Apostolakis S, Baritaki S, Krambovitis E et al (2005) Distribution of HIV/AIDS protective SDF1, CCR5 and CCR2 gene variants within Cretan population. J Clin Virol 34:310–314
Choi BS, Choi JH, Kim SS et al (2007) CCR2b-64I allelic polymorphisms in advanced HIV-infected Koreans accelerate disease progression. AIDS Res Hum Retroviruses 23:805–811
Szalai C, Czinner A, Császár A et al (1998) Frequency of the HIV-1 resistance CCR5 deletion allele in Hungarian newborns. Eur J Pediatr 157:782
Husain S, Goila R, Shahi S et al (1998) First report of a healthy Indian heterozygous for delta 32 mutant of HIV-1 co-receptor-CCR5 gene. Gene 207:141–147
Majumder PP, Dey B (2001) Absence of the HIV-1 protective delta ccr5 allele in most ethnic populations of India. Eur J Hum Genet 9:794–796
Suresh P, Wanchu A, Sachdeva RK et al (2006) Gene polymorphisms in CCR5, CCR2, CX3CR1, SDF-1 and RANTES in exposed but uninfected partners of HIV-1 infected individuals in North India. J Clin Immunol 26:476–484
Verma R, Gupta RB, Singh K et al (2007) Distribution of CCR5delta32, CCR2-64I and SDF1-3’A and plasma levels of SDF-1 in HIV-1 seronegative North Indians. J Clin Virol 38:198–203
Kaur G, Singh P, Rapthap CC et al (2007) Polymorphism in the CCR5 gene promoter and HIV-1 infection in North Indians. Hum Immunol 68:454–461
Sharda S, Gilmour A, Harris V et al (2008) Chemokin receptor 5 (CCR5) deletion polymorphism in North Indian patients with coronary artery disease. Int J Cardiol 124:254–258
Aranka L, Peter M, Jeno K et al (2009) Genetically determined neuromuscular disorders of some Roma families living in Hungary. Ideggyogy Sz 62:41–47
Herczegfalvi A, Pikó H, Karcagi V (2008) Screening for hereditary neuromuscular disorders with molecular genetics methods in the Roma population of Hungary. Igeggyogy Sz 61:426–430
Szalai C, Császár A, Czinner A et al (1998) High frequency of the CCR5 deletion allele in gypsies living in Hungary. Immunol Lett 63:57–58
Szalai C, Császár A, Czinner A et al (1999) Chemokine receptor CCR2 and CCR5 polymorphisms in children with insulin-dependent diabetes mellitus. Pediatr Res 46:82–84
Ramana GV, Vasanthi A, Khaja M et al (2001) Distribution of HIV-1 resistance-conferring polymorphic alleles SDF-1-3’A, CCR2-64I and CCR5-Delta32 in diverse populations of Andhra Pradesh, South India. J Genet 80:37–40
Acknowledgements
We thank Prof. Bela Melegh and the Department of Medical Genetics and Child Development, University of Pécs for the DNA samples originated from Borsod. We also thank the expert work of Béla Kemény at the initial phase of the project, and Mónika Kapás for technical support. This research was supported by the Doctoral School of Semmelweis University and partly by OTKA 048917 Research Grant. The research was permitted by the Ethics Committee of Hungarian Council of Medical Sciences (TUKEB: 78/2000).
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Juhász, E., Béres, J., Kanizsai, S. et al. The Consequence of a Founder Effect: CCR5-∆32, CCR2-64I and SDF1-3’A Polymorphism in Vlach Gypsy Population in Hungary. Pathol. Oncol. Res. 18, 177–182 (2012). https://doi.org/10.1007/s12253-011-9425-4
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DOI: https://doi.org/10.1007/s12253-011-9425-4