Distribution of HIV/AIDS protective SDF1, CCR5 and CCR2 gene variants within Cretan population.
ABSTRACT An interesting finding in the epidemiology of human immunodeficiency virus (HIV) infection is that certain mutations in genes coding for chemokine receptors and their ligands may confer resistance to HIV-1 infection and/or AIDS progression. The mutations most frequently studied are the CCR5-delta32, CCR2-64I and SDF1-3'A. We examined the frequency of the above polymorphisms within the Cretan population, evaluating their contribution to a protective genetic background against HIV infection and progression. Two hundred blood samples were recruited at random among prospective blood donors from Crete. Genotyping was initially performed by polymerase chain reaction (PCR) analysis. CCR2 and SDF-1 PCR-amplified genomic regions were further subjected to restriction fragment length polymorphism (RFLP) analysis for genotype determination. The CCR5-delta32 allele frequency among our study group was 3.25%, although no respective homozygous samples were detected. The screening for the CCR2-64I polymorphism yielded 39 heterozygous (19.5%) and 4 homozygous (2%) subjects, revealing a CCR2-64I allele frequency of 11.75%. Among our 200 PCR-RFLP analysed samples, 73 (36.5%) were found heterozygous and 23 (11.5%) homozygous for the SDF1-3'A mutant variant. The allele frequency of the above polymorphism reached 29.75%. The frequency of the CCR5-delta32 allele among our study population seems to be remarkably lower compared to previously reported frequencies in other Caucasian groups. However, the SDF1-3'A allele frequency shows significantly higher distribution profiles within our study group compared to those observed in other Caucasian-European populations. The indicated difference could be attributed to the increased homogeneity of our population, which is well balanced and dispersed over a small geographical area. Since this polymorphism is related with delayed progression from HIV infection to AIDS, it could be used for prognostic genotyping in HIV infected Cretan individuals.
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ABSTRACT: C-C chemokine receptor type 5 (CCR5) is known for its role as a co-receptor for HIV-1 infection. Some individuals possess a 32 bp deletion, known as Delta-32 allele which has been reported to confer resistance to HIV-1 infection. In order to estimate the distribution of Delta-32 allele of CCR5 gene, 1034 mestizo individuals from the Northwest of Mexico, including 385 HIV-1-infected individuals, 472 healthy controls and 177 uninfected female sex workers; were examined by allele-specific PCR. There was no statistically significant difference in the frequency of Delta-32 allele between HIV-1 positive and healthy individuals (OR= 1.1, p= 0.6). However, we found a significantly reduced prevalence of CCR5 Delta-32 heterozygous genotype in female patients (OR= 0.084, 95% CI= 0.011 - 0.630, p= 0.002), as well as in allele frequency, compared to male patients. Furthermore, we observed an inverse relationship between allele frequency and the risk of HIV-1 transmission and AIDS progression among female healthy controls, sex workers and HIV-1 infected groups. Our findings support previous data showing Delta-32 as a genetic protective factor against HIV-1 infection in Mexican women, as well as in women from other populations.Current HIV research 03/2014; DOI:10.2174/1570162X11666140101120225 · 2.14 Impact Factor
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ABSTRACT: We studied the possible effects of the expansion of ancient Mediterranean civilizations during the five centuries before and after Christ on the European distribution of the mutant allele for the chemokine receptor gene CCR5 which has a 32-bp deletion (CCR5-Delta32). There is a strong evidence for the unitary origin of the CCR5-Delta32 mutation, this it is found principally in Europe and Western Asia, with generally a north-south downhill cline frequency. Homozygous carriers of this mutation show a resistance to HIV-1 infection and a slower progression towards AIDS. However, HIV has clearly emerged too recently to have been the selective force on CCR5. Our analyses showed strong negative correlations in Europe between the allele frequency and two historical parameters, i.e. the first colonization dates by the great ancient Mediterranean civilizations, and the distances from the Northern frontiers of the Roman Empire in its greatest expansion. Moreover, other studies have shown that the deletion frequencies in both German Bronze Age and Swedish Neolithic populations were similar to those found in the corresponding modern populations, and this deletion has been found in ancient DNA of around 7000 years ago, suggesting that in the past, the deletion frequency could have been relatively high in European populations. In addition, in West Nile virus pathogenesis, CCR5 plays an antimicrobial role showing that host genetic factors are highly pathogen-specific. Our results added to all these previous data suggest that the actual European allele frequency distribution might not be due to genes spreading, but to a negative selection resulting in the spread of pathogens principally during Roman expansion. Indeed, as gene flows from colonizers to European native populations were extremely low, the mutational changes might be associated with vulnerability to imported infections. To date, the nature of the parasites remains unknown; however, zoonoses could be incriminated.Infection Genetics and Evolution 09/2008; 8(6):864-74. DOI:10.1016/j.meegid.2008.08.007 · 3.26 Impact Factor
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ABSTRACT: Atherosclerosis, the underlying disorder of coronary artery disease (CAD), is an inflammatory process involving multiple molecular pathways. Chemokine-mediated mechanisms are potent regulators of atherosclerosis. Genetic variations that alter such signaling pathways could affect susceptibility to CAD. We investigated the effect of 5 common variations of chemokine and chemokine receptor genes (SDF1-3'A, CCR5-delta32, CCR2-64I, CX3CR1-V249I and CX3CR1-T280M) on predisposition to CAD. The hypothesis was tested by screening the prevalence of the above polymorphisms in 210 angiographically diagnosed CAD patients (152 with history of acute coronary syndromes, 58 with stable disease) in comparison to 165 selected controls with negative coronary angiography. Genotyping was performed by PCR/RFLP analysis. There were no significant differences among cases and controls concerning allelic and genotypic frequencies of SDF1-3'A, CCR5-delta32, CCR2-64I and CX3CR1-V249I variations. A borderline higher allelic frequency of the M280 variant was observed in controls compared to CAD group (adjusted OR=0.65, 95% CI: 0.35-0.99, p=0.05). Subjects carrying at least one copy of the M280 allele were significantly more common in the control group, suggesting an atheroprotective effect of this variant (adjusted OR=0.58, 95% CI: 0.35-0.97, p=0.04). The study confers additional data in the field of genetic predisposition to CAD: it confirms the atheroprotective effect of the M280 variant in a completely different population and supports the role of the fractalkine-CX3CR1 pathway in atherosclerosis.Thrombosis Research 02/2007; 119(1):63-71. DOI:10.1016/j.thromres.2005.12.016 · 2.43 Impact Factor