Publications (7)20.73 Total impact
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Article: Associations of the IL2Rα, IL4Rα, IL10Rα, and IFNγR1 cytokine receptor genes with AIDS progression in a French AIDS cohort
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ABSTRACT: We have performed an extensive analysis of Th1/Th2 cytokine receptors IL2Rα, IL4Rα, IL10Rα, and IFNγR1 gene polymorphisms to evaluate their impact on AIDS progression. The coding regions and promoters of these genes were sequenced in the genetics of resistance to immunodeficiency virus cohort, composed of 327 HIV-1-positive patients with extreme progression phenotypes, slow and rapid progressors, and of 446 healthy control subjects, all of them of Caucasian descent. Overall, 104 single nucleotide polymorphisms and four insertions/deletions with a minor allelic frequency higher than 1% were identified, 21 of them being newly characterized. We observed weak associations for 13 polymorphisms of IL2Rα, IL4Rα, IL10Rα, and IFNγR1, and 11 haplotypes of IL2Rα, IL4Rα, and IFNγR1. However, we could not relate these positive signals to any relevant biological information on the gene function. To affirm these putative associations in AIDS, further confirmation on other AIDS cohorts will be needed. This complete catalog of polymorphisms in IL2Rα, IL4Rα, IL10Rα, and IFNγR1 cytokine receptor genes should also be useful for investigating associations in other immune-related diseases.Immunogenetics 04/2012; 58(2):89-98. · 2.93 Impact Factor -
Article: Identification of IL7RA risk alleles for rapid progression during HIV-1 infection: a comprehensive study in the GRIV cohort.
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ABSTRACT: Interleukin 7 (IL7) is a critical factor for lymphocyte homeostasis. A dysfunction of the IL7/IL7R pathway has previously been described in HIV-1 infection, and promising results were observed in recent analyses of IL7 for therapeutic use in HIV infected individuals. However, further investigations are still warranted to understand the possible roles of this cytokine. Here, we explored whether the IL7 and IL7RA genetic polymorphisms were associated with the progression of HIV infection. We extensively genotyped the IL7 and IL7RA genes in the GRIV (Genomics of Resistance to Immunodeficiency Virus) cohort, composed of patients with extreme progression profiles - long-term non (LTNP) and rapid (RP) progressors--, and in a healthy control group (CTR). Statistical case-control analyses were performed using the Fisher's exact test, comparing either LTNP vs CTR or RP vs CTR. Three IL7RA SNPs (single nucleotide polymorphisms--rs7701176, rs987106 and rs10491434), but no IL7 SNPs, were significantly associated with rapid disease progression (P < 0.01). In a multi-marker analysis focusing on functional variants, a strong association between an IL7RA haplotype and rapid progression was observed (P = 5.59 x 10(-3)). In summary, our comprehensive genetic study revealed three SNPs and a risk of haplotype associated with rapid progression to AIDS in the IL7RA gene. Interestingly, the haplotype is composed of SNPs previously identified in other inflammatory diseases (e.g., multiple sclerosis) by GWAS and by functional studies. Our results contribute to the growing understanding of the role of IL7/IL7R in HIV disease progression, and more widely, in CD4+ T cell homeostasis.Current HIV research 02/2012; 10(2):143-50. · 1.98 Impact Factor -
Article: Associations of the IL2Ralpha, IL4Ralpha, IL10Ralpha, and IFN (gamma) R1 cytokine receptor genes with AIDS progression in a French AIDS cohort.
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ABSTRACT: We have performed an extensive analysis of Th1/Th2 cytokine receptors IL2Ralpha, IL4Ralpha, IL10Ralpha, and IFNgammaR1 gene polymorphisms to evaluate their impact on AIDS progression. The coding regions and promoters of these genes were sequenced in the genetics of resistance to immunodeficiency virus cohort, composed of 327 HIV-1-positive patients with extreme progression phenotypes, slow and rapid progressors, and of 446 healthy control subjects, all of them of Caucasian descent. Overall, 104 single nucleotide polymorphisms and four insertions/deletions with a minor allelic frequency higher than 1% were identified, 21 of them being newly characterized. We observed weak associations for 13 polymorphisms of IL2Ralpha, IL4Ralpha, IL10Ralpha, and IFNgammaR1, and 11 haplotypes of IL2Ralpha, IL4Ralpha, and IFNgammaR1. However, we could not relate these positive signals to any relevant biological information on the gene function. To affirm these putative associations in AIDS, further confirmation on other AIDS cohorts will be needed. This complete catalog of polymorphisms in IL2Ralpha, IL4Ralpha, IL10Ralpha, and IFNgammaR1 cytokine receptor genes should also be useful for investigating associations in other immune-related diseases.Immunogenetics 05/2006; 58(2-3):89-98. · 2.93 Impact Factor -
Article: Computation of haplotypes on SNPs subsets: advantage of the "global method".
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ABSTRACT: Genetic association studies aim at finding correlations between a disease state and genetic variations such as SNPs or combinations of SNPs, termed haplotypes. Some haplotypes have a particular biological meaning such as the ones derived from SNPs located in the promoters, or the ones derived from non synonymous SNPs. All these haplotypes are "subhaplotypes" because they refer only to a part of the SNPs found in the gene. Until now, subhaplotypes were directly computed from the very SNPs chosen to constitute them, without taking into account the rest of the information corresponding to the other SNPs located in the gene. In the present work, we describe an alternative approach, called the "global method", which takes into account all the SNPs known in the region and compare the efficacy of the two "direct" and "global" methods. We used empirical haplotypes data sets from the GH1 promoter and the APOE gene, and 10 simulated datasets, and randomly introduced in them missing information (from 0% up to 20%) to compare the 2 methods. For each method, we used the PHASE haplotyping software since it was described to be the best. We showed that the use of the "global method" for subhaplotyping leads always to a better error rate than the classical direct haplotyping. The advantage provided by this alternative method increases with the percentage of missing genotyping data (diminution of the average error rate from 25% to less than 10%). We applied the global method software on the GRIV cohort for AIDS genetic associations and some associations previously identified through direct subhaplotyping were found to be erroneous. The global method for subhaplotyping can reduce, sometimes dramatically, the error rate on patient resolutions and haplotypes frequencies. One should thus use this method in order to minimise the risk of a false interpretation in genetic studies involving subhaplotypes. In practice the global method is always more efficient than the direct method, but a combination method taking into account the level of missing information in each subject appears to be even more interesting when the level of missing information becomes larger (>10%).BMC Genetics 01/2006; 7:50. · 2.47 Impact Factor -
Article: Genomic approach of AIDS pathogenesis: exhaustive genotyping of the TNFR1 gene in a French AIDS cohort.
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ABSTRACT: Large-scale genomic studies in cohorts have been made possible for the last few years thanks to the progress of molecular biology and bioinformatics. This systematic approach allows a better understanding of the molecular mechanisms of disease development and as a consequence can contribute to the rational design of new diagnostic and therapeutic tools. We present here the exhaustive genotyping of a candidate gene, tumor necrosis factor receptor 1 (TNFR1), in the genetic of resistance to immunodeficiency virus (GRIV) AIDS cohort. This gene was chosen because it is likely to be involved in the apoptosis pathways of CD4+ and CD8+ T-cells during human immunodeficiency virus 1 (HIV-1) infection. Seven frequent polymorphisms were characterized in 319 HIV-1 seropositive patients from the GRIV cohort with extreme disease progression phenotypes, slow progression or rapid progression, and in 427 healthy controls. The TNFR1 gene locus does not appear to be part of any haploblock and contains only a small haploblock of two successive SNPs. One promoter SNP (TNFR1_17444594, position -581) and one intronic SNP (TNFR1_27223241, position +11511) gave weak positive signals of association (resp. P=0.03 and P=0.04) as well as two haplotypes. To our knowledge, this is the first genetic association study dealing with the TNFR1 gene in AIDS and the putative associations identified will need to be validated through other AIDS cohort analyses or by further biological experimentation.Biomedecine [?] Pharmacotherapy 10/2005; 59(8):474-80. · 2.00 Impact Factor -
Article: Exhaustive genotyping of the CEM15 (APOBEC3G) gene and absence of association with AIDS progression in a French cohort.
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ABSTRACT: CEM15 (or APOBEC3G) has recently been identified as an inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in vitro. To evaluate the impact of its genetic variations on the progression of acquired immunodeficiency syndrome (AIDS), we have performed an extensive genetic analysis of CEM15. We have sequenced CEM15 in a cohort of 327 HIV-1-seropositive patients with extreme disease progression phenotypes--either slow progression or rapid progression--and in 446 healthy control subjects, all of white descent. We have identified 29 polymorphisms with allele frequencies >1%, 14 of which were newly characterized. There were no significant associations between the polymorphisms or haplotypes of CEM15 and a disease progression phenotype in our cohort.The Journal of Infectious Diseases 02/2005; 191(2):159-63. · 6.41 Impact Factor -
Article: Analysis of IGG and IGG4 in HIV-1 seropositive patients and correlation with biological and genetic markers.
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ABSTRACT: We have compared the levels of immunoglobulins G (IgG) and G4 (IgG4) in extreme seropositive patients from the GRIV cohort consisting of 168 patients with slow progression (SP) and 60 with rapid progression (RP) as well as in 173 healthy controls. IgG levels were significantly higher in SP patients than in RP patients (P = 0.008), both higher than in seronegative individuals. IgG4 levels were significantly lower in SP patients than in RP patients (P = 0.001), both lower than in seronegative individuals. We tried to correlate these levels with biological parameters (CD4(+) and CD8(+) cells, total lymphocytes, white blood cell counts, percentage of CD4(+) cells, and viral load) as well as with genetic markers from Th1/Th2 cytokines (IL2, IL4, IL6, IL10, IL13, and IFNgamma). IgG levels were correlated with the percentage of CD4(+) cells in SP while IgG4 levels were correlated with CD8(+) cell count in SP and with percentage of CD4(+) cells in RP patients. Among the parameters measured in SP patients at the time of inclusion in the study, the best predictor of progression towards AIDS was the viral load, the best predictor for stability was CD4(+) cell count, but overall, the best predictor for SP evolution (stability vs. progression) appeared to be the percentage of CD4(+) cells. Interestingly, correlations between the levels of IgG or IgG4 and the cytokine gene polymorphisms were found, notably in the IL10 gene.Biomedecine [?] Pharmacotherapy 59(1-2):38-46. · 2.00 Impact Factor
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2012
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Conservatoire National des Arts et Métiers
Paris, Ile-de-France, France
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