Three allele combinations associated with Multiple Sclerosis

Фаворова, О. О.; Favorov, Alexander V.; Бойко, А. Н.; Andreewski, T. V.; Судомоина, М. А.; Alekseenkov, A. D.; Кулакова, О. Г.; Gusev, E I; Parmigiani, Giovanni; Ochs, Michael F.

doi:10.1186/1471-2350-7-63

Cited by 22 publications

(20 citation statements)

References 40 publications

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“…This requirement was thoroughly satisfied in our study for the genes from the first group. The MS association with DRB1 *15 HLA class II allele in Russians, which was revealed by TDT and AFBAC, had been shown earlier in population-based studies [36, 37]. On the other hand, we observed no MS association with alleles of the CTLA4, TGFB1, and CCR5 genes neither while carrying out the family-based analysis in this study nor while carrying out the case-control analysis on independent groups of unrelated individuals [37–39].…”

Section: Resultssupporting

confidence: 57%

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Family Analysis of Linkage and Association of HLA-DRB1, CTLA4, TGFB1, IL4, CCR5, RANTES, MMP9 and TIMP1 Gene Polymorphisms with Multiple Sclerosis

et al. 2011

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Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Proteins of the immune system, as well as proteins that are involved in the infiltration of activated immune cells in the CNS, play an important role in the pathogenesis of MS. We investigated the association and linkage with MS of the following immune-system genes polymorphisms: HLA-DRB1,CTLA4,TGFB1,IL4,CCR5 andRANTES, as well as of the matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1) genes polymorphisms. For this purpose we used the transmission disequilibrium test (TDT). The group investigated was comprised of 100 nuclear families of Russian ethnicity, each consisting of an affected offspring and his nonaffected parents. It was found that HLA-DRB1*15alleleandMMP9*-1562C allele were transmitted from healthy heterozygous parents to affected children more frequently than alternative alleles (p = 0.02 andp = 0.04, respectively). Another family-based method, AFBAC (affected family-based control), showed MS association with HLA-DRB1*15, but not with theMMP9*-1562C allele.

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Section: Resultssupporting

confidence: 57%

“…Indeed, the alleles CTLA4* 49G, TGFB1* (–509)С, and CCR5 *d are the parts of MS-predisposing bi- and tri-allelic combinations with alleles of other genes found using the APSampler algorithm [37]. Combinations of alleles including the CTLA4 and TGFB1 genes that are associated with MS were detected in other studies [2].…”

Section: Resultsmentioning

confidence: 89%

Family Analysis of Linkage and Association of HLA-DRB1, CTLA4, TGFB1, IL4, CCR5, RANTES, MMP9 and TIMP1 Gene Polymorphisms with Multiple Sclerosis

et al. 2011

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“…1 ) in the Russian population was previously demonstrated without the use of the APSampler algorithm and reproduced in an independent sample using the APSampler algorithm [68]. The replication of the data pertaining to the association of these genetic factors with the development of MS complies with the criteria widely accepted across the world’s scientific community for validation of the results and attests to the software’s efficiency.…”

Section: Studies Performed Using Apsamplersupporting

confidence: 52%

A Polygenic Approach to the Study of Polygenic Diseases

2012

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Polygenic diseases are caused by the joint contribution of a number of independently acting or interacting polymorphic genes; the individual contribution of each gene may be small or even unnoticeable. The carriage of certain combinations of genes can determine the occurrence of clinically heterogeneous forms of the disease and treatment efficacy. This review describes the approaches used in a polygenic analysis of data in medical genomics, in particular, pharmacogenomics, aimed at identifying the cumulative effect of genes. This effect may result from the summation of gains of different genes or be caused by the epistatic interaction between the genes. Both cases are undoubtedly of great interest in investigating the nature of polygenic diseases. The means that allow one to discriminate between these two possibilities are discussed. The methods for searching for combinations of alleles of different genes associated with the polygenic phenotypic traits of the disease, as well as the methods for presenting and validating the results, are described and compared. An attempt is made to evaluate the applicability of the existing methods to an epistasis analysis. The results obtained by the authors using the APSampler software are described and summarized.

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“…For example, associations of CCR5 Δ32 (Favorova et al 2002) and of VNTR polymorphism in MBP (Guerini et al 2003) were found only in DR-stratified individuals. This strategy of searching for combinations resulted in creation of the APSampler algorithm (Favorov et al 2005) that was successfully applied for MS cohorts and allowed finding the two three-allelic combinations associated with MS, both including HLA-DRB1 alleles (Favorova et al 2006).…”

Section: Introductionmentioning

confidence: 99%

A review of genome-wide association studies for multiple sclerosis: classical and hypothesis-driven approaches

et al. 2015

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Multiple sclerosis (MS) is a common complex neurodegenerative disease of the central nervous system. It develops with autoimmune inflammation and demyelination. Genome-wide association studies (GWASs) serve as a powerful tool for investigating the genetic architecture of MS and are generally used to identify the genetic factors of disease susceptibility, clinical phenotypes, and treatment response. This review considers the main achievements and challenges of using GWAS to identify the genes involved in MS. It also describes hypothesis-driven studies with extensive genome coverage of the selected regions, complementary to GWASs. To date, over 100 MS risk loci have been identified by the combination of both approaches; 40 of them were found in at least two GWASs and meet genome-wide significance threshold (p ≤ 5 × 10(-8)) in at least one GWAS, whereas the threshold for the rest of GWASs was set in our review at p < 1 × 10(-5). Yet, MS risk loci identified to date explain only a part of the total heritability, and the reasons of "missing heritability" are discussed. The functions of MS-associated genes are described briefly; the majority of them encode immune-response proteins involved in the main stages of MS pathogenesis.

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Three allele combinations associated with Multiple Sclerosis

Cited by 22 publications

References 40 publications

Family Analysis of Linkage and Association of HLA-DRB1, CTLA4, TGFB1, IL4, CCR5, RANTES, MMP9 and TIMP1 Gene Polymorphisms with Multiple Sclerosis

Family Analysis of Linkage and Association of HLA-DRB1, CTLA4, TGFB1, IL4, CCR5, RANTES, MMP9 and TIMP1 Gene Polymorphisms with Multiple Sclerosis

A Polygenic Approach to the Study of Polygenic Diseases

A review of genome-wide association studies for multiple sclerosis: classical and hypothesis-driven approaches

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