IL28B Gene Polymorphism SNP rs8099917 Genotype GG Is Associated with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in HTLV-1 Carriers

The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP. The study included 229 subjects, classified...

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Published inPLoS neglected tropical diseases Vol. 8; no. 9; p. e3199
Main Authors Assone, Tatiane, Souza, Fernando Vieira de, Gaester, Karen Oliveira, Fonseca, Luiz Augusto Marcondes, Luiz, Olinda do Carmo, Malta, Fernanda, Pinho, João Renato Rebello, Gonçalves, Fernanda de Toledo, Duarte, Alberto Jose da Silva, de Oliveira, Augusto Cesar Penalva, Casseb, Jorge
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 01.09.2014
Public Library of Science (PLoS)
Subjects
Adult
Aged
Biology and Life Sciences
Cytokines
Deoxyribonucleic acid
Development and progression
Disease
DNA
Female
Genes
Genetic aspects
Genotype
Genotype & phenotype
HTLV-I Infections - complications
HTLV-I Infections - virology
Human T-lymphotropic virus 1
Humans
Infections
Interferons
Interleukins
Interleukins - genetics
Male
Medicine and Health Sciences
Middle Aged
Paraparesis, Tropical spastic
Paraparesis, Tropical Spastic - genetics
Pathogenesis
Polymerase Chain Reaction
Polymorphism, Single Nucleotide - genetics
Properties
Proviruses - genetics
Real-Time Polymerase Chain Reaction
Single nucleotide polymorphisms
Viral infections
Viral Load
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Abstract The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP. The study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System. A multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95% = 0.96-4.27) and in rs8099917 genotype GG (OR = 7.61; IC95%  = 1.82-31.72). Subjects with SNP rs8099917 genotype GG and rs12979618 genotype CT may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of such finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.
AbstractList The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP. The study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System. A multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95% = 0.96-4.27) and in rs8099917 genotype GG (OR = 7.61; IC95%  = 1.82-31.72). Subjects with SNP rs8099917 genotype GG and rs12979618 genotype CT may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of such finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.
New evidence has shown that the pathogenic mechanism of disease-associated HTLV-1 infection is an impairment of the immunity. More recently, it has been demonstrated that IL28B polymorphisms are more likely to occur among HTLV-1 infected subjects and are associated with higher proviral loads in HTLV-1 carriers. Based on anti-HCV properties exhibited by IL28B, we examined the possibility of an association between IL28B polymorphisms (rs8099917 and rs12979860 SNPs) and HAM/TSP occurrence in a large cohort of HTLV-1-infected subjects in Sao Paulo city, Brazil. This study included 229 HTLV-1-infected subjects classified according to their neurological status in two groups (asymptomatic vs HAM/TSP cases), and observed that persons with SNP rs8099917 genotype GG and rs12979860 genotype CT may present a distinct immune response against HTLV-1 infection. Thus, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for HAM/TSP development.
BACKGROUND:The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP. METHODS:The study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System. RESULTS:A multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95% = 0.96-4.27) and in rs8099917 genotype GG (OR = 7.61; IC95%  = 1.82-31.72). CONCLUSION:Subjects with SNP rs8099917 genotype GG and rs12979618 genotype CT may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of such finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.
The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP.BACKGROUNDThe polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP.The study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System.METHODSThe study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System.A multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95% = 0.96-4.27) and in rs8099917 genotype GG (OR = 7.61; IC95%  = 1.82-31.72).RESULTSA multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95% = 0.96-4.27) and in rs8099917 genotype GG (OR = 7.61; IC95%  = 1.82-31.72).Subjects with SNP rs8099917 genotype GG and rs12979618 genotype CT may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of such finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.CONCLUSIONSubjects with SNP rs8099917 genotype GG and rs12979618 genotype CT may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of such finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.
  Background The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP. Methods The study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System. Results A multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95% = 0.96-4.27) and in rs8099917 genotype GG (OR = 7.61; IC95% = 1.82-31.72). Conclusion Subjects with SNP rs8099917 genotype GG and rs12979618 genotype CT may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of such finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.
Audience Academic
Author Souza, Fernando Vieira de
Malta, Fernanda
Pinho, João Renato Rebello
Casseb, Jorge
Gonçalves, Fernanda de Toledo
Fonseca, Luiz Augusto Marcondes
Duarte, Alberto Jose da Silva
Assone, Tatiane
Luiz, Olinda do Carmo
Gaester, Karen Oliveira
de Oliveira, Augusto Cesar Penalva
AuthorAffiliation Hospital Universitário, Brazil
2 Instituto de Medicina Tropical de São Paulo, São Paulo, São Paulo, Brazil
1 Laboratório de Dermatologia e Imunodeficiências, Departamento de Dermatologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil
3 Instituto de Doenças Infecciosas “Emilio Ribas” (IIER) de São Paulo, São Paulo, São Paulo, Brazil
5 Laboratório de Imuno-hematologia e Hematologia Forense – LIM40, Departamento de Medicina Legal, Ética Médica, Medicina Social e do Trabalho, Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, São Paulo, Brazil
4 Departamento de Medicina Preventiva, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil
AuthorAffiliation_xml – name: 1 Laboratório de Dermatologia e Imunodeficiências, Departamento de Dermatologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil
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ContentType Journal Article
Copyright COPYRIGHT 2014 Public Library of Science
2014 Assone et al 2014 Assone et al
2014 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Assone T, Souza FVd, Gaester KO, Fonseca LAM, Luiz OdC, Malta F, et al. (2014) IL28B Gene Polymorphism SNP rs8099917 Genotype GG Is Associated with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in HTLV-1 Carriers. PLoS Negl Trop Dis 8(9): e3199. doi:10.1371/journal.pntd.0003199
Copyright_xml – notice: COPYRIGHT 2014 Public Library of Science
– notice: 2014 Assone et al 2014 Assone et al
– notice: 2014 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Assone T, Souza FVd, Gaester KO, Fonseca LAM, Luiz OdC, Malta F, et al. (2014) IL28B Gene Polymorphism SNP rs8099917 Genotype GG Is Associated with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in HTLV-1 Carriers. PLoS Negl Trop Dis 8(9): e3199. doi:10.1371/journal.pntd.0003199
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Conceived and designed the experiments: TA JC FVdS. Performed the experiments: TA KOG FM. Analyzed the data: LAMF OdCL FdTG. Contributed reagents/materials/analysis tools: TA FVdS JC JRRP. Contributed to the writing of the manuscript: TA JC ACPdO LAMF AJdSD.
The authors have declared that no competing interests exist.
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Snippet The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate...
Background: The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was...
New evidence has shown that the pathogenic mechanism of disease-associated HTLV-1 infection is an impairment of the immunity. More recently, it has been...
BACKGROUND:The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was...
  Background The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was...
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SubjectTerms Adult
Aged
Biology and Life Sciences
Cytokines
Deoxyribonucleic acid
Development and progression
Disease
DNA
Female
Genes
Genetic aspects
Genotype
Genotype & phenotype
HTLV-I Infections - complications
HTLV-I Infections - virology
Human T-lymphotropic virus 1
Humans
Infections
Interferons
Interleukins
Interleukins - genetics
Male
Medicine and Health Sciences
Middle Aged
Paraparesis, Tropical spastic
Paraparesis, Tropical Spastic - genetics
Pathogenesis
Polymerase Chain Reaction
Polymorphism, Single Nucleotide - genetics
Properties
Proviruses - genetics
Real-Time Polymerase Chain Reaction
Single nucleotide polymorphisms
Viral infections
Viral Load
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Title IL28B Gene Polymorphism SNP rs8099917 Genotype GG Is Associated with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in HTLV-1 Carriers
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http://dx.doi.org/10.1371/journal.pntd.0003199
Volume 8
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