Contribution for new genetic markers of rheumatoid arthritis activity and severity : sequencing of the tumor necrosis factor-alpha gene promoter

© 2007 Fonseca et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedThe objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-alpha) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-alpha gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-alpha promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.This work was supported by grant POCTI/SAU-ESP/59111/2004 from Fundação Ciência e Tecnologia.info:eu-repo/semantics/publishedVersio

Gene expression profiling and association studies implicate the neuregulin signaling pathway in Behçet's disease susceptibility

© Springer-Verlag Berlin Heidelberg 2013Behçet's disease (BD) is a complex disease with genetic and environmental risk factors implicated in its etiology; however, its pathophysiology is poorly understood. To decipher BD's genetic underpinnings, we combined gene expression profiling with pathway analysis and association studies. We compared the gene expression profiles in peripheral blood mononuclear cells (PBMCs) of 15 patients and 14 matched controls using Affymetrix microarrays and found that the neuregulin signaling pathway was over-represented among the differentially expressed genes. The Epiregulin (EREG), Amphiregulin (AREG), and Neuregulin-1 (NRG1) genes of this pathway stand out as they are also among the top differentially expressed genes. Twelve haplotype tagging SNPs at the EREG-AREG locus and 15 SNPs in NRG1 found associated in at least one published BD genome-wide association study were tested for association with BD in a dataset of 976 Iranian patients and 839 controls. We found a novel association with BD for the rs6845297 SNP located downstream of EREG, and replicated three associations at NRG1 (rs4489285, rs383632, and rs1462891). Multifactor dimensionality reduction analysis indicated the existence of epistatic interactions between EREG and NRG1 variants. EREG-AREG and NRG1, which are members of the epidermal growth factor (EGF) family, seem to modulate BD susceptibility through main effects and gene-gene interactions. These association findings support a role for the EGF/ErbB signaling pathway in BD pathogenesis that warrants further investigation and highlight the importance of combining genetic and genomic approaches to dissect the genetic architecture of complex diseases.This research was supported by the Research Committee of the Tehran University of Medical Sciences (grant 132/714), the Portuguese Fundação para a Ciência e a Tecnologia (grant PTDC/SAU-GMG/098937/2008, doctoral fellowship SFRH/BD/43895/2008 to JMX, and a Ciência contract to SAO), and the Portuguese Instituto do Emprego e Formação Profissional (fellowship to JMX, TK, BVF).info:eu-repo/semantics/publishedVersio

Trinta e dois anos do programa de melhoramento do feijoeiro comum em Minas Gerais Thirty two years of common bean breeding in Minas Gerais state

Conduziu-se este trabalho, com o objetivo de proceder à análise crítica do Programa de melhoramento genético do feijoeiro comum em Minas Gerais nos últimos 32 anos com ênfase nas implicações da interação linhagens x ambientes, além de avaliar se houve progresso genético. Para isso, foram utilizados dados de 169 experimentos conduzidos no período de 1974 a 2004 e que envolveram 16 locais e três safras. A média da cultivar Carioca, comum em todos os experimentos, foi utilizada como estimador do efeito ambiental e a média das cinco melhores linhagens sob avaliação de cada biênio, como efeito fenotípico. A diferença entre essas duas médias forneceu o desvio genético. O coeficiente de regressão linear entre desvio genético Y (variável dependente) e o biênio X (variável independente) forneceu a estimativa do progresso genético. As interações linhagens x safras e linhagens x anos foram, na maioria dos casos, significativas, contudo, suas contribuições para a variação total foram inferiores a de linhagens x locais. Desse modo, fica clara a necessidade de que os experimentos sejam conduzidos em um maior número de locais. O programa de melhoramento genético do feijoeiro da UFLA tem sido eficiente e tem obtido linhagens com menor risco de adoção.<br>The objective of the present work was to make critical analysis of the dry bean genetic breeding program in Minas Gerais in the last 32 years by lines x environments interactions and genetic progress evaluations. Data from 169 experiments conducted from 1974 to 2004 in 16 locations and three seasons per year were used. The average of the cultivar Carioca, test in all experiments, was used as indicator of environmental variation; and the average of the five best lines, under evaluation in each biennium, was used as indicator of phenotypic variation. The difference between these two averages was used as genetic deviation. Genetic progress was estimated by linear regression coefficient between genetic deviation Y (dependent variable) and biennium X (independent variable). The interactions among lines x seasons and lines x years were significant in most cases, however, their contributions to the total variation were inferior to the lines x locations. Thus, it was necessary to conduct experiments in a larger number of locations. The common bean breeding program at UFLA has been efficient and has selected lines with less risk for adoption for farmers

Estimated distribution of the Sharp/van der Heijde (SvdH) score according to the duration of the disease (DD)

<p><b>Copyright information:</b></p><p>Taken from "Contribution for new genetic markers of rheumatoid arthritis activity and severity: sequencing of the tumor necrosis factor-alpha gene promoter"</p><p>http://arthritis-research.com/content/9/2/R37</p><p>Arthritis Research & Therapy 2007;9(2):R37-R37.</p><p>Published online 4 Apr 2007</p><p>PMCID:PMC1906815.</p><p></p