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1.
BMJ ; 367: l5654, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619437

RESUMO

OBJECTIVE: To assess the efficacy of three months of antibiotic treatment compared with placebo in patients with chronic low back pain, previous disc herniation, and vertebral endplate changes (Modic changes). DESIGN: Double blind, parallel group, placebo controlled, multicentre trial. SETTING: Hospital outpatient clinics at six hospitals in Norway. PARTICIPANTS: 180 patients with chronic low back pain, previous disc herniation, and type 1 (n=118) or type 2 (n=62) Modic changes enrolled from June 2015 to September 2017. INTERVENTIONS: Patients were randomised to three months of oral treatment with either 750 mg amoxicillin or placebo three times daily. The allocation sequence was concealed by using a computer generated number on the prescription. MAIN OUTCOME MEASURES: The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (range 0-24) at one year follow-up in the intention to treat population. The minimal clinically important between group difference in mean RMDQ score was predefined as 4. RESULTS: In the primary analysis of the total cohort at one year, the difference in the mean RMDQ score between the amoxicillin group and the placebo group was -1.6 (95% confidence interval -3.1 to 0.0, P=0.04). In the secondary analysis, the difference in the mean RMDQ score between the groups was -2.3 (-4.2 to-0.4, P=0.02) for patients with type 1 Modic changes and -0.1 (-2.7 to 2.6, P=0.95) for patients with type 2 Modic changes. Fifty patients (56%) in the amoxicillin group experienced at least one drug related adverse event compared with 31 (34%) in the placebo group. CONCLUSIONS: In this study on patients with chronic low back pain and Modic changes at the level of a previous disc herniation, three months of treatment with amoxicillin did not provide a clinically important benefit compared with placebo. Secondary analyses and sensitivity analyses supported this finding. Therefore, our results do not support the use of antibiotic treatment for chronic low back pain and Modic changes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02323412.


Assuntos
Amoxicilina , Degeneração do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/complicações , Dor Lombar , Vértebras Lombares , Adulto , Amoxicilina/administração & dosagem , Amoxicilina/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Dor Crônica/diagnóstico , Dor Crônica/tratamento farmacológico , Dor Crônica/etiologia , Avaliação da Deficiência , Método Duplo-Cego , Feminino , Humanos , Dor Lombar/diagnóstico , Dor Lombar/tratamento farmacológico , Dor Lombar/etiologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Masculino , Pessoa de Meia-Idade , Noruega , Medição da Dor/métodos , Resultado do Tratamento
2.
Blood Adv ; 3(7): 945-951, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30923048

RESUMO

HLA-DRB3*01:01 is a predisposing factor for human platelet antigen 1a (HPA-1a) immunization, which is responsible for most cases of fetal and neonatal alloimmune thrombocytopenia. The aim of this study was to investigate if the HLA-DRB3*01:01 allele imposes a dose-dependent effect on anti-HPA-1a levels and neonatal platelet counts. One hundred and thirty HPA-1a-immunized women were divided into 3 groups: HLA-DRB3*01:01 negative, HLA-DRB3*01:01 hemizygous or heterozygous, and HLA-DRB3*01:01 homozygous. The dose of the HLA-DRB3*01:01 allele was determined by sequencing exon 2 of the HLA-DRB3 gene followed by HLA-DRB3 and HLA-DRB1 typing of selected samples. Anti-HPA-1a levels at time of delivery and neonatal platelet counts were compared among groups. There was a significant dose-dependent effect of the HLA-DRB3*01:01 allele on anti-HPA-1a levels (global P value [P global] = .0032). Median (range) anti-HPA-1a levels were 1.5 IU/mL (0.0-19.0 IU/mL), 21.1 IU/mL (0.0-1967 IU/mL), and 43.7 IU/mL (1.0-980 IU/mL) in women with 0, 1, and 2 copies of the HLA-DRB3*01:01 allele, respectively. There was also a significant, but opposite, dose-dependent effect of the mother's HLA-DRB3*01:01 allele on the platelet count of the newborn (P global = .0155). Median (range) neonatal platelet counts were 241 × 109/L (59 × 109/L to 393 × 109/L), 107 × 109/L (4 × 109/L to 387 × 109/L) and 32 × 109/L (4 × 109/L to 352 × 109/L) for newborns of mothers with 0, 1, and 2 copies of the HLA-DRB3*01:01 allele, respectively. Thus, the HLA-DRB3*01:01 allele exhibits a dose-dependent impact on maternal anti-HPA-1a levels in HPA-1a-immunized women.

3.
J Rheumatol ; 45(9): 1211-1219, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29858238

RESUMO

OBJECTIVE: We aimed to jointly investigate the role of antipeptidyl arginine deiminase type 4 antibodies (anti-PAD4) and polymorphisms in the PADI4 gene together with clinical variables in rheumatoid arthritis (RA). METHODS: Serum IgG autoantibodies to human recombinant PAD4 were identified by DELFIA technique in 745 patients with RA (366 available from previous studies). Genotyping of PADI4 was performed using TaqMan assays in 945 patients and 1118 controls. Clinical data, anticitrullinated protein antibodies (ACPA) status, shared epitope status, and a combined genetic risk score were also available. RESULTS: Anti-PAD4 antibodies were detected in 193 (26%) of 745 patients with RA; 149 (77%) of these were also ACPA-positive. No association was observed between anti-PAD4 status and clinical characteristics, PADI4 polymorphisms, or genetic risk scores after stratification for ACPA status. CONCLUSION: Taken together, the results from these combined serological, genetic, and clinical analyses suggest that anti-PAD4 appears to be a bystander autoantibody with no current clinical utility in RA.


Assuntos
Artrite Reumatoide/genética , Autoanticorpos , Polimorfismo de Nucleotídeo Único , Desiminases de Arginina em Proteínas/genética , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Epitopos , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Desiminases de Arginina em Proteínas/imunologia
4.
Cancer Res ; 76(18): 5326-36, 2016 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-27406829

RESUMO

By affecting immunological presentation, the presence of cytomegalovirus in some glioblastomas may impact progression. In this study, we examined a hypothesized role for natural killer (NK) cells in impacting disease progression in this setting. We characterized 108 glioblastoma patients and 454 healthy controls for HLA-A,-B,-C, NK-cell KIR receptors, and CMV-specific antibodies and correlated these metrics with clinical parameters. Exome sequences from a large validation set of glioblastoma patients and control individuals were examined from in silico databases. We demonstrated that the KIR allele KIR2DS4*00101 was independently prognostic of prolonged survival. KIR2DS4*00101 displayed 100% concordance with cognate HLA-C1 ligands in glioblastoma patients, but not controls. In the context of both HLA-C1/C2 ligands for the KIR2DS4 receptor, patient survival was further extended. Notably, all patients carrying KIR2DS4*00101 alleles were CMV seropositive, but not control individuals, and exhibited increased NK-cell subpopulations, which expressed the cytotoxicity receptors CD16, NKG2D, and CD94/NKG2C. Finally, healthy controls exhibited a reduced risk for developing glioblastoma if they carried two KIR2DS4*00101 alleles, where protection was greatest among Caucasian individuals. Our findings suggest that KIR2DS4*00101 may offer a molecular biomarker to identify intrinsically milder forms of glioblastoma. Cancer Res; 76(18); 5326-36. ©2016 AACR.


Assuntos
Biomarcadores Tumorais/imunologia , Neoplasias Encefálicas/imunologia , Glioblastoma/imunologia , Células Matadoras Naturais/imunologia , Receptores KIR/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/virologia , Criança , Infecções por Citomegalovirus/complicações , Feminino , Citometria de Fluxo , Glioblastoma/mortalidade , Glioblastoma/virologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Modelos de Riscos Proporcionais , Adulto Jovem
5.
Rheumatology (Oxford) ; 54(3): 528-35, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25187641

RESUMO

OBJECTIVE: The Norwegian nationwide MCTD cohort was established to obtain unbiased data on key disease issues, and thereby reappraise the concept of MCTD. In the current study, the aims were to obtain detailed HLA profile data on the large Norwegian MCTD cohort and compare these with the HLA profiles of ethnically matched healthy controls and related CTD controls. METHODS: HLA profiles, determined by sequence-based typing of HLA-B* and DRB1*, were compared between four control groups of Norwegian ancestry, SLE (n = 96), SSc (n = 95), PM/DM (n = 84), healthy individuals (n = 282), the complete MCTD cohort (n = 155) and MCTD subsets defined by key clinical parameters. RESULTS: HLA-B*08 [odds ratio (OR) 2.05, P = 1.31 × 10(-4)) and DRB1*04:01 (OR 2.82, P = 3.64 × 10(-8)) were identified as risk alleles for MCTD, while DRB1*04:04, DRB1*13:01 and DRB1*13:02 were protective. Risk alleles for SLE and PM/DM were B*08 and DRB1*03:01. SSc risk was associated with DRB1*08:01. Analyses of MCTD subsets identified B*18 [OR 3.32 (95% CI 1.38, 8.01)] and DRB1*03:01 [OR 1.83 (95% CI 1.03, 3.25)] as independent risk factors for lung fibrosis. CONCLUSION: Novel HLA alleles associated with MCTD and disease subsets were identified and DRB1*04:01 was confirmed as a major risk allele. Altogether, the data reinforce the notion of MCTD as a disease entity distinct from SLE, SSc and PM/DM.


Assuntos
Dermatomiosite/genética , Antígenos HLA/genética , Lúpus Eritematoso Sistêmico/genética , Doença Mista do Tecido Conjuntivo/genética , Polimiosite/genética , Escleroderma Sistêmico/genética , Transcriptoma/genética , Adolescente , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Dermatomiosite/epidemiologia , Feminino , Antígenos HLA-B/genética , Cadeias HLA-DRB1/genética , Humanos , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/epidemiologia , Doença Mista do Tecido Conjuntivo/etnologia , Polimiosite/epidemiologia , Polimiosite/etnologia , Fatores de Risco , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/etnologia , Adulto Jovem
6.
Curr Biol ; 24(21): 2518-25, 2014 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-25447991

RESUMO

BACKGROUND: Rapa Nui (Easter Island), located in the easternmost corner of the Polynesian Triangle, is one of the most isolated locations on the planet inhabited by humans. Archaeological and genetic evidence suggests that the island was first colonized by Polynesians around AD 1200, during their eastward expansion. Although it remains contentious whether Polynesians reached South America, suggestive evidence has been brought forward supporting the possibility of Native American contact prior to the European "discovery" of the island in AD 1722. RESULTS: We generated genome-wide data for 27 Rapanui. We found a mostly Polynesian ancestry among Rapanui and detected genome-wide patterns consistent with Native American and European admixture. By considering the distribution of local ancestry tracts of eight unrelated Rapanui, we found statistical support for Native American admixture dating to AD 1280-1495 and European admixture dating to AD 1850-1895. CONCLUSIONS: These genetic results can be explained by one or more pre-European trans-Pacific contacts.


Assuntos
Índios Norte-Americanos/genética , Grupo com Ancestrais Oceânicos/genética , Migração Humana , Humanos , Polinésia/etnologia
7.
BMC Cancer ; 14: 845, 2014 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-25407022

RESUMO

BACKGROUND: The procoagulant state in cancer increases the thrombotic risk, but also supports tumor progression. To investigate the molecular mechanisms controlling cancer and hemostasis, we conducted a case-control study of genotypic and phenotypic variables of the tissue factor (TF) pathway of coagulation in breast cancer. METHODS: 366 breast cancer patients and 307 controls were genotyped for SNPs (n = 41) in the F2, F3 (TF), F5, F7, F10, TFPI and EPCR genes, and assayed for plasma coagulation markers (thrombin generation, activated protein C (APC) resistance, D-dimer, antithrombin, protein C, protein S, and TF pathway inhibitor (TFPI)). Associations with breast cancer were evaluated using logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs), or the chi-square test. RESULTS: Four SNPs in F5 (rs12120605, rs6427202, rs9332542 and rs6427199), one in F10 (rs3093261), and one in EPCR (rs2069948) were associated with breast cancer. EPCR rs2069948 was associated with estrogen receptor (ER) and progesterone receptor (PR) positivity, while the SNPs in F5 appeared to follow hormone receptor negative and triple negative patients. The prothrombotic polymorphisms factor V Leiden (rs6025) and prothrombin G20210A (rs1799963) were not associated with breast cancer. High APC resistance was associated with breast cancer in both factor V Leiden non-carriers (OR 6.5, 95% CI 4.1-10.4) and carriers (OR 38.3, 95% CI 6.2-236.6). The thrombin parameters short lag times (OR 5.8, 95% CI 3.7-9.2), short times to peak thrombin (OR 7.1, 95% CI 4.4-11.3), and high thrombin peak (OR 6.1, 95% CI 3.9-9.5) predicted presence of breast cancer, and high D-dimer also associated with breast cancer (OR 2.0, 95% CI 1.3-3.3). Among the coagulation inhibitors, low levels of antithrombin associated with breast cancer (OR 5.7, 95% CI 3.6-9.0). The increased coagulability was not explained by the breast cancer associated SNPs, and was unaffected by ER, PR and triple negative status. CONCLUSIONS: A procoagulant phenotype was found in the breast cancer patients. Novel associations with SNPs in F5, F10 and EPCR to breast cancer susceptibility were demonstrated, and the SNPs in F5 were confined to hormone receptor negative and triple negative patients. The study supports the importance of developing new therapeutic strategies targeting coagulation processes in cancer.


Assuntos
Antígenos CD/genética , Coagulação Sanguínea/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Fator V/genética , Fator X/genética , Polimorfismo Genético , Receptores de Superfície Celular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Receptor de Proteína C Endotelial , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Hemostasia , Humanos , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Polimorfismo de Nucleotídeo Único , Risco , Transdução de Sinais , Tromboplastina/metabolismo
8.
BMC Neurol ; 14: 196, 2014 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-25274070

RESUMO

BACKGROUND: Several environmental exposures, including infection with Epstein-Barr virus, low levels of vitamin D and smoking are established risk factors for multiple sclerosis (MS). Also, high hygienic standard and infection with parasites have been proposed to influence MS risk. The aim of this study was to investigate the influence of various environmental exposures on MS risk in a Norwegian cohort, focusing on factors during childhood related to the hygiene hypothesis. METHODS: A questionnaire concerning environmental exposures, lifestyle, demographics and comorbidity was administrated to 756 Norwegian MS patients and 1090 healthy controls. Logistic regression was used to calculate odds ratio (OR) with 95% confidence interval (CI) for the risk of MS associated with the variables infectious mononucleosis, severe infection during childhood, vaccination and animals in the household during childhood. Age, gender, HLA-DRB1*15:01, smoking and infectious mononucleosis were included as covariates. General environmental exposures, including tobacco use, were also evaluated. RESULTS: Infectious mononucleosis was confirmed to be significantly associated with increased MS risk, also after adjusting for the covariates (OR = 1.79, 95% CI: 1.12-2.87, p = 0.016). The controls more often reported growing up with a cat and/or a dog in the household, and this was significant for ownership of cat also after adjusting for the covariates (OR = 0.56, 95% CI: 0.40-0.78, p = 0.001). More patients than controls reported smoking and fewer patients reported snuff use. CONCLUSIONS: In this Norwegian MS case-control study of environmental exposures, we replicate that infectious mononucleosis and smoking are associated with increased MS risk. Our data also indicate a protective effect on MS of exposure to cats during childhood, in accordance with the hypothesis that risk of autoimmune diseases like MS may increase with high hygienic standard.


Assuntos
Exposição Ambiental , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/etiologia , Adulto , Animais , Estudos de Casos e Controles , Gatos , Cães , Feminino , Humanos , Mononucleose Infecciosa/complicações , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Razão de Chances , Animais de Estimação , Fatores de Risco , Fumar/efeitos adversos , Inquéritos e Questionários , Adulto Jovem
9.
Clin Gastroenterol Hepatol ; 12(6): 1019-28, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24076415

RESUMO

BACKGROUND & AIMS: Little is known about nongenetic risk factors for primary sclerosing cholangitis (PSC), except a possible protective effect of smoking. We investigated the relationship between environmental risk factors and susceptibility to PSC. METHODS: A questionnaire was distributed to patients with PSC, recruited from Oslo University Hospital Rikshospitalet in Norway through 2011, and randomly chosen individuals from the Norwegian Bone Marrow Donor Registry (control subjects). Data were analyzed from 240 patients with PSC and 245 control subjects, matched for gender and age. RESULTS: A lower proportion of patients with PSC were daily coffee drinkers than control subjects, both currently (76% vs 86%; odds ratio [OR], 0.52; 95% confidence interval [CI], 0.32-0.82; P = .006) and at the age of 18 years (35% vs 49%; OR, 0.58; 95% CI, 0.40-0.83; P = .003). The associations were mainly attributed to differences observed in men. Twenty percent of the patients were ever (current or former) daily smokers compared with 43% of control subjects (OR, 0.33; 95% CI, 0.22-0.50; P < .001). Ever daily smoking before PSC diagnosis was associated with older age at diagnosis (42 years vs 32 years; P < .001). Ever daily smoking (P < .001) and being a coffee drinker at the age of 18 years (P = .048) were independently and negatively associated with PSC. Fewer female patients with PSC than control subjects reported ever use of hormonal contraception (51% vs 85%; P < .001). Among female patients, there was a strong correlation between increasing number of children before the diagnosis of PSC and increasing age at diagnosis (r = 0.63; P < .001). CONCLUSIONS: Coffee consumption and smoking might protect against development of PSC. In women, the disease might be influenced by hormonal factors.


Assuntos
Colangite Esclerosante/epidemiologia , Café , Suscetibilidade a Doenças , Hormônios/fisiologia , Fumar , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Medição de Risco , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários , Adulto Jovem
10.
BMC Musculoskelet Disord ; 14: 105, 2013 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-23522322

RESUMO

BACKGROUND: Inflammatory and matrix degrading gene variants have been reported to be associated with disc degeneration. Some of these variants also modulate peripheral pain. This study examines the association of these genetic variants with radiographic lumbar disc degeneration and changes in pain and disability at long-term after surgical and cognitive behavioural management. METHODS: 93 unrelated patients with chronic low back pain (CLBP) for duration of >1 year and lumbar disc degeneration were treated with lumbar fusion or cognitive intervention and exercises. Standardised questionnaires included the Oswestry Disability Index (ODI) and Visual Analog Score (VAS) for CLBP, were filled in by patients both at baseline and at 9 years follow-up. Degenerative changes at baseline Magnetic Resonance Imaging and Computed Tomography scans, were graded as moderate and severe (N=79). Yield and quality of blood and saliva DNA was assessed by nano drop spectrophotometry. Eight SNPs in 5 inflammatory and matrix degrading genes were successfully genotyped. Single marker and haplotype association with severity of degeneration, number of discs involved, changes in ODI and VAS CLBP, was done using Haploview, linear regression and R-package Haplostats. RESULTS: Association analysis of individual SNPs revealed association of IL18RAP polymorphism rs1420100 with severe degeneration (p = 0.05) and more than one degenerated disc (p = 0.02). From the same gene two SNPs, rs917997 and rs1420106, were found to be in strong linkage disequilibrium (LD) and were associated with post treatment improvement in disability (p = 0.02). Haplotype association analysis of 5 SNPs spanning across IL18RAP, IL18R1 and IL1A genes revealed significant associations with improvement in disability (p=0.02) and reduction in pain (p=0.04). An association was found between MMP3 polymorphism rs72520913 and improvement in pain (p = 0.03) and with severe degeneration (p = 0.006). CONCLUSIONS: The findings of the current study suggest a role of variation at inflammatory and matrix degrading genes with severity of lumbar disc degeneration, pain and disability.


Assuntos
Dor Crônica/genética , Estudos de Associação Genética/métodos , Interleucina-18/genética , Degeneração do Disco Intervertebral/genética , Dor Lombar/genética , Metaloproteinase 3 da Matriz/genética , Adulto , Dor Crônica/diagnóstico por imagem , Dor Crônica/cirurgia , Estudos de Coortes , Feminino , Seguimentos , Variação Genética/genética , Humanos , Inflamação/diagnóstico por imagem , Inflamação/genética , Inflamação/cirurgia , Mediadores da Inflamação/fisiologia , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Dor Lombar/diagnóstico por imagem , Dor Lombar/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Polimorfismo de Nucleotídeo Único/genética , Estudos Prospectivos , Radiografia , Fusão Vertebral/tendências , Resultado do Tratamento
11.
BMC Musculoskelet Disord ; 13: 76, 2012 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-22612913

RESUMO

BACKGROUND: Treatment outcome of low back pain (LBP) is associated with inter-individual variations in pain relief and functional disability. Genetic variants of catechol-O-methyltransferase (COMT) gene have previously been shown to be associated with pain sensitivity and pain medication. This study examines the association between COMT polymorphisms and 7-11 year change in Oswestry Disability Index (ODI) and Visual Analog Score (VAS) for LBP as clinical outcome variables in patients treated with surgical instrumented lumbar fusion or cognitive intervention and exercise. METHODS: 93 unrelated patients with chronic LBP for duration of >1 year and lumbar disc degeneration (LDD) were treated with lumbar fusion (N = 60) or cognitive therapy and exercises (N = 33). Standardised questionnaires assessing the ODI, VAS LBP, psychological factors and use of analgesics, were answered by patients both at baseline and at 7-11 years follow-up. Four SNPs in the COMT gene were successfully genotyped. Single marker as well as haplotype association with change in ODI and VAS LBP, were analyzed using Haploview, linear regression and R-package Haplostats. P-values were not formally corrected for multiple testing as this was an explorative study. RESULTS: Association analysis of individual SNPs adjusted for covariates revealed association of rs4633 and rs4680 with post treatment improvement in VAS LBP (p = 0.02, mean difference (ß) = 13.5 and p = 0.02, ß = 14.2 respectively). SNPs, rs4633 and rs4680 were found to be genotypically similar and in strong linkage disequilibrium (LD). A significant association was found with covariates, analgesics (p = 0.001, ß = 18.6); anxiety and depression (p = 0.008, ß = 15.4) and age (p = 0.03, mean difference per year (ß) = 0.7) at follow-up. There was a tendency for better improvement among heterozygous patients compared to the homozygous. No association was observed for the analysis of the common haplotypes, these SNPs were situated on. CONCLUSIONS: Results suggest an influence of genetic variants of COMT gene in describing the variation in pain after treatment for low back pain. Replication in large samples with testing for other pain related genes is warranted.


Assuntos
Catecol O-Metiltransferase/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Dor Lombar/genética , Polimorfismo de Nucleotídeo Único , Adulto , Avaliação da Deficiência , Feminino , Genótipo , Humanos , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/fisiopatologia , Degeneração do Disco Intervertebral/cirurgia , Desequilíbrio de Ligação/genética , Dor Lombar/fisiopatologia , Dor Lombar/cirurgia , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Projetos de Pesquisa , Fusão Vertebral , Inquéritos e Questionários
12.
Open Orthop J ; 6: 164-71, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22550553

RESUMO

OBJECTIVES: To examine association of candidate genetic variants in structural, inflammatory, matrix modifying, vitamin D receptor genes and variants associated with osteoarthritis, with surgical candidates and surgical patients with lumbar disc degeneration (LDD), in light of their previously reported susceptibility for LDD. METHODS: Genotyping of 146 Norwegian LDD patients and 188 Norwegian controls was performed for 20 single-nucleotide polymorphisms (SNPs) from collagen, aggrecan, interleukin, VDR, MMP3 and COX2 genes and 7 SNPs from osteoarthritic genes. RESULTS: The neighboring genes IL18R1 and IL18RAP polymorphisms (rs2287037 and rs1420100), showed a statistically non-significant risk for developing LDD (OR 1.36 [95 % CI 0.99 - 1.87]; p=0.06 and OR 1.33 [95 % CI 0.98-1.81]; p=0.07). Homozygosity of these risk alleles was associated with LDD (p=0.023 and p=0.027). The non-risk alleles at these SNPs were situated on a haplotype negatively associated with LDD (p=0.008). Carriage of at least one non-risk allele at both loci also reduces the risk of developing LDD (OR 0.51 [95 % CI 0.33-0.80]; p=0.003). CONCLUSION: Our findings support the polygenic nature of LDD and suggest that variation in interleukin 18 receptor genes could affect the risk of severe LDD and associated low back pain.

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