RESUMO
Previous studies have found higher levels of serum malondialdehyde (MDA) in hepatocellular carcinoma (HCC) patients compared to healthy controls and higher MDA concentrations in tumoral tissue of HCC patients than in non-tumoral tissue. However, the association between pre-transplant serum levels of MDA and survival in HCC patients after liver transplantation (LT) has not been described, and the aim of the present study was to determine whether such an association exists. In this observational study we measured serum MDA levels in 127 patients before LT. We found higher pre-LT serum MDA levels in 15 non-surviving than in 112 surviving patients one year after LT (p = 0.02). Exact binary logistic regression analysis revealed that pre-LT serum levels of MDA over 3.37 nmol/mL were associated with mortality after one year of LT (Odds ratio = 5.38; 95% confidence interval (CI) = from 1.580 to infinite; p = 0.007) adjusting for age of the deceased donor. The main finding of our study was that there is an association between serum MDA levels before LT for HCC and 1-year survival after LT.
Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Transplante de Fígado , Malondialdeído/sangue , Adulto , Idoso , Carcinoma Hepatocelular/sangue , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Curva ROC , Resultado do TratamentoRESUMO
A national, multicenter, retrospective study was conducted to assess the results obtained for liver transplant recipients with conversion to everolimus in daily practice. The study included 477 recipients (481 transplantations). Indications for conversion to everolimus were renal dysfunction (32.6% of cases), hepatocellular carcinoma (HCC; 30.2%; prophylactic treatment for 68.9%), and de novo malignancy (29.7%). The median time from transplantation to conversion to everolimus was 68.7 months for de novo malignancy, 23.8 months for renal dysfunction, and 7.1 months for HCC and other indications. During the first year of treatment, mean everolimus trough levels were 5.4 (standard deviation [SD], 2.7) ng/mL and doses remained stable (1.5 mg/day) from the first month after conversion. An everolimus monotherapy regimen was followed by 28.5% of patients at 12 months. Patients with renal dysfunction showed a glomerular filtration rate (4-variable Modification of Diet in Renal Disease) increase of 10.9 mL (baseline mean, 45.8 [SD, 25.3] versus 57.6 [SD, 27.6] mL/minute/1.73 m(2) ) at 3 months after everolimus initiation (P < 0.001), and 6.8 mL at 12 months. Improvement in renal function was higher in patients with early conversion (<1 year). Adverse events were the primary reason for discontinuation in 11.2% of cases. The probability of survival at 3 years after conversion to everolimus was 83.0%, 71.1%, and 59.5% for the renal dysfunction, de novo malignancy, and HCC groups, respectively. Everolimus is a viable option for the treatment of renal dysfunction, and earlier conversion is associated with better recovery of renal function. Prospective studies are needed to confirm advantages in patients with malignancy.
Assuntos
Substituição de Medicamentos , Everolimo/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Rim/efeitos dos fármacos , Transplante de Fígado , Adolescente , Adulto , Idoso , Criança , Monitoramento de Medicamentos , Everolimo/efeitos adversos , Everolimo/sangue , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/sangue , Rim/fisiopatologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Espanha , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Toll-like receptors trigger the innate immune response by activating various cell types such us macrophages and lymphocytes. We genotyped SNV of TLR3, TRL7, TLR8 and TLR10 in 863 Spanish and 150 Italian patients with Meniere's disease (MD) and 1,013 controls by using Taqman assays. Real-Time qPCR was used to measure the expression level of TLR10 in peripheral blood leukocytes. The overall dataset showed that the C allele and the CC genotype of rs11096955 in TLR10 gene were more commonly observed in controls than patients (corrected p = 1 × 10(-3), OR = 0.68 [95 % confidence interval, 0.54-0.84] for CC genotype; corrected p = 1.5 × 10(-5), OR = 0.75 [0.66-0.85] for allele C). Moreover, the CC genotype was more frequent in patients with uni- (19 %) than bilateral sensorineural hearing loss (SNHL) (13 %). Logistic regression demonstrated that the time since the onset of MD, Tumarkin crises, hearing stage and rs11096955 were independent factors influencing the risk of bilateral SNHL. In addition, rs11096955 influenced hearing loss progression in patients with bilateral MD. No change in expression of TLR10 was observed according to CC, CA or AA genotypes. Our data suggest that allelic variants of TLR10 gene may influence the susceptibility and time-course of hearing loss of MD in the European population.
Assuntos
Biomarcadores Tumorais/genética , Perda Auditiva Neurossensorial/genética , Doença de Meniere/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor 10 Toll-Like/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Perda Auditiva Neurossensorial/patologia , Humanos , Masculino , Doença de Meniere/patologia , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/genética , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor 3 Toll-Like/genética , Receptor 7 Toll-Like/genética , Receptor 8 Toll-Like/genética , População Branca , Adulto JovemRESUMO
Variability in acute immune response genes could determine susceptibility or prognosis for Ménière's disease (MD). The cytokines tumor necrosis factor α (TNFα), macrophage migration inhibitory factor (MIF) and interferon γ (INFγ) are proinflammatory cytokines of the innate immune response. These cytokines mediate inflammation and have been previously associated with the inflammatory process in several autoimmune diseases. We investigated the association between functional allelic variants of MIF (rs35688089), IFNG (rs2234688) and TNFA (rs1800629) in patients with MD. In addition to testing these variants for an association with disease, we also tested for an association with clinical aspects of disease progression, such as persistence of vertigo and the sensorineural hearing loss. A total of 580 patients with diagnosis of definite MD, according to the diagnostic scale of the American Academy of Otolaryngology-Head and Neck Surgery, and 552 healthy controls were included. DNA samples from a set of 291 American patients were used to confirm the results obtained in the MIF gene in our Spanish cohort. Although we found a significant association with the allele containing five repeats of CATT within the MIF gene in patients with MD in the Spanish cohort [corrected p = 0.008, OR = 0.69 (95 % CI, 0.54-0.88)], this finding could not be replicated in the American set. Moreover, no genetic associations for variants in either the TNFA or IFNG genes and MD were found. These results support the conclusion that functional variants of MIF, INFG, and TFNA genes are not associated with disease susceptibility or hearing loss progression in patients with MD.
Assuntos
Predisposição Genética para Doença/genética , Perda Auditiva Neurossensorial/genética , Interferon gama/genética , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Doença de Meniere/genética , Fragmentos de Peptídeos/genética , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Coortes , Comparação Transcultural , Progressão da Doença , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Espanha , Estados Unidos , Adulto JovemRESUMO
OBJECTIVE: To determine the role of Class II HLAs in SSc patients from Italy and Spain and in SSc patients of Caucasian ancestry. METHODS: Nine hundred and forty-four SSc patients (Italy 392 patients; Spain 452 patients) and 1320 ethnically matched healthy controls (Italy 398 patients; Spain 922 patients) were genotyped up to the fourth digit by PCR with sequence-specific oligonucleotides for HLA-DRB1, DQA1 and DQB1 loci. Patients included 390 ACA-positive and 254 anti-topo I-positive subjects. Associations between SSc or SSc-specific antibodies and HLA alleles or HLA haplotypes were sought via the chi-square test after 10 000-fold permutation testing. A meta-analysis including this study cohort and other Caucasoids samples was also conducted. RESULTS: In both the cohorts, the strongest association was observed between the HLA-DRB1*1104 allele and SSc or anti-topo I antibodies. The HLA-DRB1*1104 -DQA1*0501 -DQB1*0301 haplotype was overrepresented in Italian [odds ratio (OR) = 2.069, 95% asymptotic CIs (CI(95)) 1.486, 2.881; P < 0.001] and in Spanish patients (OR = 6.707, CI(95) 3.974, 11.319; P < 0.001) as well as in anti-topo-positive patients: Italy (OR = 2.642, CI(95) 1.78, 3.924; P < 0.001) and Spain (OR = 20.625, CI(95) 11.536, 36.876; P < 0.001). In both the populations we also identified an additional risk allele (HLA-DQB1*03) and a protective allele (HLA-DQB1*0501) in anti-topo-positive patients. The meta-analysis showed different statistically significant associations, the most interesting being the differential association between HLA-DRB1*01 alleles and ACAs (OR = 1.724, CI(95) 1.482, 2.005; P < 0.001) or topo I antibodies (OR = 0.5, CI(95) 0.384, 0.651; P < 0.001). CONCLUSIONS: We describe multiple robust associations between SSc and HLA Class II antigens in Caucasoids that may help to understand the genetic architecture of SSc.
Assuntos
Antígenos HLA-D/genética , Escleroderma Sistêmico/genética , Autoanticorpos/análise , Estudos de Casos e Controles , Predisposição Genética para Doença , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Teste de Histocompatibilidade/métodos , Humanos , Itália/epidemiologia , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/imunologia , Espanha/epidemiologiaRESUMO
The use of ICTs provides autonomy, equity, and social inclusion to people with visual disabilities. The National Organization of the Spanish Blind (ONCE) offers its 70,462 legally-blind people the necessary resources for the usability of ICTs. Still, most individuals with visual disabilities do not have a similar support system. This research aims to expose and make visible the importance and need for ICTs usage in this group. The qualitative approach has allowed the modeling of a contextualized inductive process through two heterogeneous discussion groups: eight individuals with legal blindness and six with moderate visual impairment, as well as three in-depth interviews with experts in typhlotechnology, accessibility, and low vision. The following has been verified: there is a lot of misinformation among people with visual disabilities outside the coverage of ONCE; accessibility is still not a priority for companies and institutions when creating and developing products and services with Design for All; the need for more professionals to advise and train users with blindness and low vision is clear. In Spain, there are almost a million visually-impaired people not affiliated with ONCE, for whom access to technical aids and digital literacy is a priority problem in which the Government should intervene.
Assuntos
Pessoas com Deficiência , Baixa Visão , Pessoas com Deficiência Visual , Cegueira , Humanos , EspanhaRESUMO
BACKGROUND: Autoimmune diseases with elevated circulating autoantibodies drive tissue damage and the onset of disease. The Fcγ receptors bind IgG subtypes modulating the clearance of circulating immune complexes (CIC). The inner ear damage in Ménière's disease (MD) could be mediated by an immune response driven by CIC. We examined single-nucleotide polymorphism (SNPs) in the CD16A and CD32 genes in patients with MD which may determine a Fcγ receptor with lower binding to CIC. METHODS: The functional CD16A (FcγRIIIa*559A > C, rs396991) and CD32A (FcγRIIa*519A > G, rs1801274) SNPs were analyzed using PCR-based TaqMan Genotyping Assay in two cohorts of 156 mediterranean and 112 Galicia patients in a case-control study. Data were analyzed by χ2 with Fisher's exact test and Cochran-Armitage trend test (CATT). CIC were measured by ELISA for C1q-binding CIC. RESULTS: Elevated CIC were found in 7% of patients with MD during the intercrisis period. No differences were found in the allelic frequency for rs396991 or rs1801274 in controls subjects when they were compared with patients with MD from the same geographic area. However, the frequency of AA and AC genotypes of CD16A (rs396991) differed among mediterranean and Galicia controls (Fisher's test, corrected p = 6.9 × 10-4 for AA; corrected p = 0.02 for AC). Although genotype AC of the CD16A receptor was significantly more frequent in mediterranean controls than in patients, [Fisher's test corrected p = 0.02; OR = 0.63 (0.44-0.91)], a genetic additive effect for the allele C was not observed (CATT, p = 0.23). Moreover, no differences were found in genotype frequencies for rs396991 between patients with MD and controls from Galicia (CATT, p = 0.14). The allelic frequency of CD32 (rs1801274) was not different between patients and controls either in mediterranean (p = 0.51) or Galicia population (p = 0.11). CONCLUSIONS: Elevated CIC are not found in most of patients with MD. Functional polymorphisms of CD16A and CD32 genes are not associated with onset of MD.
Assuntos
Complexo Antígeno-Anticorpo/sangue , Doença de Meniere/genética , Polimorfismo de Nucleotídeo Único , Receptores de IgG/genética , Adulto , Idoso , Doenças Autoimunes/sangue , Doenças Autoimunes/genética , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Doença de Meniere/sangue , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
If the workplace environment is good, the health and well-being of employees will be good too. This research aims to distinguish whether there are differences when it comes to being directed by a man or a woman and whether this affects employees. An ad hoc questionnaire was applied, collecting personal information and including the MLQ-6 S. It was sent by mail and answered by 549 employees of 16 companies in the Basque Country, Spain. A total of 277 (50.5%) men and 272 (49.5%) women participated, among whom there were 63 managers. The methodology shows a double perspective of how employees understand and perceive the differences between male and female business leaders and how managers see themselves exercising this leadership. No significant differences have been perceived. Both men and women believe they make their employees feel good about exercising leadership (M = 42.11%, W = 48.00%) quite often. Employed women consider it more challenging to become leaders and reconcile their work-life. Men do not think so. Communication is the tool that women managers know best how to handle and where men seem to fail more. Working on it could achieve more business success and better health in employees.
Assuntos
Liderança , Local de Trabalho , Comércio , Comunicação , Feminino , Humanos , Masculino , EspanhaRESUMO
hGLUTEN is a technological solution capable of detecting gluten and spoiled food. We measured the social impact of the hGLUTEN tool using two Likert scale surveys with two groups: professionals (engineers/chefs) and end-users. These data have been assessed in accordance with the social impact indicators defined for the Key Impact Pathways introduced by the European Commission for Horizon Europe and the criteria of the Social Impact Open Repository (SIOR). A total of 85% of users, 100% of engineers and 68% of professional chefs consider it very relevant to participate and give their opinion in research projects, which shows the increasingly high level of involvement of the general population. A total of 88% of users were unaware of other applications that detect gluten and were more dependent on guidelines provided by allergy associations and expiry dates of foodstuffs. In addition, only 5% of professional chefs said they were aware of other technology capable of detecting gluten in food, which may indicate a large economic market and good commercialisation possibilities for the tool in the future. Finally, the inclusion of tools to motivate users to promote it has been identified as an area for improvement, which could mean that it should be made more visible in the media to increase its impact and influence.
Assuntos
Mudança Social , Europa (Continente) , Humanos , Inquéritos e QuestionáriosRESUMO
Although prior research has extensively examined the association of emotional intelligence (EI) with various job attitudes (e.g., job satisfaction), empirical and systematic investigation of this link within military institutions has captured considerably less attention. The present research analyzed the relationship between EI, teamwork communication, and job satisfaction among Spanish military cadets. We tested the potential unique contribution of EI to job satisfaction over and above demographics (i.e., gender and age), proactive personality, and resilience. Moreover, we also examined whether EI was indirectly linked to job satisfaction via its relationship with teamwork communication. A sample of 363 cadet officers of the Spanish General Military Academy completed questionnaires assessing EI, teamwork communication, proactive personality, resilience, and job satisfaction. Hierarchical regression analysis revealed that EI exhibited incremental variance (ΔR 2 = 5.2%) in predicting job satisfaction (B = 0.539, 95% CI [0.306,0.771]) even after accounting for demographics, proactive personality, and resilience. Additionally, mediation analysis showed that the association of EI with job satisfaction was partially driven by enhanced teamwork communication. This research provides empirical evidence suggesting a pathway (i.e., effective teamwork communication) through which EI could help military cadets to experience higher job satisfaction. Implications for future academic programs including EI and teamwork communication to promote positive job attitudes among military personnel are discussed.
RESUMO
Crohn's Disease is one of the two major forms of the Inflammatory Bowel Diseases and, although the etiology is not completely understood, the confluence of environmental and genetic factors has been demonstrated. The aim of this study was to determine the distribution of TLR4 variants in a Spanish cohort of Crohn's Disease patients and their relation with phenotype and common NOD2 variants. A total of 371 Crohn's Disease (CD) patients and 636 healthy controls (HC) were included. Single Nucleotide Polimorphisms (SNPs) in TLR4 (D299G and T399I) and NOD2 (R702W and G908R) detection was performed by a Taqman(®) Allelic Discrimination Assay. 1007insC NOD2 variant was analyzed using a PCR combined with fluorescent technology and the different alleles were determined depending on the PCR products size. D299G and T399I were related to CD only in patients carrying NOD2 variants (NOD2+/TLR4+ haplotype) (p=0.036; OR=1.924), increasing the risk to develop CD when 1007insC and TLR4 variants were both present (OR=4.886). We also described a strong association between mutant NOD2 and CD risk (p<0.001, OR=3.214). R702W, G908R and 1007insC were associated when they were considered separately (p<0.001; p=0.002; p<0.001, respectively). Moreover, the patients carrying any mutant D299G or T399I polymorphisms were predisposed to develop a stricturing disease (p=0.013; OR=2.391), especially in the presence of NOD2 mutation (p=0.002; OR=4.989). In this study, ileal disease was also associated with the presence of at least one NOD2 susceptibility allele (p=0.001; OR=3.838) and, the risk of ileal CD was increased if TLR4 variants were presents (p<0.050; OR=4.160). TLR4 variants were related to bowel perforation, independently of NOD2.
Assuntos
Doença de Crohn/genética , Proteína Adaptadora de Sinalização NOD2/genética , Receptor 4 Toll-Like/genética , Adulto , Estudos de Coortes , Epistasia Genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Doenças do Íleo/genética , Masculino , Mutação , Fenótipo , Polimorfismo de Nucleotídeo Único , Risco , Espanha , População Branca/genética , Adulto JovemRESUMO
The principal goal of this study was to determine the effect of the photoperiod on oxidative damage biomarkers in rats submitted to different light/darkness patterns, in a hyperlipidemic nephropathy model (induced by adriamycin), as well as its possible relationship with melatonin and leptin secretion rhythms. To test this hypothesis, six different groups were used (Nâ=â6 rats per group): control (12 h/12h light:dark); exposure to permanent illumination (24 h light); exposure to darkness (22 h dark); injected with adriamycin, 12h/12h light:dark; injected with adriamycin + exposure to permanent illumination and injected with adriamycin + exposure to darkness (22 h dark). The different photoperiods were begun two weeks prior to medication and were maintained up to the day of the animal's sacrifice, ten days after medication. The following parameters were analysed: i) weight evolution; ii) in plasma: urea, creatinine, uric acid, total proteins, albumen, lactate dehydrogenase, creatinine-quinase, aspartate aminotransferase, alanine aminotransferase and total cholesterol; iii) in urine: urea, creatinine, total proteins and microalbumen; iv) biomarkers of oxidative damage in kidneys, heart, liver and brain: lipoperoxides, total glutathione, reduced glutathione, catalase, glutathione peroxidase, glutathione reductase and glutathione transferase; v) melatonin (pineal gland tissue and plasma) and leptin (plasma). From the results obtained it was concluded that the administration of adriamycin generated oxidative stress in renal, cerebral, hepatic and cardiac tissue. Additionally, in the healthy animal, but of a lesser relevance in the adriamycin animal, permanent light worsened the oxidative stress, whereas darkness improved it. This could be related to the circadian rhythm of the inverse release shown by melatonin and leptin, accentuating the release of melatonin in the darkness phase and that of leptin in the light phase. The correlation between melatonin and leptin in the healthy animal seemed to confirm the relationship between both variables and their influence on oxidative damage biomarkers.
Assuntos
Antibióticos Antineoplásicos , Doxorrubicina , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/complicações , Nefropatias/induzido quimicamente , Estresse Oxidativo , Fotoperíodo , Animais , Modelos Animais de Doenças , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Leptina/metabolismo , Masculino , Melatonina/metabolismo , Néfrons/efeitos dos fármacos , Néfrons/metabolismo , Néfrons/patologia , Ratos WistarRESUMO
HYPOTHESIS: Immune response may influence hearing outcome in Ménière's disease (MD). BACKGROUND: Major histocompatibility complex class I chain-related A (MICA) encodes a highly polymorphic stress-inducible protein, which interacts with NKGD2 receptor on the surface of NK, γδ T cells and T CD8 lymphocytes. We investigated the association of MICA gene with hearing outcome in MD and its linkage disequilibrium (LD) with human leukocyte antigen (HLA)-B. METHODS: MICA short tandem repeat polymorphism (MICA-STR) was genotyped using a polymerase chain reaction-based method in a total of 302 Spanish patients with MD and 420 healthy controls. Genotyping of HLA-B was performed using polymerase chain reaction and detected with reverse sequence-specific oligonucleotide probe system in 292 patients and 1,014 controls. RESULTS: Hearing loss was associated with the duration of MD (p = 0.001). We found that MICA*A5 alelle was significantly associated in the Mediterranean set (Pc = 0.04, odds ratio = 0.51 [95% confidence interval, 0.30-0.84]), but this finding was not replicated in the Galicia population. However, median time to develop hearing loss greater than 40 dB was 16 years (95% confidence interval, 9-23) for patients with the MICA*A.4 allele and 10 years (95% confidence interval, 9-11) for patients with another MICA-STR allele (log-rank test, p = 0.0038). We did not find statistical differences in the distribution of B locus between the MD and the control group. In the LD analysis, MICA*A5.1-HLA-B*07 (8.8%), MICA*A6-HLA-B*44 (8.3%), and MICA*A6-HLA-B*51 (8.3%) were the most common haplotypes, and the stronger LD was found for haplotypes MICA*A.4-HLA-B*18 (r2 = 0.41) and MICA*A.4-HLA-B*27(r2 = 0.29). CONCLUSION: The allelic variant MICA*A.4 is significantly associated with slower progression of hearing loss in patients with MD. This suggests that the immune response influence hearing level in MD.
Assuntos
Perda Auditiva/etiologia , Perda Auditiva/genética , Antígenos de Histocompatibilidade Classe I/genética , Doença de Meniere/complicações , Doença de Meniere/genética , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , DNA/genética , Primers do DNA , Progressão da Doença , Éxons/genética , Feminino , Estudos de Associação Genética , Genótipo , Antígenos HLA/genética , Perda Auditiva/epidemiologia , Heterozigoto , Humanos , Estimativa de Kaplan-Meier , Desequilíbrio de Ligação , Masculino , Doença de Meniere/epidemiologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Recidiva , Espanha/epidemiologia , Análise de Sobrevida , Adulto JovemRESUMO
Hearing loss in Ménière's disease (MD) is associated with loss of spiral ganglion neurons and hair cells. In a guinea pig model of endolymphatic hydrops, nitric oxide synthases (NOS) and oxidative stress mediate loss of spiral ganglion neurons. To test the hypothesis that functional variants of NOS1 and NOS2A are associated with MD, we genotyped three functional variants of NOS1 (rs41279104, rs2682826, and a cytosine-adenosine microsatellite repeat in exon 1f) and the CCTTT repeat in the promoter of NOS2A gene (rs3833912) in two independent MD sets (273 patients in total) and 550 controls. A third cohort of American patients was genotyped as replication cohort for the CCTTT repeat. Neither allele nor genotype frequencies of rs41279104 and rs2682826 were associated with MD, although longer alleles of the cytosine-adenosine microsatellite repeat were marginally significant (corrected p = 0.05) in the Mediterranean cohort but not in a second Galicia cohort. Shorter numbers of the CCTTT repeat in NOS2A were significantly more frequent in Galicia controls (OR = 0.37 [CI, 0.18-0.76], corrected p = 0.04), but this finding could not be replicated in Mediterranean or American case-control populations. Meta-analysis did not support an association between CCTTT repeats and risk for MD. Severe hearing loss (>75 dB) was also not associated with any functional variants studied. Functional variants of NOS1 and NOS2A do not confer susceptibility for MD.
Assuntos
Variação Genética , Perda Auditiva Neurossensorial/genética , Doença de Meniere/genética , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo I/genética , População Branca/genética , Sequência de Bases , Sítios de Ligação/genética , Frequência do Gene , Genótipo , Perda Auditiva Neurossensorial/patologia , Humanos , Doença de Meniere/patologia , Repetições de Microssatélites/genética , Dados de Sequência Molecular , Regiões Promotoras Genéticas/genética , Análise de Sequência de DNA , Espanha , Estados UnidosRESUMO
OBJECTIVES/HYPOTHESIS: Bilateral Meniere's disease (BMD) is a severe disease that usually results in bilateral severe or profound sensorineural hearing loss and chronic disequilibrium with loss of vestibular function. We examined single nucleotide polymorphisms (SNPs) in the PTPN22 and CTLA4 genes in Caucasian patients with BMD to assess the possible association between these polymorphism and the predisposition and clinical expression of this disease. STUDY DESIGN: A case control study. METHODS: The functional protein tyrosine phosphatase type 22 (PTPN22) SNP (rs2476601, 1858C/T) and CTLA4 SNP (rs231775, 49A/G) were analyzed in 52 patients with BMD and 348 healthy controls by a TaqMan 5' allelic discrimination assay. Data were analyzed by a chi(2) test with Fisher exact test. RESULTS: No association was found between the +49A/G CTLA4 genotype and BMD patients. However, the heterozygote PTPN22 1858C/T genotype was present at a significantly higher frequency in BMD patients than in controls (odds ratio = 2.25, 95% confidence interval: 1.09-4.62; P = .04). CONCLUSIONS: These results suggest that the PTPN22 1858C/T genotype may confer differential susceptibility to BMD in the Spanish population and support an autoimmune etiology for BMD.
Assuntos
Doença de Meniere/genética , Polimorfismo Genético , Proteínas Tirosina Fosfatases/genética , Autoimunidade , Feminino , Genótipo , Humanos , Masculino , Doença de Meniere/epidemiologia , Doença de Meniere/imunologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Espanha/epidemiologiaRESUMO
CONCLUSION: The longer alleles (CA)17-20 of the promoter region of PARP-1 gene may confer some protection against bilateral Meniere's disease (BMD). OBJECTIVE: To analyze microsatellite (CA)(n) polymorphisms in the promoter region of PARP-1 gene and seek out risk and protective variants for BMD. SUBJECTS AND METHODS: Eighty patients from two ethnically defined groups with definite BMD, according to the diagnostic scale of the American Academy of Otolaryngology Head and Neck Surgery, were compared with a group of 371 normal controls from the same origin in a prospective multicenter study. We developed a specific amplification protocol to determine the PARP1-promotor CA microsatellite polymorphisms. RESULTS: We found that the longer alleles (CA)17-20 had a very low frequency in BMD (2/160, 1.3%, OR=7.33 (1.77-30.37, 95% CI), corrected p=0.012), suggesting that it may confer some protection against BMD.