Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
1.
Pharmacogenomics ; 21(5): 317-323, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32308134

RESUMO

Aim: We examined associations of eight SNPs in/near seven candidate genes with glycemic response to 6 month treatment with DPP4 inhibitors. Patients & methods: 206 patients with type 2 diabetes (116 men and 90 women) were treated with sitagliptin or vildagliptin (both 100 mg/day) in combination with metformin or metformin/sulphonylurea over 6 months, and the reduction in glycated hemoglobin (HbA1c) was measured. Results: Rs6923761 in GLP1R was significantly associated with a reduction in HbA1c (adjusted p = 0.006). Homozygotes for the minor A allele had smaller reduction in HbA1c by 0.4% (4 mmol/mol) than the G allele carriers (p = 0.016). Conclusion: The missense variant rs6923761 in the GLP1R gene was associated with a smaller glycemic response to 6 month gliptin therapy in diabetic patients of central European origin.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Metformina , Masculino , Humanos , Feminino , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Vildagliptina/uso terapêutico , Alelos
2.
Artigo em Inglês | MEDLINE | ID: mdl-28422192

RESUMO

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is the most common orofacial birth defect with an aetiology involving both genetic and environmental factors. Genome-wide association studies (GWAS) have identified several genomic susceptibility regions for nsCL/P. In the present study, the three well established single nucleotide polymorphisms (SNPs) identified by GWAS (rs987525 at 8q24, rs7078160 at 10q25, and rs227731 at 17q22 loci) and one SNP identified by candidate gene study (rs642961 in IRF6 gene at 1q32 locus) were analysed for an association with nsCL/P in Slovak population. METHODS: Nucleotide variants were genotyped in 165 nsCL/P patients and 326 unaffected controls. All variants of interest were genotyped using high-resolution melting analysis after real-time PCR. RESULTS: We found significant differences between patient and control groups with respect to the allele and genotype frequencies for the SNPs at the 1q32, 8q24, and 17q22 loci. SNP at the 10q25 locus showed a trend toward association with nsCL/P risk. CONCLUSIONS: The results suggest that SNPs at the 1q32, 8q24 and 17q22 loci may contribute to the nsCL/P risk in Slovak population.


Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Predisposição Genética para Doença , República Tcheca , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
3.
Int J Endocrinol ; 2013: 374858, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23509454

RESUMO

Previous studies showed associations between variants in TCF7L2 gene and the therapeutic response to sulfonylureas. All sulfonylureas stimulate insulin secretion by the closure of ATP-sensitive potassium (KATP) channel. The aim of the present study was to compare TCF7L2 genotype specific effect of gliclazide binding to KATP channel A-site (Group 1) with sulfonylureas binding to AB-site (Group 2). A total of 101 patients were treated with sulfonylureas for 6 months as an add-on therapy to the previous metformin treatment. TCF7L2 rs7903146 C/T genotype was identified by real-time PCR with subsequent melting curve analysis. Analyses using the dominant genetic model showed significantly higher effect of gliclazide in the CC genotype group in comparison with combined CT + TT genotype group (1.32 ± 0.15% versus 0.73 ± 0.11%, P (adj) = 0.005). No significant difference in ΔHbA1c between the patients with CC genotype and the T-allele carriers was observed in Group 2. In the multivariate analysis, only the TCF7L2 genotype (P = 0.006) and the baseline HbA1c (P < 0.001) were significant predictors of ΔHbA1c. After introducing an interaction term between the TCF7L2 genotype and the sulfonylurea type into multivariate model, the interaction became a significant predictor (P = 0.023) of ΔHbA1c. The results indicate significantly higher difference in ΔHbA1c among the TCF7L2 genotypes in patients treated with gliclazide than in patients treated with glimepiride, glibenclamide, or glipizide.

4.
Mol Cell Probes ; 26(4): 159-63, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22521237

RESUMO

BACKGROUND & AIM: Hepatitis C is a liver disease caused by the hepatitis C virus. Interferon and ribavirin combination therapy has been a standard treatment of chronic hepatitis C. But only about 50% of patients have positive response to treatment and achieve so called sustained virological response. Recent studies indicate association of several single nucleotide polymorphisms near IL28B gene and response of hepatitis C patients to combined interferon/ribavirin treatment. In this study, rapid, specific and cost-effective small amplicon genotyping method for the two clinically important polymorphisms, rs12979860 C > T and rs8099917 T > G, near the IL28B gene is described. METHODS: The distribution of genotypes of 181 HCV-uninfected Slovak Caucasians was analyzed using this novel method, based on a real-time melting analysis of the small amplicon. RESULTS AND CONCLUSIONS: The frequency of wild-type (TT) homozygotes for rs8099917 was 66.30%, frequency of heterozygotes (TG) was 30.94% and we found only 2.76% subjects homozygous for risk G allele (allelic frequencies: T = 81.77%, G = 18.23%) were found. The frequency of wild-type genotype (CC) for rs12979860 was 49.72%, frequencies of heterozygous (CT) and risk-allele homozygous genotypes (TT) were 39.78% and 10.50%, respectively (allele frequencies: C = 69.61%, T = 30.39%). Statistically significant differences in the distribution of the alleles between the men and the women were not found. The novel method developed in our laboratory proved to be simple and highly customizable.


Assuntos
Hepatite C/tratamento farmacológico , Hepatite C/genética , Interleucinas/genética , Adulto , Idoso , Alelos , Feminino , Testes Genéticos , Genótipo , Hepatite C/metabolismo , Heterozigoto , Homozigoto , Humanos , Interferons , Interleucinas/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
5.
Eur J Intern Med ; 23(3): 245-9, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22385882

RESUMO

AIMS: Potassium inwardly rectifier 6.2 subunit (Kir6.2) of the ATP-sensitive potassium (K(ATP)) channel encoded by KCNJ11 gene is a therapeutical target for sulfonylureas. KCNJ11 E23K polymorphism was associated with type 2 diabetes in genetic association studies. The aim of the present pharmacogenetic study was to examine the effect of sulfonylurea treatment on glycemic control in relationship to KCNJ11 E23K variant. PATIENTS AND METHODS: One hundred and one patients with type 2 diabetes who failed to achieve HbA1c<7% on previous metformin monotherapy were included to the study. Sulfonylurea drug was given in addition to metformin. The main outcome of the study was reduction in HbA1c level (ΔHbA1c) after 6-month sulfonylurea therapy. KCNJ11 genotypes were determined by real-time PCR with melting curve analysis. RESULTS: After 6-month treatment, KCNJ11 K-allele carriers had higher decrease in HbA1c compared with EE homozygotes in the dominant genetic model (1.04±0.10 vs. 0.79±0.12%, p=0.036). In the log-additive model, greater mean reduction in HbA1c by 0.16% (95% CI 0.01-0.32, p=0.038) per each K-allele was observed. The relationship of treatment response with KCNJ11 genotype was also significant in the biggest subgroup of patients treated with gliclazide (n=55). CONCLUSIONS: Carriers of the KCNJ11 K-allele have better therapeutic response to gliclazide. This observation might help to identify patients who will have the highest benefit from sulfonylurea treatment.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Resistência a Medicamentos/genética , Hipoglicemiantes/uso terapêutico , Canais de Potássio Corretores do Fluxo de Internalização/genética , Compostos de Sulfonilureia/uso terapêutico , Adulto , Idoso , Estudos de Coortes , Quimioterapia Combinada , Feminino , Variação Genética , Genótipo , Gliclazida/uso terapêutico , Humanos , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Farmacogenética , Polimorfismo Genético/genética
6.
Med Oncol ; 29(2): 1173-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21476145

RESUMO

Follicular lymphoma (FL) is one of the most common Non-Hodgkin lymphoma (NHL) subtype. Only small number of studies concerning NHL and DNA reparation gene polymorphisms has been performed so far. Hence, we have assessed the effect of 4 selected polymorphisms with possible influence on risk of FL development in a case-control study in Slovak population. We have genotyped polymorphisms in the RAG1 (K820R), LIG4 (T9I), BRCA2 (N372H), and WRN (V114I) genes in 108 patients with histologically proven FL diagnosis and 127 healthy controls. For discrimination between the allelic variants, we have established the genotyping by real-time melting analysis of an unlabeled probe. The most notable finding was related to polymorphism N372H in the BRCA2 gene. Compared with the wild-type genotype (NN), the homozygous variant genotype (HH) was associated with an increased FL risk (OR = 2.91, 95% CI: 0.96-8.81), although on the borderline of statistical significance (P = 0.050). However, after stratification by gender and age, the FL risk was significantly increased in men with variant-containing genotypes (OR = 2.79, 95% CI: 1.20-6.45) and even severalfold significantly increased among men with homozygous variant BRCA2 genotype (OR = 21.18, 95% CI: 2.46-182.2). No significant associations with FL risk were identified for other polymorphisms.


Assuntos
Proteína BRCA2/genética , Predisposição Genética para Doença , Linfoma Folicular/epidemiologia , Linfoma Folicular/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , DNA/genética , DNA Ligase Dependente de ATP , DNA Ligases/genética , Exodesoxirribonucleases/genética , Feminino , Genótipo , Proteínas de Homeodomínio/genética , Humanos , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , RecQ Helicases/genética , Fatores de Risco , Eslováquia/epidemiologia , Helicase da Síndrome de Werner , Adulto Jovem
7.
Med Sci Monit ; 17(7): CR392-6, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21709633

RESUMO

BACKGROUND: We aimed to analyse quantitative effects of treatment with sulphonylurea in addition to metformin on parameters of glycemic control in relation to KCNQ1 genotypes, and to identify factors predictive for the response to sulphonylurea treatment. MATERIAL/METHODS: Effect of 6-month sulphonylurea therapy in addition to metformin on glycemic control according to KCNQ1 genotypes was evaluated in 87 patients with type 2 diabetes who failed to achieve glycemic control on metformin monotherapy. KCNQ1 rs163184 (T>G) polymorphism was determined by real-time PCR with melting analysis of unlabeled probe. RESULTS: The reduction in fasting plasma glucose (ΔFPG) after 6-month sulphonylurea therapy significantly differed among 3 KCNQ1 genotype groups (ANOVA, p=0.017). In a recessive genetic model, carriers of the T-allele (TT+TG) achieved significantly lower FPG levels in comparison with patients with the GG genotype (6.95 ± 0.13 vs. 7.50 ± 0.21 mmol/L, p=0.033). Consequently, ΔFPG was significantly higher in the TT+TG group compared to the GG group (1.58 ± 0.13 vs. 1.04 ± 0.18 mmol/L, p=0.016). In multiple linear regression analysis KCNQ1 genotype (p=0.016) and baseline FPG (p<0.001) were the only significant independent predictors of ΔFPG (R2=0.48). CONCLUSIONS: Our results suggest that the magnitude of FPG reduction after 6-month sulphonylurea treatment in addition to metformin in patients with type 2 diabetes is related to the variation in KCNQ1. The FPG response to sulphonylureas was significantly lower in carriers of the risk GG genotype.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Canal de Potássio KCNQ1/genética , Compostos de Sulfonilureia/uso terapêutico , Análise de Variância , Glicemia/análise , Primers do DNA/genética , Genótipo , Humanos , Canal de Potássio KCNQ1/metabolismo , Modelos Lineares , Metformina/uso terapêutico , Farmacogenética , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único/genética
8.
Mol Biol Rep ; 38(2): 1287-93, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20568013

RESUMO

N-acetyltransferase 2 (NAT2) is phase II enzyme with major roles in catalyzing the detoxification of aromatic amines, which are known risk factors for bladder cancer, and are ubiquitously present in the environment. We assessed the association between common polymorphisms in NAT2 gene and the risk of bladder cancer in 90 Slovak patients and 274 ethnicity-matched healthy controls. Effect modifications by smoking, age and gender were also evaluated. Overall, NAT2 slow acetylation was associated with significantly increased risk of bladder cancer (OR = 1.90; 95% CI, 1.15-3.16). In stratified analyses by age and gender, the elevated risk conferred by slow acetylator genotype was evident in older individuals (OR = 3.55; 95% CI, 1.77-7.35) and males (OR = 4.65; 95% CI, 1.68-16.10), with further increasing in NAT2*5B/*6A genotype carriers. Smoking was confirmed to be important risk factor, moreover, the risk was markedly increased in smokers with NAT2 slow acetylator genotype, and NAT2*5B/*6A carriers especially. In summary, these findings are consistent with previous literature suggesting that individual susceptibility to bladder cancer may be modulated by NAT2 polymorphisms, particularly in interaction with relevant environmental exposures such as smoking.


Assuntos
Arilamina N-Acetiltransferase/genética , Neoplasias da Bexiga Urinária/genética , Aminas/química , Etnicidade , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Fatores de Risco , Fatores Sexuais , Eslováquia , Fumar , Neoplasias da Bexiga Urinária/etnologia
9.
Med Sci Monit ; 14(8): CR392-8, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18667995

RESUMO

BACKGROUND: The role of the beta2-adrenergic receptor (ADRB2) genotype in patients with chronic obstructive pulmonary disease (COPD) is unclear. In patients with acute exacerbations of COPD (AECOPD), we assessed the role of ADRB2 haplotypes in morning lung function and in the bronchodilator response to salbutamol. MATERIAL/METHODS: In 107 patients with AECOPD, polymorphisms in the amino acid position 16 (Arg16/Gly16) and 27 (Gln27/Glu27) of the ADRB2 gene were assessed by allele-specific polymerase chain reaction, identifying 31 subjects with the Gly16/Glu27-negative and 76 with the Gly16/Glu27-positive ADRB2 haplotype. Pulmonary function and bronchodilator response to salbutamol were assessed using bodyplethysmography. RESULTS: Forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) were significantly higher in the Gly16/Glu27-negative compared to the Gly16/Glu27-positive haplotype group at baseline (49.7+/-2.9% vs 42.4+/-1.8% predicted, P=0.037; 44.0+/-2.2% vs 36.4+/-1.6% predicted, P=0.008, respectively). FEV1, PEF, and forced vital capacity (FVC) increased from baseline to after salbutamol treatment in both the Gly16/Glu27-negative and the Gly16/Glu27-positive ADRB2 haplotype groups (P<0.001 for all comparisons). Values for FEV1 and PEF after administration of the bronchodilator were significantly higher in the Gly16/Glu27-negative haplotype group compared with the Gly16/Glu27-positive haplotype group (P=0.030 and P=0.034, respectively). No differences were observed in DeltaFEV1, DeltaPEF, or DeltaFVC after bronchodilation between the 2 ADRB2 haplotype groups (12.2+/-1.8% vs 14.5+/-1.5% predicted, P=0.393; 12.2+/-3.3% vs 20.8+/-3.2% predicted, P=0.117; 9.1+/-2.3% vs 10.4+/-1.9% predicted, P=0.707, respectively). CONCLUSIONS: The present findings suggest that the ADBR2 gene haplotypes may affect the severity of obstructive ventilatory impairment but not the immediate response to salbutamol during AECOPD.


Assuntos
Albuterol/uso terapêutico , Broncodilatadores/uso terapêutico , Haplótipos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/genética , Receptores Adrenérgicos beta 2/genética , Adulto , Idoso , Códon/genética , Demografia , Feminino , Ácido Glutâmico/genética , Glicina/genética , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória
10.
Croat Med J ; 49(2): 182-91, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18461673

RESUMO

AIM: To determine the risk of chronic obstructive pulmonary disease (COPD) associated with polymorphisms in the glutathione S-transferase (GST) M1, GST T1, and microsomal epoxide hydrolase (EPHX1) genes in a cohort of Slovak population. METHODS: Two hundred and seventeen patients with the diagnosis of COPD and 160 control subjects were enrolled in the study. Blood samples were collected from all subjects and the DNA from peripheral blood lymphocytes was used for subsequent genotyping assays, using polymerase chain reaction and restriction fragment-length polymorphism methods. RESULTS: In an unadjusted model, an increased risk for COPD was observed in subjects with EPHX1 His113-His113 genotype (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.20-4.69; P=0.008), compared with the carriers of the Tyr113 allele. However, after the adjustments for age, sex, and smoking status, the risk was not significant (adjusted OR, 1.79; 95% CI, 0.91-3.53; P=0.093). In a combined analysis of gene polymorphisms, the genotype combination EPHX1 His113-His113/GSTM1 null significantly increased the risk of COPD in both, unadjusted (OR, 5.08; 95% CI, 1.70-20.43; P=0.001) and adjusted model (OR, 4.87; 95% CI, 1.57-15.13; P=0.006). CONCLUSION: Although none of the tested gene polymorphisms was significantly related to an increased risk of COPD alone, our results suggest that the homozygous exon 3 mutant variant of EPHX1 gene in the combination with GSTM1 null genotype is a significant predictor of increased susceptibility to COPD in the Slovak population. The findings of the present study emphasize the importance of detoxifying and antioxidant pathways in the pathogenesis of COPD.


Assuntos
Epóxido Hidrolases/genética , Glutationa Transferase/genética , Polimorfismo Genético , Doença Pulmonar Obstrutiva Crônica/enzimologia , Estudos de Casos e Controles , Epóxido Hidrolases/metabolismo , Feminino , Genótipo , Glutationa Transferase/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores de Risco , Eslováquia/epidemiologia
11.
Mutat Res ; 620(1-2): 41-8, 2007 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-17391715

RESUMO

The aim of this study was to determine the influence of carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) in complex mixtures in ambient air on DNA damage (chromosomal aberrations) in occupationally exposed subjects measured as percent of aberrant cells (% AB.C.). There were in total 203 exposed subjects and 150 respective controls in the whole project, allocated in three different European cities - Kosice (Slovakia), Prague (Czech Republic) and Sofia (Bulgaria). The studied population from Kosice (Slovakia) consisted of 106 subjects. From these 51 were exposed policemen and 55 were controls. The Czech population comprised 52 exposed policemen and 50 controls. In Bulgaria, there were two equally numerous exposed groups: 50 policemen and 50 professional bus drivers together with 45 controls. According to personal monitoring, policemen and bus drivers in the Bulgarian capital Sofia were exposed to the highest levels of c-PAHs amongst the exposed subject groups in the cities (45.3+/-25.9ng/m(3) in policemen resp. 36.1+/-31.6ng/m(3) in bus drivers in Sofia, 26.8+/-39.8ng/m(3) for policemen in Kosice and 11.9+/-11.2ng/m(3) for policemen in Prague), compared to the respective controls (24.9+/-17.7ng/m(3) for controls in Sofia, 7.9+/-3.8ng/m(3) for controls in Kosice and 6.2+/-3.6ng/m(3) for controls in Prague). We observed the following frequency of % AB.C. scored by conventional method: 2.60+/-2.64 in exposed policemen and 2.14+/-1.61 in controls in Kosice (p=n.s.); 2.33+/-1.53 in exposed policemen and 1.94+/-1.28 in controls in Prague (p=n.s.); 3.04+/-1.64 in exposed policemen, respectively, 3.60+/-1.63 in exposed bus drivers and 1.79+/-0.77 in the control group in Sofia (p<0.05, respectively, p<0.05). According to data from multiple regression analysis, and group comparison of smokers versus nonsmokers in Sofia also cigarette smoking (p=0.055) and the age (p=0.020) seem to play an important role within the aberrant cell formation in addition to the occupational c-PAHs exposure (p=0.000). Smoking status was the modifying factor for % AB.C. in Kosice (p=0.020) after multiple regression approach was employed. In summary, we can say that subjects occupationally exposed to higher levels of c-PAHs in ambient air in Sofia are at greater genotoxic risk compared to those working indoors.


Assuntos
Poluentes Atmosféricos/toxicidade , Carcinógenos Ambientais/toxicidade , Aberrações Cromossômicas , Exposição Ocupacional , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Polícia
12.
Wien Klin Wochenschr ; 117(5-6): 210-4, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15875760

RESUMO

OBJECTIVE: The insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with an increased risk of cardiovascular diseases. In patients with primary pulmonary hypertension, the homozygous ACE DD genotype is more prevalent than the non-DD genotype. However, the relationship of ACE gene polymorphism to secondary pulmonary hypertension remains unclear, and ethnicity may be one of the factors that can modulate the effects of ACE genotypes reported in different studies. We hypothesized that in patients with chronic obstructive pulmonary disease (COPD) the presence of the D allele in the ACE gene polymorphism is associated with increased pulmonary artery pressure (Ppa). PATIENTS AND METHODS: Bodyplethysmography was used to assess lung function in 66 consecutive patients with COPD; pulmonary artery pressures were determined using echocardiography. ACE gene I/D polymorphism was identified with the polymerase chain reaction. 118 healthy persons served as the control group. All patients and controls were Caucasian. Genotype II was identified in 15 patients with COPD, genotype ID in 31 and genotype DD in 20. In the control group, genotype II was identified in 19 persons, genotype ID in 68 and genotype DD in 31. The distribution of ACE gene polymorphism did not differ between patients and the control group. RESULTS: In patients with COPD, no differences were seen between the three genotype groups in mean age, smoking history, hemoglobin concentrations or ventilometric or blood gas variables. Both systolic and mean Ppa differed significantly between the II, ID and DD groups (Systolic Ppa: 24.4 +/- 2.2 versus 31.3 +/- 2.5 and 36.7 +/- 3.9 mm Hg, respectively, ANOVA, p < 0.05; Mean Ppa: 13.0 +/- 1.5 versus 17.5 +/- 1.4 and 21.2 +/- 2.8 mm Hg, respectively, ANOVA, p < 0.05). In multiple linear regression analysis, the I/D ACE gene polymorphism (p < 0.05), SaO2 (p < 0.05) and the duration of COPD (p < 0.02) were independent predictors of systolic and mean Ppa. CONCLUSION: The results of the study suggest that I/D ACE gene polymorphism is linked to pulmonary artery pressure in Caucasian patients with COPD.


Assuntos
Predisposição Genética para Doença/epidemiologia , Testes Genéticos/métodos , Hipertensão Pulmonar/enzimologia , Hipertensão Pulmonar/epidemiologia , Peptidil Dipeptidase A/genética , Doença Pulmonar Obstrutiva Crônica/enzimologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Medição de Risco/métodos , Idoso , Biomarcadores Tumorais/genética , Pressão Sanguínea , Comorbidade , Estudos Transversais , Análise Mutacional de DNA/métodos , Feminino , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/genética , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/sangue , Polimorfismo Genético , Artéria Pulmonar/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/genética , Fatores de Risco , Eslováquia/epidemiologia
13.
Wien Klin Wochenschr ; 116(4): 131-4, 2004 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-15038404

RESUMO

OBJECTIVE: Oxidative stress contributes to the development of both lung cancer and chronic obstructive pulmonary disease (COPD). Antioxidative enzymes may protect against such damage. We hypothesized that genetic variations in glutathione S-transferase M1 and/or T1 genes (GSTM1 and GSTT1, respectively) may influence susceptibility to COPD in patients with non-small-cell lung cancer. PATIENTS AND METHODS: The polymorphisms in GSTM1 and GSTT1 genes were examined in 110 patients (age: 63+/-1 years) with newly diagnosed non-small-cell lung cancer using the polymerase chain reaction. Respiratory function was assessed by bodyplethysmography. RESULTS: In the GSTM1 null (-/-) genotype, both FEV1 and FEV1/FVC were significantly lower than in the GSTM1 plus genotype (GSTM1 -/+ or +/+) (75.8+/-2.5 versus 86.6+/-3.6%, p<0.02; 69.1+/-1.6 versus 77.0+/-2.4, p<0.01, respectively). Among the patients with GSTM1 null genotype, 49% suffered from COPD as opposed to 21% of patients with GSTM1 plus genotype. In contrast, no differences were seen in FEV1 or FEV1/FVC when comparing patients with GSTT1 null genotype and GSTT1 plus genotype (81.4+/-4.9 versus 79.3+/-2.3, p=NS; 71.1+/-2.9 versus 72.2+/-1.6, p=NS). Multiple stepwise regression analysis identified the GSTM1 genotype (p<0.02) as a significant independent predictor of FEV1 in this group of patients. CONCLUSION: The present study suggests that in patients with non-small-cell lung cancer the presence of at least one active allele in GSTM1 has a protective effect against the development of COPD.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Glutationa Transferase/genética , Neoplasias Pulmonares/genética , Polimorfismo Genético/genética , Doença Pulmonar Obstrutiva Crônica/genética , Alelos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Feminino , Volume Expiratório Forçado/fisiologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Predisposição Genética para Doença/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Reação em Cadeia da Polimerase , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fatores de Risco , Fumar/efeitos adversos , Capacidade Vital/fisiologia
14.
Carcinogenesis ; 24(5): 875-82, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12771031

RESUMO

Polymorphisms for genes encoding the metabolic enzymes cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) might contribute to the variability in individual susceptibility to lung cancer. The role of CYP1A1 and GSTM1 in lung carcinogenesis might be more important at low levels of exposure to carcinogens. Non-smokers represent a population at low exposure, however, they are often overlooked because of the small number of cases. We therefore conducted a pooled analysis of 14 case-control studies on lung cancer in Caucasian non-smokers with comparable information on genetic polymorphisms included in the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens. We pooled the raw data from a total of 302 cases and 1631 controls with random effects models. We also evaluated the possibility of inclusion bias and conducted influence analyses. The odds ratio (OR) of lung cancer for the variant CYP1A1 Ile(462)Val polymorphism (Ile/Val, Val/Val) was 2.99 [95% confidence interval (95%CI) 1.51-5.91]; this effect was stronger on lung adenocarcinoma (OR 4.85, 95%CI 2.03-11.6). After excluding outlying or imprecise studies, we did not observe a significant effect of the CYP1A1 MspI (T(3801)C) polymorphism or GSTM1 null genotype (OR 1.20, 95%CI 0.89-1.63). Furthermore, our analyses suggested a combined effect of the CYP1A1 Ile(462)Val polymorphism and GSTM1 null genotype. The OR for the combination of the CYP1A1 Ile(462)Val variant and GSTM1 null genotype was 4.67 (95%CI 2.00-10.9) compared with the concurrent presence of the CYP1A1 wild-type and GSTM1 non-null genotype. We did not observe a modification of the effect of the GSTM1 null genotype according to exposure to environmental tobacco smoke and urban/rural residence. Our study therefore suggests that the CYP1A1 Ile(462)Val variant allele might play a role in lung carcinogenesis among non-smokers, possibly in combination with the GSTM1 null genotype.


Assuntos
Citocromo P-450 CYP1A1/genética , Glutationa Transferase/genética , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Polimorfismo Genético/genética , Fumar , População Branca , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Frequência do Gene , Genótipo , Humanos , Neoplasias Pulmonares/enzimologia , Razão de Chances , Fatores de Risco , Estados Unidos/epidemiologia
15.
Wien Klin Wochenschr ; 115(1-2): 36-40, 2003 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-12658909

RESUMO

AIMS: To evaluate the influence of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on lipid levels in patients with Type 2 diabetes. PATIENTS AND METHODS: 109 patients with Type 2 diabetes were included. The patients were not on any lipid-lowering treatment. The groups with different ACE genotypes had similar ages, sex distributions, body mass indices, systolic blood pressures and indices of glycaemic control. ACE gene I/D polymorphism was determined using polymerase chain reaction. RESULTS: The mean apolipoprotein B (apoB) level was significantly higher in the group of DD homozygotes compared with the subjects with at least one insertion allele (DD: 1.21 +/- 0.25 g/l vs. ID + II: 1.04 +/- 0.27 g/l; P = 0.007). Significant correlations between glycated haemoglobin (HbA1c) and both apoB and cholesterol levels were found (r = 0.27; P < 0.01). For the apoB, this correlation was highly significant in the DD-genotype subgroup (r = 0.54; P < 0.01), and was not significant in the subgroup of patients with genotypes ID or II. In the multivariate analysis, HbA1c and the interaction of genotype DD with HbA1c were significant independent predictors of apoB (r2 = 0.17) and cholesterol levels. CONCLUSION: The present study showed that the interaction between the DD genotype of angiotensin-converting enzyme and chronic hyperglycaemia (expressed by HbA1c level) is related to higher plasma levels of atherogenic lipoproteins, such as apoB and cholesterol, in patients with Type 2 diabetes.


Assuntos
Glicemia/metabolismo , Doença da Artéria Coronariana/genética , Diabetes Mellitus Tipo 2/genética , Genótipo , Hemoglobinas Glicadas/metabolismo , Lipoproteínas/sangue , Peptidil Dipeptidase A/genética , Idoso , Apolipoproteínas B/sangue , Colesterol/sangue , Doença da Artéria Coronariana/sangue , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/genética , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/sangue , Fatores de Risco
16.
Wien Klin Wochenschr ; 115(23): 835-9, 2003 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-14740347

RESUMO

AIMS: Increased fibrinogen level is considered an important atherosclerosis risk factor. Patients with type 2 diabetes frequently have increased fibrinogen levels. The aim of the present study was to examine the effect of angiotensin-converting enzyme (ACE) gene polymorphism and the effects of the diabetic environment on plasma fibrinogen in type 2 diabetes. PATIENTS AND METHODS: The study group included 125 patients with type 2 diabetes (40 men, 85 women). The average age of patients was 62 +/- 10 years. Fibrinogen concentration was determined with the thrombin coagulation test. ACE insertion/deletion (I/D) polymorphism was detected using polymerase chain reaction (PCR) assay. RESULTS: II homozygotes (n = 17) had the highest mean fibrinogen levels, ID heterozygotes (n = 75) had medium levels and DD homozygotes (n = 33) had the lowest (p = 0.054, ANOVA). II homozygotes also had significantly higher mean fibrinogen level than ID/DD carriers (4.3 +/- 1.7 vs. 3.5 +/- 1.3 g/l; p = 0.015). The indices of renal functions, i.e. albuminuria (r = 0.37; p < 0.0001) and serum creatinine (r = 0.22; p = 0.015), significantly correlated with fibrinogen levels. The correlation between albuminuria and fibrinogen was significant in the subgroups with genotypes II (r = 0.76; p = 0.001) and ID (r = 0.37, p = 0.002), whereas in the subgroup of DD homozygotes this relationship did not reach statistical significance. In the multivariate regression analysis with age, sex, BMI, creatinine, albuminuria and ACE genotype as independent variables, albuminuria was the only significant predictor of fibrinogen level (p < 0.0001). After interaction between the ACE genotype and albuminuria was included into multivariate analysis, the interaction became the only independent predictor of plasma fibrinogen level (p < 0.0001) in the model, and the model explained 25% of the plasma fibrinogen variance. CONCLUSION: ACE gene polymorphism is associated with plasma fibrinogen level in type 2 diabetes. This association is mediated by an interaction between ACE genotype and albuminuria. Diabetes patients with genotypes II or ID have increased plasma fibrinogen in the presence of albuminuria.


Assuntos
Albuminúria/etiologia , Diabetes Mellitus Tipo 2/genética , Fibrinogênio/análise , Genótipo , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Idoso , Análise de Variância , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Glicemia/análise , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/urina , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Perindopril/uso terapêutico , Reação em Cadeia da Polimerase , Fatores de Risco , Fumar
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...