RESUMO
OBJECTIVES: Only limited risk factors for ankylosing spondylitis (AS) have been identified to date. Therefore, we aimed to explore whether cardiovascular health (CVH) behaviours and factors are associated with the risk of developing AS. METHODS: Patients with incident AS were identified in cohorts from two ongoing prospective studies. Assessments were made of the association of AS with individual baseline cardiovascular health lifestyle behaviours (including smoking status, body mass index, physical activity and diet) and cardiovascular health factors (including total cholesterol levels, blood pressure levels and fasting plasma glucose levels), and with a cardiovascular health metric determined by the number of ideal behaviours and factors. Cox regression analysis was used for the estimation of hazard ratios (HRs) for AS. RESULTS: Among 124,303 participants, incident AS was identified in 53 individuals within the 8 years of follow-up. For participants with ideal physical activity (>80 min/week) the HR was 0.21 (95% CI 0.05-0.89) compared with participants without ideal physical activity after adjusting for potential confounders. No signi cant risk of developing AS was associated with baseline smoking, diet, body mass index, blood pressure, fasting blood glucose or total cholesterol status, nor did cardiovascular health metrics. CONCLUSIONS: Adherence to ideal physical activity may reduce the risk of developing AS.
Assuntos
Doenças Cardiovasculares , Espondilite Anquilosante , Glicemia , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Exercício Físico , Nível de Saúde , Humanos , Estudos Prospectivos , Fatores de Risco , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/epidemiologiaRESUMO
Visfatin, a pro-inflammatory cytokine predominantly released from leucocytes, is correlated with coronary artery disease (CAD). We have previously reported that the -1535C>T polymorphism (rs1330082), which located on the promoter region of visfatin, was associated with decreased risk of CAD. Here, we investigated the underlying mechanism by which this polymorphism affects the genetic susceptibility to CAD. The difference of the promoter activities between -1535T variant and -1535C allele was tested by luciferase reporter gene assay. The difference of transcription factor binding activities between T and C allele was evaluated by electrophoretic mobility shift assay. In reporter gene assay, we showed that the T variant had a significantly reduced transcriptional activity compared with the C allele. The T-variant significantly attenuated the promoter binding affinity to nuclear transcription factors and this effect became much obvious after treatment with TNF-α. Moreover, competition experiment revealed that the retarded complex formed by T-1535- or C-1535-probe binding to nuclear extracts was nearly completely inhibited by unlabeled activator protein-1 (AP-1) specific probe, indicating that AP-1 might be the target nuclear effector. Taken together, our data provided potential mechanistic link between the visfatin -1535C>T polymorphism and reduced CAD risk.
Assuntos
Doença da Artéria Coronariana/genética , Citocinas/genética , Nicotinamida Fosforribosiltransferase/genética , Polimorfismo de Nucleotídeo Único , Sítios de Ligação , Doença da Artéria Coronariana/metabolismo , Citocinas/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Genes Reporter , Predisposição Genética para Doença , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Interleucina-6/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Fator de Transcrição AP-1/metabolismo , Transcrição Gênica , Transfecção , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To study the association of fibrinogen(Fg) B beta -854G/A, -455G/A, -249C/T, -148C/T, 448G/A and Bcl-1G/A gene polymorphisms with factors affecting obesity, and the fibrinogen function such as plasma fibrinogen concentration and molecular reactivity. METHODS: One thousand and three hundred ninety-one subjects from Kailuan corporation were enrolled by medical examination and questionnaire survey, and were divided into normal weight, overweight and obese groups based on body mass index (BMI). Blood biochemistry, fibrinogen concentration, fibrin monomer polymerized velocity (FMPV), and FMPV/A(max) were measured. The gene polymorphisms of the six loci were detected by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequencies of Bcl-1A and its mutated genotype in the overweight group were significantly higher than that in the normal weight group (P< 0.01). In all the three groups, Fg concentration, FMPV, FMPV/A(max) in individuals with B beta -854 mutated genotype were significantly higher than those with wild type genotype (P< 0.01), and in the overweight group, FMPV/A(max) in those with B beta -455 mutated genotype, FMPV in those with B beta -249 mutated genotype, were higher than those with wild type genotype (P< 0.05). CONCLUSION: Individuals with Bcl-1A and its mutated genotype are susceptible to overweight. The B beta -455 and -249 mutated genotypes are accumulative genes for overweight by regulating the Fg function.
Assuntos
Fibrinogênio/genética , Obesidade/genética , Polimorfismo Genético , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Obesidade/prevenção & controle , Análise de RegressãoRESUMO
OBJECTIVE: To study the association of beta-fibrinogen(Fg) gene -148 C/T and 448 G/A polymorphisms, plasma Fg concentration, molecular reactivity and the type of cerebral infarction. METHODS: Gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The plasma Fg concentration and the molecular reactivity were also determined. RESULTS: The Fg concentration in MCI patients with T -148 allele was higher than that in PCI patients and controls. The MCI patients with A448 allele had higher Fg concentration, FMPV and FMPV/Amax when compared with controls, and had higher FMPV/Amax when compared with PCI patients. CONCLUSION: FgB beta -148 and 448 mutational genotypes have impact on Fg concentrationì and therefore increase the risk of MCI.
Assuntos
Infarto Cerebral/genética , Fibrinogênio/genética , Polimorfismo Genético , Idoso , Infarto Cerebral/sangue , Feminino , Fibrinogênio/metabolismo , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
OBJECTIVE: To explore the association between G614T single nuclear polymorphism (SNP) of the alpha-adducin gene and the antihypertensive effect of hydrochlorothiazide (HCTZ) in essential hypertensive (EH) patients. METHODS: Eight hundred twenty nine EH patients were given 12.5 mg HCTZ/d for six weeks. Alpha-adducin gene G614T SNP in the tenth exon was determined by PCR-RFLP in 754 patients with complete records. All the patients were grouped according to TT, GT and GG genotypes. RESULTS: After 6 weeks of HCTZ treatment, the decreases in DBP and MAP of patients carrying 614T allele of alpha-adducin were significantly greater than that of those carrying GG homozygotes (P < 0.05). The decreases in SBP and MAP were significantly greater in patients with the TT genotype as compared with GT or GG genotype (P < 0.05). The effective rate of BP fall by HCTZ was higher in patients with TT genotype than those with GT or GG genotype (P < 0.05). Multivariate stepwise regression analysis showed that the TT genotype and the baseline SBP were the two major predictors affecting the decrease in SBP. CONCLUSION: The present study suggests that the alpha-adducin G614T polymorphism is associated with the antihypertensive effect of HCTZ, which is more effective in patients with TT genotype.
Assuntos
Anti-Hipertensivos/uso terapêutico , Proteínas de Ligação a Calmodulina/genética , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Método Simples-Cego , Resultado do TratamentoRESUMO
OBJECTIVE: To observe the distribution character of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in Chinese population and its relationship with essential hypertension. METHODS: Polymerase chain reaction (PCR) technique was used to detect the angiotensin converting enzyme gene I/D polymorphism in 2966 subjects of Kailuan Coal Mine, and further restriction analysis was performed. RESULTS: The frequencies of ACE II, ID, DD genotypes in total study population were 41.5%, 38.4%, 20.1%, respectively. The DD genotypes in hypertensive group and that in control group were 18.9% and 21.0%, respectively. There was no significant difference between hypertensive group and control group (P>0.05). The same result was seen after stratification by age and gender in each group, respectively(P>0.05). The DD genotype and D allele showed a tendency to decrease with the increase of age (P<0.001). CONCLUSION: The above results suggested that essential hypertension was not associated with ACE I/D polymorphism. The distributions of ACE genotype and allele varied with age, and the subjects with the character of DD genotype were at higher risk of early death.
Assuntos
Hipertensão/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Frequência do Gene , Genótipo , Humanos , Hipertensão/enzimologia , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
Membranous nephropathy (MN) is a rare manifestation of IgG4-related disease. Interestingly, the significance of IgG4 has also been documented in idiopathic MN (IMN). Previous studies reported that urine IgG4/IgG ratios were significantly higher in IMN compared with other kinds of nephropathy, indicating that impairment of charge selectivity barrier seemed to be an obvious characteristic of IMN. Although high blood concentration of IgG4 is very common in IgG4-related MN, no study about the urine IgG4 has been described before. Here, we present a 55-year-old male with IgG4-related MN. Complete remission of proteinuria was promptly achieved by glucocorticoid treatment without immunosuppressant. Consistent with previous reports, the serum antibody against M-type phospholipase A2 receptor was negative. Surprisingly, although the blood concentration of IgG4/IgG reached as high as 36 %, the urine concentration of IgG4/IgG was only 5 %. The calculated ratio of the renal clearance of IgG4 to IgG of this patient (0.15) was obviously lower than that of five patients with IMN (0.53â¼0.81). We speculated that this phenomenon might be a clue of the different pathogenesis between IgG4-related MN and IMN.
Assuntos
Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/urina , Imunoglobulina G/sangue , Imunoglobulina G/urina , Glomerulonefrite Membranosa/imunologia , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina G/imunologia , Imunossupressores , Rim/patologia , Masculino , Pessoa de Meia-Idade , Proteinúria/tratamento farmacológico , Receptores da Fosfolipase A2/antagonistas & inibidores , Indução de RemissãoRESUMO
OBJECTIVE: To study the distribution characteristics of Beta-fibrinogen (Fg)B gene-854G/A, -455G/A, -249C/T, -148C/T, 448G/A and Bcl-1 G/A polymorphism in North China Han population, and the influence on plasma Fg concentration and molecular reactivity. Further more, to explore the role of Fg gene polymorphisms combining with multi-physiological and environmental factors in the development of cerebral infarction. METHODS: Cluster sampling, health examination and questionnaires surveys of 1652 subjects from Tangshan Kailuan Group Corporation were conducted. Blood biochemistry, Fg concentration, fibrin monomer polymerized velocity (FMPV), absorbance maximum (Amax) and FMPV/Amax were measured. The six polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: In the population, the proportion of the FgB beta-249 T variation allele was 65.49%, while the proportion of the rest loci was predominantly wild type. The significant differences in Fg concentration and FMPV/Amax were found in -854 genotype groups. The Fg concentration in -854GA group was higher than those in GG and AA group. Only the distribution frequencies of FgB beta Bcl-1 A variation allele, GA and AA genotype in the cerebral infarction group were higher than those in non-infarction group, and the prevalence of cerebral infarction in AA genotype group was higher than other groups (the probability value of above-mentioned results were all P<0.01). CONCLUSIONS: FgB beta Bcl-1A allele and variation genotype were susceptible to cerebral infarction. FgB beta-455GA/448G linkage genotype may contribute to the increased plasma Fg concentration. FgB beta-854 was one of the main controlling gene loci for plasma Fg concentration and molecular reactivity.
Assuntos
Povo Asiático/genética , Infarto Cerebral/genética , Fibrinogênio/genética , Polimorfismo Genético , Idoso , Infarto Cerebral/sangue , Feminino , Fibrinogênio/metabolismo , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Since males are at higher risk of cardiovascular diseases than females, the aim of the study was to examine whether there is an association between BP and a polymorphic Hind III biallelic marker in nonrecombining region of Y chromosome in essential hypertension in Tangshan district in China. METHODS: In the study, 225 patients with essential hypertension and 187 healthy people were enrolled into this study as control group. DNA was extracted from white blood cell. Segments of polymorphic Hind III restriction site of the Y chromosome were amplified from DNA by polymerase chain reaction (PCR). PCR products were restricted with 10 U of Hind III for a night at 37 degrees C. The digested products were subjected to electrophoresis in 3% agarose gels, and stained with ethidium bromide. RESULTS: We amplified 178 controls (95.2%) and 216 essential hypertensive patients (96.0%) successfully. Hind III(-) genotype was found in 45.8% of the men in essential hypertension and in 32.0% of the men in the controlled group. The Hind III(-) genotype was significantly higher than that in the controls (chi2 = 7.782, P = 0.007). However, the Hind III(+) genotype was lower in SBP (133.16 mm Hg +/- 21.60 mm Hg vs. 143.58 mm Hg +/- 24.16 mm Hg, P < 0.001), DBP (82.82 mm Hg +/- 11.72 mm Hg vs. 86.82 mm Hg +/- 12.65 mm Hg, P = 0.001), pulse pressure (50.34 mm Hg +/- 14.31 mm Hg vs. 56.76 mm Hg +/- 14.20 mm Hg, P < 0.001) and mean arterial pressure (99.59 mm Hg +/- 14.19 mm Hg vs. 105.74 mm Hg +/- 15.31 mm Hg, P < 0.001) than the Hind III(-) genotype. CONCLUSION: Polymorphic Hind III restriction site of the Y chromosome seemed to be associated with essential hypertension in Tangshan district in China.
Assuntos
Cromossomos Humanos Y/genética , Predisposição Genética para Doença , Hipertensão/genética , Estudos de Casos e Controles , China , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , DNA Metiltransferases Sítio Específica (Adenina-Específica)/metabolismoRESUMO
OBJECTIVE: To explore the relation of angiotensin-converting enzyme (ACE) gene polymorphism, angiotensin II type I receptor (ATIR) gene polymorphism and other factors on cerebral infarction. METHODS: One thousand three hundred fifty-one subjects from Tangshan coalmine were enrolled with study method of cluster sampling. Face to face interviews were conducted to fill in questionnaires by trained interviewers. ACE gene, ATIR gene and inflammation factors including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-8, IL-10, C reactive protein (CRP), fibrinogen (Fg), fibrin monome polymerized velocity (FMPV), absorbance maximum (A(max)), FMPV/A(max), were measured. RESULTS: No different prevalence rates of ACE genotype were found on cerebral infarction. The distributions of AA genotype of ATIR gene in the cerebral infarction was higher than that of the controls. The prevalence of AA genotype was higher than other groups, but the prevalence of combined genotype did not show much difference. Under the existence of factors that related to cerebral infarction, AA genotype frequencies were higher than those of non-smoking and with hypertension. IL-6, ATIR gene polymorphism, sex, FMPV/A(max) were strongly related to cerebral infarction. The level of IL-6 was higher than the normal ones. CONCLUSIONS: The prevalence of cerebral infarction obviously increased in the hypertensive groups having AA genotype of ATIR gene. In the cerebral infarction groups, the level of IL-6 was higher than that in the normal population, indicating that these can be resulted from local inflammation and immunity reactivity. Environmental and genetic factors in the pathogenesis of cerebral infarction might have coordinating functions.
Assuntos
Infarto Cerebral/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Receptor Tipo 1 de Angiotensina/genética , Idoso , Estudos Transversais , Feminino , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: To extract and purify Syk protein from Sf21 cells transfected by Syk gene. METHODS: Sf21 cells were transfected with recombinant syk gene. After 48 h of incubation at 28 degrees Celsius, the transfected cells were collected and sonicated with Sonfier sonicator on ice. Filtered cell extract was loaded onto a Reactive Yellow-3 resin column and Toyopearl AF-Heparin-650 M column respectively. The characters of Syk protein in the fractions were identified by SDS-PAGE, Western blotting and IEF. RESULTS: 225 mg of protein containing Syk were obtained from Sf21 cells (2.5 x 10(9))extract. There were two subpopulations in the elution of Reactive Yellow-3 resin column with the same relative molecular mass (Mr) 72 x 10(3). The two subpopulations were then applied on Toyopearl AF-Heparin-650 M column and two pure proteins were obtained. The results of SDS-PAGE, Western blotting, and IEF showed the two proteins having the same relative molecular mass (72 x 10(3)), corresponding to Syk, but with different pI. CONCLUSION: The yield of Syk was 8 mg from 2.5 billion cells and the purity was > 95%. The two purified Syk proteins have the same Mr and different pI. The purified Syk protein can be applied to study Syk's mechanism, produce anti-Syk antibody and invent Syk diagnosis kit, etc.