RESUMEN
Recent studies suggest that inflammation may play an important role in the pathogenesis of Parkinson's disease (PD). Because the C(-260) --> T polymorphism in the promoter of the CD14 monocyte receptor gene (pCD14) could affect the predisposition to the inflammatory response, we conducted a case-control study to investigate a possible genetic susceptibility of the pCD14 polymorphism in patients with PD. This study included 200 sporadic PD patients and 200 controls, matched by sex and case-control pairs for age at onset in the case. All observed genotype frequencies were in Hardy-Weinberg equilibrium. Results revealed that the CD14-T allele of the pCD14 polymorphism in the female PD patients existed statistically significant difference from that of the female controls (OR = 1.262, P = 0.038), but not for male. Female individuals with homozygote CD14-TT genotype were significantly increased risk of PD by 1.28 time (P = 0.027). Furthermore, a logistic regression analysis confirmed that the homozygote CD14-TT genotype was an independent risk factor for PD (OR = 1.576, P = 0.030). In conclusion, results of this study indicate the pCD14 polymorphism to be a genetic risk factor for PD in females.
Asunto(s)
Receptores de Lipopolisacáridos/genética , Monocitos/metabolismo , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/genética , Anciano , ADN/genética , Etnicidad , Femenino , Frecuencia de los Genes , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Riesgo , Caracteres SexualesRESUMEN
There has been increasing evidence suggesting that inflammatory response maybe involved in the pathogenesis of Parkinson's disease (PD). Alpha1-antichymotrypsin gene (ACT) has been regarded as a susceptibility factor for PD in the past, but the evidence remains controversial. This case-control study was designed to investigate the association of alpha1-antichymotrypsin gene (ACT) polymorphism between 210 Taiwanese patients with clinical definite sporadic PD and 260 controls, matched by age and sex. There were no differences of allelic frequency (A and T) and genotype polymorphism (AA, AT and TT) of the ACT in PD patients from the controls. However, there were significantly fewer early-onset PD (onset age younger than 60 years) or PD women carrying the homozygote AA genotype (ACT-AA) than in controls (p=0.046 and 0.044, respectively). Further analysis revealed that the reduced risk of ACT-AA was particularly significant among PD women with the onset age younger than 60 years (OR=0.796, 95% CI=0.749-0.847, p<0.0001). This study shows that ACT-AA may confer a modest protection against developing early-onset PD in women.
Asunto(s)
Enfermedad de Parkinson/genética , alfa 1-Antiquimotripsina/genética , Edad de Inicio , Anciano , Alelos , Estudios de Casos y Controles , ADN/genética , Etnicidad , Femenino , Frecuencia de los Genes , Genotipo , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Polimorfismo Genético/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Taiwán/epidemiologíaRESUMEN
BACKGROUND AND PURPOSE: Angiotensin I-converting enzyme (ACE) gene deletion polymorphism (D) has recently been suggested as a significant risk factor for cerebrovascular disease in studies involving Japanese and white populations. We investigated the role of ACE D polymorphism in the pathogenesis of cerebrovascular disease in Taiwanese. METHODS: To examine the association of ACE genotype and allele frequency with cerebrovascular disease, we conducted a study of 306 stroke patients and 300 control subjects matched by age and sex. RESULTS: Although the frequencies of both the homozygous deletion (DD) genotype and the D allele were greater in stroke patients than in control subjects, these differences were not significant. Further comparison of the frequencies of the DD genotype and the D allele in the three stroke subgroups (intracerebral hemorrhage, probable large-vessel disease, and probable small-vessel lacunar infarction) with the control group revealed no significant associations. Moreover, ACE gene polymorphism was not significantly associated with age of onset of stroke. Stepwise logistic regression analysis of the presence of the D allele and data on risk factors confirmed the lack of significant association between ACE deletion polymorphism and cerebrovascular disease. Moreover, no association was identified between ACE genotypes and any of the relative risk factors for cerebral infarction or severity of carotid atherosclerosis. CONCLUSIONS: Our results suggest that deletion polymorphism of the ACE gene is not associated with the pathogenesis of cerebrovascular disease in Taiwanese.
Asunto(s)
Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Accidente Cerebrovascular/genética , Alelos , Femenino , Eliminación de Gen , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , TaiwánRESUMEN
BACKGROUND: The association between deletion/insertion polymorphism of the angiotensin I-converting enzyme (ACE) gene and ischemic vascular diseases (IVDs) is still unclear. This study was designed to evaluate the role of ACE gene polymorphism in the pathogenesis of IVDs in a Chinese population living in Taiwan. METHODS: A case-control study was carried out to examine the association of the ACE gene genotype and the allele frequency in 400 IVD patients, including 214 patients with ischemic cerebrovascular disease (ICVD) and 186 patients with ischemic heart disease (IHD), compared with 200 control individuals. RESULTS: Although the patients with ICVD and IHD were found to have higher frequencies of the D/D genotype (22% and 43%) and the D allele (20% and 42%) than the controls (16% and 39%), the statistical differences were not significant, as shown by chi 2 analysis (p > 0.05). Upon further comparison of the frequencies of the D allele among the two sexes and different age subgroups, there was still no significant association. CONCLUSIONS: Deletion polymorphism of the ACE gene was not associated with IVD in a Chinese population in Taiwan. The unique or synergistic effect of other genes that might contribute to the pathogenesis of IVDs needs further investigation.
Asunto(s)
Isquemia Encefálica/genética , Isquemia Miocárdica/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Anciano , Isquemia Encefálica/enzimología , Estudios de Casos y Controles , Femenino , Eliminación de Gen , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/enzimologíaRESUMEN
A G209A mutation in the alpha-synuclein gene was recently discovered in a large Italian kindred and three unrelated Greek kindreds with autosomal dominant Parkinson's disease (PD). Subsequently, another mutation in the gene (G88C) was also identified in a German family with autosomal PD. These results indicate that the alpha-synuclein gene may have an important role in the pathogenesis of PD. This study was designed to screen the existence of both mutations of the alpha-synuclein gene among 100 Chinese patients with PD, including 80 with sporadic and 20 with familial PD. Results showed that none of our patients, both sporadic and familial PD, had either of the two mutations of this gene. We therefore conclude that although of great interest, these two mutations are not relevant for the pathogenesis of PD in a Han Chinese population.
Asunto(s)
Pueblo Asiatico/genética , Proteínas del Tejido Nervioso/genética , Enfermedad de Parkinson/genética , Fosfoproteínas/genética , Mutación Puntual , Anciano , China , Análisis Mutacional de ADN , Femenino , Pruebas Genéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/etnología , Muestreo , Sinucleínas , alfa-SinucleínaRESUMEN
The potential human metastasis molecule CD44 and its isoforms V5 and V6 are overexpressed in human gastric carcinoma. Among the numerous extracellular matrix components, hyaluronate, a CD44 ligand, is of increasing interest in relation to its role in cancer cell development and invasion. By using the dynabead separation method, the SC-M1 cell line was separated into V5 and V6 isoform-positive and -negative populations. The V5 and V6 isoform-negative populations exhibited significantly higher hyaluronate binding activity than the corresponding positive cells. The hyaluronate binding activity of V5 and V6-positive cells could be restored by pretreatment with anti-CD44 V5 and V6 monoclonal antibodies (MAbs). In addition, transfection of aVV5 and V6-negative cells decreased their hyaluronate binding activity to the levels of CD44 V5 and V6-positive cells. Cells transfected with V5 and V6 recovered their hyaluronate binding activity after pretreatment with MAbs against V5 and V6. These data suggest that cell adhesion involving hyaluronate can be regulated by multiple mechanisms, one of which involves alternative splicing of CD44 isoforms.
Asunto(s)
Adenocarcinoma/metabolismo , Receptores de Hialuranos/metabolismo , Ácido Hialurónico/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/inmunología , Empalme Alternativo , Anticuerpos Monoclonales , Western Blotting , Adhesión Celular/fisiología , Humanos , Receptores de Hialuranos/inmunología , Neoplasias Gástricas/inmunología , Transfección , Células Tumorales CultivadasRESUMEN
Deletion polymorphism of angiotensin I-converting enzyme (ACE) gene has been reported to be an independent risk factor for myocardial infarction. Plasminogen activator inhibitor-1 (PAI-1) was proposed to be a link between the renin-angiotensin system and thrombotic risk. This study was undertaken to investigate the possible association between the insertion/deletion (I/D) polymorphism of the ACE gene and plasma PAI-1 levels in 160 patients with mild-to-moderate hypertension. The I/D genotypes were determined by polymerase chain reaction with oligonucleotide primers flanking the polymorphic region in intron 16 of the ACE gene. Baseline levels of PAI-1 antigen and activity and tissue plasminogen activator (t-PA) antigen were determined in fasting morning plasma samples. It was found that patients with homozygote deletion (DD, n = 37) ACE genotype did not have significantly higher plasma levels of PAI-1 antigen (31.2 +/- 15.6 ng/mL v 28.4 +/- 15.1 ng/mL or 27.2 +/- 13.2 ng/mL, P = .42), PAI-1 activity (16.2 +/- 10.6 IU/mL v 14.1 +/- 9.4 IU/ mL or 15.0 +/- 9.9 IU/mL, P = .60), or t-PA antigen (14.6 +/- 6.0 ng/mL v 13.4 +/- 4.9 ng/mL or 14.6 +/- 5.7 ng/mL, P = .40) as compared to those with heterozygote (DI, n = 67) or homozygote insertion (II, n = 56) genotypes. On multiple regression analysis, the ACE genotypes did not appear to be significant predictors for plasma PAI-1 levels and t-PA antigen after adjustment with age, sex, body mass index, plasma triglyceride, cholesterol, and glucose. In conclusion, the results indicated that the I/D polymorphism of the ACE gene was not related to plasma PAI-1 levels in a Chinese population with hypertension. The ACE genotypes may not have a role in influencing the fibrinolysis in hypertension.
Asunto(s)
Hipertensión/genética , Peptidil-Dipeptidasa A/genética , Inhibidor 1 de Activador Plasminogénico/sangre , Polimorfismo Genético , Adulto , Anciano , Glucemia/análisis , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Activador de Tejido Plasminógeno/sangreRESUMEN
AIMS: To determine, by strain identification of Mycobacterium tuberculosis, whether transmission has occurred between individuals or whether new strains are present. METHODS: A rapid protocol for random amplified polymorphic DNA (RAPD) analysis was developed. This protocol was applied to 64 strains of M tuberculosis that had been confirmed by culture and microbiological methods. RESULTS: There are five groups of M tuberculosis prevalent in Taipei city, Taiwan. The major types are groups I and III. Groups I and II had been prevalent until the end of last year when, according to our group analysis, they had been eradicated. However, group III was continuously present from the middle of 1995 to the middle of 1996, and group IV was present at the end of both years, which indicated that both groups were transmitted continuously. These clustered strains had demographic characteristics consistent with a finding of transmission tuberculosis. Also, there were 13 of 64 strains with unique RAPD fingerprints that were inferred to be due primarily to the reactivation of infection. In the drug resistance analysis, the major type represented included group III and part of group IV. CONCLUSIONS: Our preliminary data imply, not only that the prevalence of M tuberculosis in Taipei city is due to transmission rather than reactivation, but that drug resistance also may play a role in tuberculosis transmission.
Asunto(s)
Técnicas de Tipificación Bacteriana , Mycobacterium tuberculosis/clasificación , Técnica del ADN Polimorfo Amplificado Aleatorio , Tuberculosis/transmisión , Dermatoglifia del ADN , Humanos , Mycobacterium tuberculosis/aislamiento & purificación , Prevalencia , Factores de Riesgo , Taiwán/epidemiología , Tuberculosis/epidemiologíaRESUMEN
Reports from different ethnic populations failed to show consistent findings on the association of hypertension with insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene. In this population association study in Chinese, we compared the distribution of the ACE genotypes and allele frequency in 150 healthy controls with normal blood pressure and 148 hypertensive patients categorized by age. Although the frequencies of homozygote deletion (DD) genotype and deletion allele were greater in Chinese with hypertension than in normotensive controls (0.23 vs 0.13 and 0.44 v 0.37, respectively), the differences were not significant by chi2 analysis (P = .07 and .09, respectively). Furthermore, we did not find the trend of decreasing number of DD genotype in older hypertensive Chinese patients. The results indicated a much lower prevalence of ACE/DD genotype in Chinese than in Caucasians and a modest association between I/D polymorphism of the ACE gene and hypertension in Chinese.
Asunto(s)
Pueblo Asiatico/genética , Hipertensión/etnología , Hipertensión/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , China , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIMS: We examined the relationship between apoptosis and three different major stages of human breast carcinoma: intraductal carcinoma (DCIS), infiltrating duct carcinoma (IDC) and metastatic carcinoma in lymph nodes. We also determined the correlation between apoptosis and oestrogen receptor (ER), progesterone receptor (PR) and p53. METHODS AND RESULTS: The study investigates the extent of apoptosis in 63 breast carcinomas by in-situ end-labelling, in formalin-fixed, paraffin-processed tissue sections. The 63 breast carcinomas, included 22 DCISs, 26 IDCs, three infiltrating lobular carcinomas (ILC) and 12 metastatic lymph nodes. The apoptotic labelling index was higher in DCIS than IDC and metastatic carcinoma (P < 0.001, P < 0.007, respectively). By immunohistochemistry, we also analysed p53, ER and PR. Apoptosis correlated significantly with p53 (r = 0.748, P = 0.0004) in IDC. Also, ER correlated significantly with PR (r = 0.629, P = 0.00001). No apparent correlation was found between the apoptosis and ER or PR. CONCLUSION: Our data suggest that not only does apoptosis differ between intraductal carcinoma and infiltrating carcinoma but also it might be regulated by altered p53 expression.
Asunto(s)
Apoptosis , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Proteína p53 Supresora de Tumor/biosíntesis , Neoplasias de la Mama/química , Carcinoma Ductal de Mama/química , Carcinoma Intraductal no Infiltrante/química , Carcinoma Lobular/química , Carcinoma Lobular/patología , ADN Nucleotidilexotransferasa , Nucleótidos de Desoxiuracil , Fluoresceína-5-Isotiocianato , Técnicas Genéticas , Humanos , Inmunohistoquímica , Metástasis Linfática , Persona de Mediana EdadRESUMEN
OBJECTIVES: To investigate ferritin expression in renal carcinoma and the correlation of expression with tumour differentiation and stage. PATIENTS AND METHODS: Ferritin was immunohistologically detected in 35 patients (23 men and 12 women; mean age 58.2 years, range 40-82) with renal carcinoma and the findings compared with cellular type, tumour stage and the ferritin expression of a similar control population of 16 patients. RESULTS: The incidence of ferritin expression in renal carcinomas was 51%. Expression was significantly related to tumour stage and not cellular type. CONCLUSION: The results of this study re-emphasize the high expression of ferritin in renal cell carcinoma and the correlation of expression with tumour behaviour.