Molecular basis of familial hypercholesterolemia in Brazil: Identification of seven novel LDLR gene mutations.

Low-density lipoprotein receptor (LDLR) gene mutations cause familial hypercholesterol-emia (FH), one of the most common single gene disorders. The spectrum of LDLR mutations in Brazil is not known. The aim of this study was the characterization of LDLR mutations in 35 unrelated Brazilian patients with heterozygous FH. The promoter region, the 18 exons and the flanking intron sequences of the LDLR gene were screened by PCR-SSCP analysis and by DNA sequencing. In addition, we have screened the apolipoprotein B gene (APOB) for known mutations (R3500Q and R3531C) that cause Familial defective apo B-100 (FDB) by PCR-RFLP procedure. We found two nonsense (E92X and C371X) and six missense LDLR mutations (R236W, G322S, G352D, A370T, C675W and C677Y), that were previously described in FH patients from other populations. We also found five novel missense [G(-20)R, T476P, V503G, D580H and S652R] and two novel frame shift LDLR mutations (FsR757 and FsS828). Four patients were found to carry two different mutations in the LDLR gene: G352D and A370T (one patient), S652R and C675W (one patient) and T476P and V503G (two patients). APOB mutations were not found. These findings demonstrate that there is a broad spectrum of mutations in the LDLR gene in FH individuals from Brazil.

A method to detect the G894T polymorphism of the NOS3 gene. Clinical validation in familial hypercholesterolemia.

An endothelial nitric oxide synthase gene (NOS3) polymorphism in exon 7 (G894T), resulting in Glu298Asp substitution at protein level, has been associated with myocardial infarction, hypertension and coronary atherosclerosis in some populations. This polymorphism is usually identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). However, the procedures described to date do not eliminate the possibility of misclassification and either require confirmation by DNA sequencing or are time-consuming. In this study, a PCR-RFLP procedure to detect the G894T polymorphism at the NOS3 was optimized by the introduction of a constitutive cleavage site in the amplification product. This cleavage site provides an internal control for enzymatic activity to avoid mistyping. The method was validated by the study of 35 white unrelated individuals with familial hypercholesterolemia and 70 controls. The frequency of the variant allele (T) was similar between both groups (27% vs. 22%, NS), and comparable to the frequency found in other white populations. However, future studies are necessary to confirm these data. In summary, the optimized procedure for detection of the G894T NOS3 polymorphism is rapid, simple, and does not require confirmatory tests. Using this method, we found no association between this polymorphism and familial hypercholesterolemia.

Perfil lipídico de indivíduo submetidos à cinecoronariografia em diferentes regiöes do Brasil / Lipid profie of individuals subjected to coronary angiography in four brazilian regions

OBJETIVO: Analisar o perfil lipídico e, paralelamente, a prevalência de fatores de risco (FR) näo lipídicos, em indivíduos com menos de 65 anos submetidos à cinecoronariografia em quatro regiöes do Brasil. MÉTODOS: Em 260 homens e 144 mulheres, consecutivamente encaminhados pela primeira vez à cinecoronariografia, foram determinados os valores sangüíneos de glicose, colesterol total (CT), triglicérides (TG), fraçöes HDL-colesterol (HDL-C) E LDL-colesterol (LDL-C) e analisadas as prevalência de hipertensäo arterial, tabagismo, diabetes, obesidade, sedentarismo, história familiar. RESULTADOS: Pacientes com DAC apresentaram significantemente valores médios elevados de CT, TG e LDL-C e menores de HDL-C e maior freqüência de valores indesejáveis dessas fraçöes. Entre eles, as mulheres com idade >= 50 anos tiveram maiores valores médios de CT, HDL-C e LDL-C e maior freüência de CT >= 200 e de LDL-C >= 130 mg/dL; os homens mostraram valores médios maiores de TG e menores de HDL-C. Os maiores valores médios de CT foram observados nos coronariopatas do do centro-oeste. Diabetes e tabagismo foram mais freüêntes nos portadores de DAC; a prevalência de diabetes foi maior nas mulheres com idade >= 50 anos e a de tabagismo nas mais jovens. As prevalência de hipertensäo, sedentarismo, obesidade e história familiar foram semelhantes nos grupos com e sem DAC. Coronariopatas do sul apresentaram freqüência maior de tabagismo e história familiar e menor de sedentarismo. CONCLUSÄO: Alteraçöes do perfil lipídico e diferenças na prevalência de FR foram encontradas em mulheres e homens com DAC. Entretanto, essas diferenças näo foram uniformes nas quatro regiöes do país e podem ser explicadas pelas grandes disparidades sócio-econômicas e culturais existentes entre elas.

Purpose - To analyse the lipid profile and also nonlipid risk factors (RF) in individuals <65 years subjected to coronary angiography in four Brazilian regions. Methods - We determined in mg/dL plasma glucose, total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) in 260 men and 144 women consecutively subjected to a first coronary angiography in 11 cardiologic centers of 4 Brazilian regions. We also analysed frequencies of hypertension, smoking, diabetes, obesity, sedentary habits and family history. Results - CAD patients exhibited higher mean values of TC, TG and LDL-C and lower of HDL-C and higher frequencies of undesirable values of those variables. CAD women >50 yrs showed higher mean values of TC, HDL-C and LDL-C and higher frequencies of TC >200 and LDLC >130 mg/dL. CAD men showed higher mean values of TG and lower of HDL-C. Higher mean values of TC were observed in CAD patients from Middle-West.Diabetes and smoking were more frequent in CAD; higher prevalence of diabetes was found in women >50 yrs and of smoking in those <50 yrs. No differences between CAD and control were observed regarding hypertension, sedentary habits, obesity and family history. CAD from South exhibited higher frequencies of smoking and family history and lower of sedentary habits. Conclusion - CAD exhibited differences on the lipid profile and on the prevalence of non lipid risk factor than controls. These differences were not similar in four Brazilian regions. This may reflect different lifestyles from region to region and probably depends on the different socio-economic and educational levels

Intervençäo sobre tabagismo realizada por cardiologista em rotina ambulatorial / Anti-smoking intervention performed by cardiologist during ambulatory care

OBJETIVO: Avaliar a efetividade da intervençäo sobre o tabagismo, realizada por médico cardiologista em rotina de ambulatório, utilizando a prescriçäo de adesivos de nicotina. MÉTODOS: Foram avaliados, consecutivamente, 100 pacientes (50 homens e 50 mulheres), incluindo consulta médica, aplicaçäo de escore para definiçäo do grau de dependência à nicotina, determinaçäo da concentraçäo de monóxido de carbono expirado e peso corpóreo. Os adesivos foram utilizados entre 8 e 12 semanas, com reduçäo progressiva da concentraçäo até a suspensäo (concentraçöes de 21, 14 e 7 mg). RESULTADOS: A taxa de abstinência um ano após o início do tratamento foi de 41 "por cento", confirmada pela concentraçäo do monóxido de carbono. CONCLUSÄO: A intervençäo sobre o tabagismo pode ser realizada em rotina de atendimento cardiológico com resultados satisfatórios. Os adesivos de nicotina säo seguros, bem tolerados, e devem ser utilizados, mais freqüêntemente, no auxílio aos fumantes, para deixarem de fumar.

Fatores de risco para doenças cardiovasculares em médicos: dados preliminares do projeto VIDAM da Associaçäo Paulista de Medicina / Risk Factors for Cardiovascular Diseases in Physicians. Preliminary Data from VIDAM Project of "Associação Paulista de Medicina"

PURPOSE--To evaluate the frequency and other characteristics of some cardiovascular risk factors among physicians of Säo Paulo State, Brazil. METHODS--From a questionnaire, 1395 voluntary physicians answered questions about personal and familial cardiovascular disease and risk factors, and blood pressure, serum total cholesterol, glucose, height and weight were recorded. RESULTS--The frequency of familial history of ischemic heart disease was 24.4 per cent; positive personal antecedent of hypercholesterolemia, 12.4 per cent; serum total cholesterol > or = 240 mg/dl, 14.3 per cent; positive personal antecedent of hypertension, 8.4 per cent; systolic blood pressure > or = 140 mmHg or diastolic > or = 90 mmHg, 23.8 per cent; current cigarette smokers, 17.4 per cent; prior cigarette smokers, 19.1 per cent; positive personal antecedent of diabetes, 0.8 per cent; serum glucose > 120 mg per cent, 7.7 per cent; sedentarism, 37 per cent, and obesity, 17.2 per cent. CONCLUSION--Cigarette smoking was the only risk factor that was taken in account with emphasis by the physicians of Säo Paulo State in order to prevent themselves from cardiovascular disease