Polymorphisms of the low-density lipoprotein receptor gene in Brazilian individuals with heterozygous familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a metabolic disorder inherited as an autosomal dominant trait characterized by an increased plasma low-density lipoprotein (LDL) level. The disease is caused by several different mutations in the LDL receptor gene. Although early identification of individuals carrying the defective gene could be useful in reducing the risk of atherosclerosis and myocardial infarction, the techniques available for determining the number of the functional LDL receptor molecules are difficult to carry out and expensive. Polymorphisms associated with this gene may be used for unequivocal diagnosis of FH in several populations. The aim of our study was to evaluate the genotype distribution and relative allele frequencies of three polymorphisms of the LDL receptor gene, HincII1773 (exon 12), AvaII (exon 13) and PvuII (intron 15), in 50 unrelated Brazilian individuals with a diagnosis of heterozygous FH and in 130 normolipidemic controls. Genomic DNA was extracted from blood leukocytes by a modified salting-out method. The polymorphisms were detected by PCR-RFLP. The FH subjects showed a higher frequency of A+A+ (AvaII), H+H+ (HincII1773) and P1P1 (PvuII) homozygous genotypes when compared to the control group (P<0.05). In addition, FH probands presented a high frequency of A+ (0.58), H+ (0.61) and P1 (0.78) alleles when compared to normolipidemic individuals (0.45, 0.45 and 0.64, respectively). The strong association observed between these alleles and FH suggests that AvaII, HincII1773 and PvuII polymorphisms could be useful to monitor the inheritance of FH in Brazilian families

DNA polymorphisms of apolipoprotein B and AI-CIII-AIV genes in a Brazilian population: a preliminary report

Possible associations between coronary heart disease (CHD) and restriction fragment length polymorphisms (RFLPs) in the apo AI-CIII-AIV cluster and the apo B gene were investigated in a Brazilian population consisting of 46 patients with CHD and 24 individuals without evidence of CHD. A preliminary genetic analysis of SstI RFLP in the apo AI-CIII-AIV cluster showed a significantly higher frequency of the rare SstI allele (S2) in CHD patients as compared with controls. No significant differences were found in the frequencies of PstI RFLP in the apo AI-CIII-AIV cluster or XbaI and EcoRI RFLPs in the apo B gene between CHD patients and controls. Moreover, no association was seen between the RFLPs studied and myocardial infarction or plasma cholesterol or triglyceride levels.

Fatores de risco para doença arterial coronariana em crianças e adolescentes filhos de coronariopatia jovens / Coronary risk factors in children of young coronary artery disease patients

Objetivo - verificar a prevalência dos fatores de risco (FR) em crianças e adolescentes filhos de coronariopatas. Métodos - em 280 filhos de coronariopatas jovens (< 55 anos), submetidos à cirurgia de revascularizaçäo miocárdica, foi determinada a frequência de desvios dos valores considerados ideiais para a faixa etária da colesterolemia total-CT, trigliceridemia-TG, HDL-C e LDL-C, glicemia, da pressäo arterial (PA), do peso corpóreo (através do índice de Newen-Goldstein-ING). Foram também verificas as frequências do hábito de fumar, e de alteraçöes eletrocardiográficas. Crianças de 2 a 12 anos formaram o grupo GA e adolescentes de 12 a 19 anos formaram o grupo GB. Eventuais associaçöes entre o FR e a influência dos fatores idade, sexo, peso corpóreo e tabagismo sobre as variáveis lipídicas também foram estudadas. Resultados - no conjunto estudado, 48,2 por cento e 44,6 por cento apresentaram respectivamente valores de CT e LDL-Cacima dos considerados ideais, sendo que 21,7 por cento e 26,1 por eto apresentavam valores indicativos de risco também para adultos. TG acima de 200 mg/dl ocorreur em 1,4 por cento da amostra e valores diminuídos de HDL-C em 16,8 por cento. O sobrepeso e obesidade estiveram presentes, respectivamente, em 13,1 por cento e 20,0 por cento (12,9 por cento e 31,4 por cento em GA e 13,2 por cento e 15,8 por cento em GB) e influenciaram os níveis de TG. Tabagismo ocorreu em 10,4 por cento; houve somente 3 casos de hipertensäo arterial. Näo foram encontradas anormalidades da liemia e nem alteraçöes eletrocardiográficas. Conclusäo - a investigaçäo reitera a necessidade de particular atençäo preventiva nos filhos de coronariopatas jovens, considerando a levada frequência de desvios do metabolismo lipídoco e de aumento do peso corpóreo (sobrepeso e obesidade)

Purpose - To determine whether children and adolescents, whose fathers have established coronary artery disease (CAD), have increased prevalence of coronary rishfactors (RF). Methods - The frequencies of abnormal values of lipid variables, glucose, blood pressure, obesity index (calculated through Newen-Goldstein index), smoking and electrocardiographic alterations (ECG), were assessed in 280 descendents of young revascularized patients (<55 years). The study population was divided in two groups according to age, respectivelly GA (2 to 12 years) and GB (12 to 19 years). Eventual influences ofage, gender, obesity and smoking on lipid variable were evaluated through variance analysis. Results - Of the study population, 48.2% and 44.6% had total cholesterol (TC) and LDL-C respectively above the desirable values; 21.7% and 26.1% had values similar to adults under increased risk. Triglyceridemia (TG) >200mg/dl was found in 1.4% of the sample and lower values of HDL-C in 16.8%. Overweight and obesity were observed in 13.1% and 20.0% of the patients and influenced TG levels in GB. Smoking occurred in 10.4%; hypertension in 3 cases and none had abnormal glucose levels or ECG. Conclusion - Healthy children of fathers with established CAD, exhibit a high freqüency of altered lipid profile and increased body weight. The results suggest the need for early identification of RF in offspring of young CAD patients, thus emphasizing changes in risk profile and improving lifestyle