Effects of APOE, APOB and LDLR variants on serum lipids and lack of association with xanthelasma in individuals from Southeastern Brazil

Xanthelasma might be a clinical manifestation of dyslipidemia, a recognized risk factor for coronary artery disease. We investigated the association of apolipoprotein E (APOE HhaI), apolipoprotein B (APOB XbaI and Ins/Del) and LDL receptor (LDLR AvaII and HincII) gene polymorphisms with lipid profiles in 100 Brazilians with xanthelasma and 100 controls. Allele frequencies were similar in both groups. APOE, APOB and LDLR genotypes were not correlated with differences in the serum lipid profile. In individuals with xanthelasma, the APOB D allele was associated with less chance of having increased LDL-cholesterol (O.R. = 0.16, CI95 percent = 0.03-0.94, p = 0.042). In the control group, the APOB X+ allele was associated with less chance of having both increased total cholesterol (O.R. = 0.16, CI95 percent = 0.03-0.78, p = 0.023) and increased LDL-cholesterol (O.R. = 0.10, CI95 percent = 0.02-0.60, p = 0.012). Moreover, there was a significantly higher frequency of control individuals (68 percent) with elevated serum triglyceride levels, compared to patients (48 percent, p = 0.008). On the other hand, triglyceride levels in controls also seemed to be influenced by all other gene polymorphisms studied, an effect that might be enhanced by environmental factors.

Influência dos hormônios esteróiodes sexuais no tempo de esqueletização de ratos wistar / Influence of steroid sexual hormones on skeletization time of wistar rats

A estimativa do tempo de morte é um dos problemas mais complicados e difíceis da Medicina Legal devido aos diversos fatores que interferem nesse processo (temperatura, umidade, condições aeróbica e anaeróbica, presença de microrganismos e condições do solo). Fatores intrínsecos ao corpo freqüentemente não são relacionados à decomposição corporal. Para investigar se o processo de esqueletização sofre interferência dos hormônios esteróides sexuais foi realizado um trabalho experimental com ratos Wistar (30 machos e 60 fêmeas divididos em subgrupos em diferentes fases hormonais). Os animais foram cuidados até atingirem o peso entre 350 e 450g, quando foram mortos em câmara de CO2 e sepultados. A análise dos fatores ambientais (temperatura, umidade do ar e chuvas) e corporais (peso e gordura corporal) mostrou que a variação destes não interferiu no processo de esqueletização. Após as exumações, apenas o grupo de machos controles para testosterona apresentou esqueletização completa. Os machos castrados sem reposição de testosterona e os machos castrados com reposição de testosterona apresentaram esqueletização mínima. Todos os grupos das fêmeas apresentaram esqueletização parcial. A análise dos resíduos de putrefação dos grupos com esqueletização mínima e parcial evidenciou a presença de ácidos graxos característicos da composição de adipocera. Considerando-se que os dois grupos de animais (machos e fêmeas) foram sepultados no mesmo local, sob as mesmas condições ambientais e corporais, durante o mesmo intervalo de tempo, é possível concluir que os hormônios esteróides sexuais são responsáveis pela diferença observada na decomposição corpórea, sendo a testosterona o principal interveniente neste processo. Além disso, o modelo experimental também evidenciou o potencial de utilização para ser utilizado futuramente em estudos do processo de formação de adipocera.

The establishment of the postmortem interval is one of the most complicated and difficult tasks in forensic investigation because of many factors that affect this process (temperature, humidity, aerobic and anaerobic conditions, presence of microorganisms and soil conditions). Body intrinsic factors frequently not are related to de body decomposition. To investigate if the skeletonization process is under interference of sexual steroid hormones an experimental investigation with Wistar rats was done (30 male and 60 females divided in sub-groups at different hormonal phases). The animals were raised until they reach body weight between 350 and 450g, when were killed in a CO2 chamber and buried. Analysis of the environmental (temperature, humidity and rain) and corporal factors (body weight and body fat) showed that variation in these factors did not interfere on the skeletonization process. After the exhumation, only the male control group for testosterone showed complete skeletonization. The castrated males with no testosterone reposition and the castrated males with testosterone reposition showed minimum skeletonization. All female groups showed partial skeletonization. Analysis of the putrefaction residues from the groups with partial and minimum skeletonization showed the presence of the characteristic fatty acids of adipocere composition. Considering that both animal groups (males and females) were buried at the same place, under the same environmental and body conditions, during the same time interval, it is possible to conclude that sexual steroid hormones are responsible for the observed difference in body decomposition, being testosterone the main intervenient factor in this process. Besides, the experimental model also evidenced its potential use for future studies in the process of adipocere formation.

Avaliação da relação entre o polimorfismo C677T no gene para MTHFR e a concentração plasmática de homocisteína na doença arterial coronariana / Evaluation of MTHFR C677T gene polymorphism and homocysteine level in coronary atherosclerotic disease / Evaluation of MTHFR C677T gene polymorphism and homocysteine level in coronary atherosclerotic disease

OBJETIVO: O objetivo deste trabalho é determinar a prevalência do polimorfismo C677T do gene metilenotetraidrofolato redutase (MTHFR) e associá-la com a concentração plasmática de homocisteína plasmática na doença arterial coronariana (DAC). MÉTODOS: Foram avaliados 93 pacientes com DAC documentada, atendidos no Hospital Universitário Oswaldo Cruz (Recife, PE, Brasil), e 108 controles sem a doença. Foram determinados os perfis lipídicos de pacientes e controles. As concentrações plasmáticas de homocisteína e folato foram determinadas por HPLC e quimioluminescência, respectivamente. A genotipagem foi realizada por RFLP/PCR. RESULTADOS: Os grupos de pacientes e controles foram homogêneos quanto aos perfis genéticos do polimorfismo investigado. Nos pacientes, as concentrações plasmáticas médias de homocisteina (11,7 ± 4,4 æmol/L) e de folato (6,22 ± 3,0 ng/dL) foram estatisticamente diferentes daquelas observadas nos controles (8,84 ± 3,2 æmol/L e 7,69 ± 3,1 ng/dL, respectivamente), ao nível de significância de 0,05. Entretanto, não houve correlação entre concentração plasmática de homocisteína e folato nos pacientes (r= -0,202). Não foi observada associação entre a homozigosidade 677TT para MTHFR e a concentração plasmática de homocisteína sérica (p= 0,634). A comparação dos casos e controles que apresentaram simultaneamente alta concentração plasmática de homocisteína e baixa concentração de folato, resultou numa razão de chance superior à de cada variável analisada independentemente (RC= 11,9; IC 95 por cento= 4,16-34,42, p< 0,01). CONCLUSÕES: A mutação C677T não parece ser um fator genético importante capaz de explicar a hiperhomocisteinemia moderada observada nos pacientes com DAC. Outros fatores, ambientais e genéticos, devem ser investigados.

OBJECTIVE: The aim of this study is to determine the prevalence of C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism and correlate it with plasma homocysteine levels in coronary artery disease (CAD). METHODS: Ninety-three patients with documented CAD from Hospital Universitário Oswaldo Cruz (Recife, PE, Brazil) and 108 healthy controls were evaluated. Homocysteine and folate levels were determined by HPLC and chemoluminescence, respectively, and lipid profile was considered. Genotyping was done by RFLP/PCR. RESULTS: The groups were homogeneous for the C677T polymorphisms. The homocysteine level in cases (11.7 æmol/L) was statistically different from that observed in controls (8.84 æmol/L, p< 0.05). It was also observed that 72 percent of the patients had homocysteine values above12 æmol/L while the control group presented only 32 percent in this range. There was no relationship between homozigosity for the C677T polymorphism and the homocysteine level (p= 0.634). We noticed statistical differences between folate levels from patients and controls (6.22 and 7.69 ng/dL, p< 0.05, respectively). However, there was no correlation between homocysteine and folate concentrations in the entire group (r= -0.202). Comparing cases and controls, the odds ratio (OR) when homocysteine is high and folate is low was OR= 11.9; CI 95 percent= 4.16-34.42, p< 0.01. CONCLUSION: A lack of correlation between C677T mutation and homocysteine level suggests that environmental factors and others genetic factors seem to exert more influence on homocysteine level in this population.