Mechanism of Xianglian Pills in improving dyslipidemia in obese mice induced by high-fat diet based on network pharmacology and intestinal flora / 中国中药杂志

The present study aimed to investigate the effect of Xianglian Pills(XLP) on lipid metabolism in obese mice and explore the underlying mechanism based on network pharmacology and intestinal flora. Firstly, network pharmacology was used to predict the possible effect of XLP on obesity. Secondly, an obese mouse model induced by a high-fat diet was established to observe changes in mouse body weight, adiposity index, liver and adipose tissue pathology. Lipid profiles, liver and kidney function markers, insulin content, and the expression of recombinant uncoupling protein 1(UCP-1) and PR structural domain protein 16(PRDM16) were measured. The 16S rRNA gene sequencing technology was used to analyze the changes in the intestinal flora. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that XLP mainly played a role in improving obesity by regulating lipolysis, type 2 diabetes mellitus, and insulin resistance. The results of animal experiments showed that XLP significantly reduced body weight, adiposity, blood lipid levels, and serum insulin levels in obese mice, while enhancing the expression of UCP-1 and PRDM16 in adipose tissue without causing damage to the liver or kidneys. The 16S rRNA gene sequencing results showed that XLP decreased the Firmicutes/Bacteroidetes(F/B) ratio at the phylum level, increased the relative abundance of Akkermansia and Bacteroides at the family and genus levels, and reduced the abundance of Allobaculum. Therefore, XLP can effectively improve lipid metabolism disorders in high-fat diet-induced obese mice, and the mechanism is related to the improvement of brown adipose function, the browning of white fat, the accelerated lipid metabolism, and the improvement of intestinal flora. However, its effect on promoting the conversion of white adipose to brown adipose still needs to be further studied.

Polymorphisms of the Vitamin D Receptor Gene and Sex-Differential Associations with Lipid Profiles in Chinese Han Adults / 生物医学与环境科学（英文）

OBJECTIVE@#To explore the association of single nucleotide polymorphisms (SNPs) of the vitamin D receptor gene ( VDR) with circulating lipids considering gender differences.@*METHODS@#Of the Han Chinese adults recruited from a health examination center for inclusion in the study, the circulating lipids, 25-hydroxyvitamin D (25OHD), and other parameters were measured. The VDR SNPs of Cdx2 (rs11568820), Fok1 (rs2228570), Apa1 (rs7975232), and Taq1 (rs731236) were genotyped with a qPCR test using blood DNA samples, and their associations with lipids were analyzed using logistic regression.@*RESULTS@#In the female participants ( n = 236 with dyslipidemia and 888 without dyslipidemia), multiple genotype models of Fok1 indicated a positive correlation of B (not A) alleles with LDLC level ( P < 0.05). In the male participants ( n = 299 with dyslipidemia and 564 without dyslipidemia), the recessive model of Cdx2 and the additive and recessive models of Fok1 differed ( P < 0.05) between the HDLC-classified subgroups, respectively, and Fok1 BB and Cdx2 TT presented interactions with 25OHD in the negative associations with HDLC ( P < 0.05).@*CONCLUSION@#In the Chinese Han adults included in the study, the Fok1 B-allele of VDR was associated with higher LDLC in females, and the Fok1 B-allele and the Cdx2 T-allele of VDR were associated with lower HDLC in males. The interaction of VD and Fok1 BB or Cdx2 TT in males synergistically decreased HDLC levels.

Danlou Tablet Improves Chronic Intermittent Hypoxia-Induced Dyslipidemia and Arteriosclerosis by HIF-1α-Angptl4 mRNA Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To detect whether Danlou Tablet (DLT) regulates the hypoxia-induced factor (HIF)-1α-angiopoietin-like 4 (Angptl4) mRNA signaling pathway and explore the role of DLT in treating chronic intermittent hypoxia (CIH)-induced dyslipidemia and arteriosclerosis.@*METHODS@#The mature adipocytes were obtained from 3T3-L1 cell culturation and allocated into 8 groups including control groups (Groups 1 and 5, 0.1 mL of cell culture grade water); DLT groups (Groups 2 and 6, 0.1 mL of 1,000 µg/mL DLT submicron powder solution); dimethyloxalylglycine (DMOG) groups (Groups 3 and 7, DMOG and 0.1 mL of cell culture grade water); DMOG plus DLT groups (Groups 4 and 8, DMOG and 0.1 mL of 1,000 µg/mL DLT submicron powder solution). Groups 1-4 used mature adipocytes and groups 5-8 used HIF-1 α-siRNA lentivirus-transfected mature adipocytes. After 24-h treatment, real-time polymerase chain reaction and Western blot were employed to determine the mRNA and protein expression levels of HIF-1 α and Angptl4. In animal experiments, the CIH model in ApoE-/- mice was established. Sixteen mice were complete randomly divided into 4 groups including sham group, CIH model group [intermittent hypoxia and normal saline (2 mL/time) gavage once a day]; Angptl4 Ab group [intermittent hypoxia and Angptl4 antibody (30 mg/kg) intraperitoneally injected every week]; DLT group [intermittent hypoxia and DLT (250 mg/kg) once a day], 4 mice in each group. After 4-week treatment, enzyme linked immunosorbent assay was used to detect the expression levels of serum total cholesterol (TC) and triglyceride (TG). Hematoxylin-eosin and CD68 staining were used to observe the morphological properties of arterial plaques.@*RESULTS@#Angptl4 expression was dependent on HIF-1 α, with a reduction in mRNA expression and no response in protein level to DMOG or DLT treatment in relation to siHIF-1 α -transfected cells. DLT inhibited HIF-1 α and Angptl4 mRNA expression (P<0.05 or P<0.01) and reduced HIF-1 α and Angptl4 protein expressions with DMOG in mature adipocytes (all P<0.01), as the effect on HIF-1 α protein also existed in the presence of siHIF-1 α (P<0.01). ApoE-/- mice treated with CIH had increased TG and TC levels (all P<0.01) and atherosclerotic plaque. Angptl4 antibody and DLT both reduce TG and TC levels (all P<0.01), as well as reducing atherosclerotic plaque areas, narrowing arterial wall thickness and alleviating atherosclerotic lesion symptoms to some extent.@*CONCLUSION@#DLT had positive effects in improving dyslipidemia and arteriosclerosis by inhibiting Angptl4 protein level through HIF-1 α-Angptl4 mRNA signaling pathway.

Association Between Homocysteine Level and Methylenetetrahydrofolate Reductase Gene Polymorphisms in Type 2 Diabetes Accompanied by Dyslipidemia / 中国医学科学杂志(英文版)

Objective To investigate the association between total homocysteine (tHcy) level in plasma and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus (T2DM) accompanied by dyslipidemia. Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively. Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C. Plasma tHcy and lipid levels were measured as well. The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test. Plasma tHcy level of T2DM patients who carried the different genotypes was compared by Student's t test. Results Finally, 82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study. There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism in T2DM patients (t=2.27, P=0.02). Moreover, the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677 TT genotype was significantly higher than that in those with CT+CC genotype (13.62±6.97 vs. 10.95±3.62 μmol/L, t=2.20, P=0.03); while for patients without dyslipidemia, comparison of the tHcy level between those who carried the above two alleles showed no significantly difference (13.34±6.03 vs. 12.04±5.09 μmol/L, t=1.08, P=0.29). Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.

Importância da educação para prevenção cardiovascular / Importance of education for cardiovascular disease prevention

As doenças cardiovasculares estão entre as maiores causas de morbidade e mortalidade em todo o mundo e são responsáveis por um elevado custo para os sistemas de saúde. Assim, as medidas de prevenção dessas doenças e o controle de seus fatores de risco tornam-se essenciais. Para isso, temos como alternativa, intervenções educacionais para a população, como maneira de fortalecer o indivíduo para realizar as mudanças necessárias em seu estilo de vida, e medidas de educação profissional, para difundir o manejo de emergências cardiovas-culares, com grande impacto na sobrevida de indivíduos com esses problemas. Neste texto, procuramos descrever as medidas educacionais mais frequentes e efetivas para essa prevenção.

Cardiovascular disease is one of the leading causes of morbidity and mortality worldwide and represents a high cost for health systems. Therefore, measures to prevent these conditions and to control their risk factors are essential. One alternative consists of educational interventions for the population as a means of enabling the individual to make the necessary changes in their lifestyle, as well as professional education measures to disseminate the management of cardiovascular emergencies with considerable impact on the survival of individuals with these problems. In this text, we strive to describe the most common and effective educational measures for this prevention

Intervenção sobre fatores de risco emcrianças e adolescentes / Risk factor intervention in children and adolescents

As doenças cardiovasculares estão entre as principais causas de mortalidade no mundo e não afligem apenas os adultos. Muitos trabalhos têm demonstrado que elas já podem ser vistas na infância. Entre os fatores de risco para a doença cardiovascular, pode-se destacar a dislipidemia, o baixo peso ao nascer e a obesidade infantil. A detecção de dislipidemia na infância é crucial, por ser considerada a fase estratégica para a implementação de medidas de prevenção da aterosclerose no âmbito populacional. Embora as causas ambientais ou poligênicas sejam as mais frequentes, é importante a identificação de formas genéticas como a hipercolesterolemia familiar e hipertrigliceridemias de base genética, pois medidas relacionadas aos hábitos de vida e terapêutica medicamentosa devem ser iniciadas preco-cemente, evitando-se complicações e mudando a história natural dos desfechos clínicos. Outros estudos têm demonstrado que o baixo peso ao nascer também contribui para o desenvolvimento tardio de hipertensão arterial, doença coronariana e disfunção endotelial. Possivelmente, por conta das agressões ao sistema vascular em desenvolvimento. No en-tanto, os mecanismos ainda são incertos. Evidências sugerem que alguns biomarcadores, tais como os níveis de ácido úrico e homocisteína e a baixa concentração de óxido nítrico observados em crianças com baixo peso ao nascer, podem estar associados a alterações deletérias na vida adulta. Por fim, o terceiro fator que deve ser considerado é a obesidade infantil. Essa desordem tem causa multifatorial e pode favorecer o surgimento das etapas iniciais da aterosclerose, como a disfunção endotelial, já na infância. Porém, é um fator de risco modificável, e as estratégias de prevenção e intervenção baseiam-se, na maioria dos casos, em mudanças do estilo de vida, como alimentação saudável e exercício físico.

Cardiovascular disease is one of the leading causes of mortality in the world and does not affect adults alone. Many papers have shown that it can already be seen in childhood. The most significant risk factors for cardiovascular disease include dyslipidemia, low birth weight and childhood obesity. Screening for dyslipidemia in childhood is crucial as this is considered a strategic phase for the implementation of measures aimed at preventing atherosclerosis in the population setting. Although environment or polygenic causes are the most common, it is important to identify genetic forms such as familial hypercholesterolemia and hypertriglyceridemia, since measures related to lifestyle and pharmacotherapy must be initiated early in life to avoid complications and change the natural history of clinical outcomes. Other studies have shown that low birth weight also contributes to the late development of hypertension, coronary artery disease and endothelial dysfunction, possible due to injury to the developing vascular system. However, the mechanisms are still uncertain, and evidence suggests that some biomarkers, such as uric acid and homocysteine levels, and the low concentration of nitric oxide observed in low birthweight children, may be associated with deleterious changes in adulthood. Finally, the third factor to be considered is childhood obesity. This disorder has a multifactorial etiology and may favor the onset of the first stages of atherosclerosis, such as endothelial dysfunction, in young children. However, it is a modifiable risk factor, and prevention and intervention strategies are largely based on lifestyle changes such as healthy diet and exercise

Polymorphisms in PPARG and APOE: relationships with lipid profile of adolescents with cardiovascular risk factors

BACKGROUND: Cardiovascular diseases constitute the main death cause worldwide resulting from a combination of genetic and lifestyle factors, and the prevalence among younger individuals has increased. It is important to early identify changes in lipid profile and the influence of genetic variations in specific genes on the individual patterns of lipid profile. Thus, the aim of this study was to verify the relationship of polymorphisms in PPAR-gamma gene (PPARG−rs1801282−Pro12Ala) and in apolipoprotein E gene (APOE−rs429358 + rs7412, determinants of the APOE2, APOE3, or APOE4 genotypes) with lipid profile of adolescents under cardiovascular risk factors. METHODS: This was a cross-sectional study with 115 adolescents aged 10­19 years, which presented cardiovascular risk factors. The students were evaluated regarding socioeconomic, anthropometric, biochemical, genetic, and dietetic variables. Student'sttest or Mann-Whitney test were applied to the analysis of the genotypes. Multiple linear regression analysis was performed to determine the variables that most influenced the lipid profile. RESULTS: Adolescents carrying PPARG Ala allele showed higher serum triglycerides (p= 0.0423) and very low-density lipoprotein (p= 0.0410) levels when compared to those carrying the wild genotype. For the APOE polymorphism, it was observed a trend of higher triglycerides (p= 0.0712) and very low-density lipoprotein (p= 0.0758) levels in the adolescents carrying the E4 allele when compared to those who did not carry this allele. CONCLUSION: The polymorphisms PPARGrs1801282 andAPOErs429358 + rs7412 seem to be related to the development of lipid profile alterations in adolescents.

Family history of cardiovascular disease and non-HDL cholesterol in prepubescent non-obese children / Importância clínica da história familiar de doença cardiovascular e da dosagem do colesterol não HDL em crianças eutróficas

Summary Objective: To describe the values of non-HDL cholesterol (NHDL-c) and the frequency of a family history of early cardiovascular disease (family HCVD) in healthy prepubescent children. Analyze the association between NHDL-c and family HCVD, and possible associations with other risk factors for cardiovascular disease (CVD). Method: Cross-sectional study including 269 prepubescent (aged 6-10 years) schoolchildren with a normal body mass index (+1SD<BMI>-2SD). Data collected: Family HCVD; weight and height, waist circumference and systemic blood pressure; lipid profile (total cholesterol TC, HDL-c, triglycerides and LDL-c), NHDL-c calculation (CT-HDL-c, cut-off = 145 mg/dL) and insulin resistance (HOMA-IR). Results: High levels were found for NHDL-c in 10 (3.7%) of these schoolchildren, and family early HCVD was found in 46 (17.1%) of them. There was a weak association between family HCVD and NHDL-c (Cramer’s-V-test = 0.120; p=0.050). Among the children with NHDL-c≥145 mg/dL, 4 (40%) have family HCVD. The presence of family HCVD was not associated with the variables being studied. The variables independently associated with NHDL-c ≥ 145 mg/dL were: HOMA-IR (OR=1.7; 95CI 1.1-2.6) and diastolic blood pressure (OR=1.1; 95CI 1.02-1.2). Conclusion: NHDL-c values were associated with blood pressure and insulin resistance. Family HCVD was not associated with other classic risk factors for CVD, even though the frequency found was five times higher than that of high NHDL-c.

Resumo Objetivos: descrever os valores do colesterol não HDL (NHDL-c) e a frequência de história cardiovascular familiar precoce (HDCV familiar) em crianças eutróficas e pré-púberes. Analisar a associação entre o NHDL-c e o HDCV familiar e possíveis associações com outros fatores de risco para doenças cardiovasculares (DCV). Método: estudo transversal com 269 escolares (6-10 anos) pré-púberes e com índice de massa corporal normal (+1DP<IMC>-2DP). Dados coletados: HDCV familiar; peso e estatura, circunferência abdominal e pressão arterial sistêmica; perfil lipídico (colesterol total – CT, HDL-c, triglicérides e LDL-c), cálculo do NHDL-c (CT-HDL-c, ponto de corte 145 mg/dL) e resistência à insulina (HOMA-IR). Resultados: observaram-se valores elevados de NHDL-c em 10 (3,7%) e presença de HDCV familiar precoce em 46 (17,1%) crianças. Houve fraca associação entre HDCV familiar e NHDL-c (Cramer’s-V-test = 0,120; p=0,050). Entre as crianças com NHDL-c ≥145 mg/dL, quatro (40%) tinham HDCV familiar. A presença de HDCV familiar não se associou com as variáveis estudadas. As variáveis que se associaram de forma independente com o NHDL-c ≥145 mg/dL foram HOMA-IR (OR=1,7; IC95% 1,1-2,6) e pressão arterial diastólica (OR=1,1; IC95% 1,02-1,2). Conclusão: os valores de NHDL-c se associaram com pressão arterial e resistência insulínica. HDCV familiar não se associou com outros fatores de risco clássicos para DCV, embora a frequência encontrada tenha sido quase cinco vezes superior à de NHDL-c elevado.

Polimorfismos de los genes LEP , LDLR , APOA4 y sus relaciones con el sobrepeso, la obesidad y el riesgo de enfermedades crónicas en adultos del estado Sucre, Venezuela / LEP , LDLR and APOA4 gene polymorphisms and their relationship with the risk of overweight, obesity and chronic diseases in adults of the State of Sucre, Venezuela

Introducción. La prevalencia del sobrepeso, la obesidad y algunas enfermedades crónicas no transmisibles ha aumentado; sus causas pueden ser genéticas, epigenéticas o ambientales, por lo cual es importante evaluar la variabilidad en estas interacciones. Objetivo. Analizar las relaciones entre nueve polimorfismos de nucleótido simple de los genes LEP (rs2167270), LDLR (rs885765, rs688, rs5925, rs55903358, rs5742911) y APOA4 (rs5095, rs675, rs5110), y los fenotipos asociados al sobrepeso, la obesidad y otras enfermedades concomitantes. Materiales y métodos. Se evaluaron parámetros clínicos y antropométricos en 144 sujetos del estado Sucre, Venezuela, 76 hombres y 68 mujeres , con medias de edad de 29,93±8,29 y 32,49±11,15 años, respectivamente. Se hizo la genotipificación de los polimorfismos seleccionados mediante enzimas de restricción; se estudiaron las asociaciones entre genotipo y riesgo, y se compararon los promedios de las medidas antropométricas y bioquímicas previamente ajustadas a variables biológicas y ambientales. Resultados. Según el índice de masa corporal (IMC), el 38,9 % de los individuos tenía sobrepeso (25=IMC=29,9 kg/m 2 ) y el 20,1 %, obesidad (IMC=30 kg/m 2 ) . Las frecuencias genotípicas y alélicas de los grupos con un índice de masa corporal normal y uno alto (sobrepeso y obesidad) resultaron similares. Solo se encontró asociación entre el genotipo ancestral A/A del rs5742911 y el riesgo alto por los niveles de la lipoproteína de alta densidad o colesterol HDL (OR=2,944, IC 95% 1,446-5,996; p=0,003). La diferencia entre los promedios corregidos de colesterol HDL para los genotipos del rs5742911 resultó significativa (p=0,005) (A/A: 41,50±14,81 mg/dl; A/G: 45,00±12,07 mg/dl; G/G: 47,17±9,43 mg/dl). Conclusión. En la mayoría de las variantes genéticas estudiadas, se registró la asociación con el sobrepeso y la obesidad de los genotipos ancestrales, aunque sin ser significativa. El polimorfismo rs5742911 podría resultar útil como indicador del riesgo de enfermedades crónicas.

Introduction: Overweight, obesity and some chronic diseases have become more prevalent recently. It is well known that their causes may be genetic, epigenetic, environmental, or a mixture of these. Objective: To analyze the relationship between nine single nucleotide polymorphisms of genes LEP (rs2167270) , LDLR (rs885765, rs688, rs5925, rs55903358, rs5742911) and APOA4 (rs5095, rs675, rs5110) with obesity-related phenotypes and other comorbidities. Material and methods: We recruited 144 adults (76 males and 68 females, with average ages of 29.93±8.29 and 32.49±11.15 years, respectively) in the State of Sucre, Venezuela. Clinical and anthropometric parameters were obtained. Genotype-risk associations were studied. We then compared the averages registered for anthropometric and biochemical variables previously adjusted for biological and environmental factors. Results: According to the body mass index, 38.9% of the individuals in the sample were overweight (25=BMI=29.9 kg/m 2 ) and 20.1% were obese (BMI=30 kg/m 2 ). Genotype and allele frequencies did not differ statistically for groups with normal and high body mass index (overweight plus obesity). The association between LDLR rs5742911 ancestral genotype A/A and high risk condition related to HDL-cholesterol was the only one found to be significant (OR=2.944, 95% CI: 1.446-5.996; p=0.003). The difference in adjusted mean HDL-cholesterol for LDLR rs5742911 genotypes was statistically significant (p=0.005) (A/A: 41.50±14.81 mg/dL; A/G: 45.00±12.07 mg/dL; G/G: 47.17±9.43 mg/dL). Conclusions: For most of the genetic variants studied, there was an association with the presence of overweight and obesity among ancestral genotype carriers, although this was not statistically significant. The rs5742911 polymorphism may be useful as an indicator of a risk of chronic diseases.

APOE and LDLR Gene Polymorphisms and Dyslipidemia Tracking. Rio de Janeiro Study / Polimorfismos dos Genes APOE e RLDL e Tracking de Dislipidemia em Jovens. Estudo do Rio de Janeiro

Background: Studies show an association between changes in apolipoprotein E (ApoE) and LDLR receptor with the occurrence of dyslipidemia. Objectives: To investigate the association between polymorphisms of the APOE (ε2, ε3, ε4) and LDLR (A370T) genes with the persistence of abnormal serum lipid levels in young individuals followed up for 17 years in the Rio de Janeiro Study. Methods: The study included 56 individuals (35 males) who underwent three assessments at different ages: A1 (mean age 13.30 ± 1.53 years), A2 (22.09 ± 1.91 years) and A3 (31.23 ± 1.99 years). Clinical evaluation with measurement of blood pressure (BP) and body mass index (BMI) was conducted at all three assessments. Measurement of waist circumference (WC) and serum lipids, and analysis of genetic polymorphisms by PCR-RFLP were performed at A2 and A3. Based on dyslipidemia tracking, three groups were established: 0 (no abnormal lipid value at A2 and A3), 1 (up to one abnormal lipid value at A2 or A3) and 2 (one or more abnormal lipid values at A2 and A3). Results: Compared with groups 0 and 1, group 2 presented higher mean values of BP, BMI, WC, LDL-c and TG (p < 0.01) and lower mean values of HDL-c (p = 0.001). Across the assessments, all individuals with APOE genotypes ε2/ε4 and ε4/ε4 maintained at least one abnormal lipid variable, whereas those with genotype ε2/ε3 did not show abnormal values (χ2 = 16.848, p = 0.032). For the LDLR genotypes, there was no significant difference among the groups. Conclusions: APOE gene polymorphisms were associated with dyslipidemia in young individuals followed up longitudinally from childhood. .

Fundamento: Estudos demonstram a associação de alterações da apolipoproteína E (APOE) e do receptor da RLDL com a ocorrência de dislipidemia. Objetivos: Investigar a associação entre polimorfismos dos genes da APOE (APOE - ε2, ε3, ε4) e do receptor da LDL (RLDL - A370T) com a persistência de alterações dos níveis lipídicos séricos em jovens acompanhados há 17 anos no Estudo do Rio de Janeiro. Métodos: Foram estudados 56 indivíduos (35 masculinos) em três avaliações realizadas em idades distintas: A1 – média de idade: 13,30 ± 1,53 anos; A2 – média de idade: 22,09±1,91 anos e A3 – média de idade: 31,23±1,99 anos. Nas três avaliações foram determinados a pressão arterial (PA) e o índice de massa corporal (IMC). Em A2 e A3 foram obtidos a circunferência abdominal (CA) e os lípides séricos, e analisados os polimorfismos genéticos por PCR-RFLP. Com base no tracking de dislipidemia, três grupos foram constituídos: 0 (nenhum lípide alterado em A2 e A3), 1 (até um lípide alterado em A2 ou A3) e 2 (um ou mais lípides alterados em A2 e A3). Resultados: Em comparação aos grupos 0 e 1, o grupo 2 apresentou maiores médias de PA, IMC, CA, LDL-c e TG (p < 0,01) e menor média de HDL-c (p = 0,001) que os grupos 0 e 1. Todos os indivíduos com genótipo APOE ε2/ε4 e ε4/ε4 mantiveram durante as avaliações pelo menos um lípide alterado, enquanto que aqueles com genótipo ε2/ε3 não apresentaram alterações (χ2=16,848, p = 0,032). Para os genótipos RLDL não houve diferença significativa entre os grupos. Conclusões: O polimorfismo do gene APOE se associou à presença de dislipidemia em indivíduos jovens em acompanhamento longitudinal desde a infância. .

Influence of PPARA, RXRA, NR1I2 and NR1I3 gene polymorphisms on the lipid-lowering efficacy and safety of statin therapy / Influência de polimorfismos nos genes PPARA, RXRA, NR1I2 e NR1I3 na eficácia hipolipemiante e na segurança da terapia com estatinas

OBJECTIVE: The aim of the present study was investigate the association between six genetic variants in the nuclear receptor genes PPARA, RXRA, NR1I2 and NR1I3 and the lipid-lowering efficacy and safety of statin therapy. SUBJECTS AND METHODS: The study was carried out on 240 Brazilian hypercholesterolemic patients on simvastatin and atorvastatin therapy. The polymorphisms were analyzed by PCR-based methods. RESULTS: The NR1I3 rs2307424 genotype distribution was different between subjects with and without adverse drug reactions. Among subjects in the ADR group, no T/T homozygotes were observed for this polymorphism, while in the non-ADR group the frequency of this genotype was 19.4% (P = 0.007, after multiple testing corrections P = 0.042). CONCLUSION: The polymorphisms investigated in PPARA (rs1800206), RXRA (rs11381416), and NR1I2 (rs1523130) did not influence the lipid-lowering efficacy and safety of statin. Our results show the possible influence of NR1I3 genetic variant on the safety of statin.

OBJETIVO: O objetivo deste estudo foi investigar a associação de seis variantes genéticas nos genes de receptores nucleares PPARA, RXRA, NR1I2 e NR1I3 na eficácia hipolipemiante e na segurança da terapia com estatinas. SUJEITOS E MÉTODOS: O estudo foi realizado com 240 pacientes hipercolesterolêmicos em terapia com sinvastina e atorvastatina. Os polimorfismos foram analisados por meio de métodos baseados em PCR. RESULTADOS: A distribuição da frequência genotípica do polimorfismo NR1I3 rs2307424 foi diferente entre os pacientes com e sem efeito adverso à medicação; entre os sujeitos do grupo com efeitos adversos, nenhum homozigoto T/T foi observado, enquanto no grupo de indivíduos sem efeitos adversos a frequência desse genótipo foi 19,4% (P = 0,007, após correção para múltiplos testes P = 0,042). CONCLUSÃO: Os polimorfismos investigados nos genes PPARA (rs1800206), RXRA (rs11381416) e NR1I2 (rs1523130) não foram associados com eficácia hipolipemiante e segurança da terapia com estatinas. Nossos resultados mostram uma possível influência de variantes do gene NR1I3 (rs2307424) no desenvolvimento de efeitos adversos à terapia com estatinas.

Prevalência de dislipidemia em adultos de meia-idade com polimorfismo do gene NOS3 e baixa aptidão cardiorrespiratória / Prevalence of dyslipidemia in middle-aged adults with NOS3 gene polymorphism and low cardiorespiratory fitness

OBJETIVO: Analisar a influência da associação dos polimorfismos do gene da sintase do óxido nítrico endotelial (NOS3) para as posições -786T>C, Glu298Asp e íntron 4b/a e a aptidão cardiorrespiratória sobre as concentrações de nitrito/nitrato, pressão arterial, perfil lipídico e prevalência de doenças cardiometabólicas em adultos. SUJEITOS E MÉTODOS: Noventa e duas pessoas foram divididas de acordo com o genótipo: não polimórficas (NP) e polimórficas (P). Posteriormente, foram subdivididas pela aptidão cardiorrespiratória associada ao genótipo: alta (ANP e AP) ou baixa (BNP e BP). RESULTADOS: Os indivíduos que apresentavam polimorfismo para as posições Glu298Asp+Íntron 4b/a e Glu298Asp+-786T>C e baixa aptidão cardiorrespiratória apresentaram maiores valores de colesterol total e maior prevalência de dislipidemia. CONCLUSÃO: Nossos dados demonstram que os polimorfismos do gene da NOS3 para essas duas associações influenciam os níveis de colesterol plasmático, e essa associação foi mais claramente observada quando os indivíduos apresentavam menor nível de aptidão cardiorrespiratória.

OBJECTIVE: To evaluate the influence of the interaction between endothelial nitric oxide synthase gene (NOS3) polymorphisms at positions -786T>C, Glu298Asp and intron 4b/a, and cardiorespiratory fitness on plasma nitrite/nitrate levels, blood pressure, lipid profile, and prevalence of cardiometabolic disorders. SUBJECTS AND METHODS: Ninety-two volunteers were genotyped for NOS3 polymorphisms at positions (-786T>C and Glu298Asp) and (intron 4b/a) and divided according to the genotype: non-polymorphic (NP) and polymorphic (P). After that, they were subdivided according to the cardiorespiratory fitness associated with genotype: high (HNP and HP) and low (LNP and LP). RESULTS: The subjects with polymorphism for the interactions at positions Glu298Asp + intron 4b/a, and Glu298Asp+-786T>C showed the highest values in total cholesterol, as well as dyslipidemia. CONCLUSION: Our findings show that NOS3 gene polymorphisms at positions -786T>C, Glu298Asp, and intron 4b/a exert negative effects on the lipid profile compared with those who do not carry polymorphisms.

Colaboraciones exitosas entre tres instituciones mexicanas en el estudio de las dislipidemias, la obesidad y la diabetes / Succesful collaborations between three Mexican institutions for research on dislipidemias, obesity and diabetes

Objetivo: Describir las contribuciones de tres instituciones mexicanas (Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Universidad Nacional Autónoma de México y Centro de Encuestas Nacionales de Salud del Instituto Nacional de Salud Pública) en el estudio de las enfermedades crónico-degenerativas. Resultados: Entre las aportaciones destacan la descripción de un alelo de riesgo para tener diabetes y el síndrome metabólico (R230C del transportador ABC-A1) específico para la población mexicana, una herramienta para estimar la probabilidad de tener diabetes a siete años, la descripción de la epidemiología molecular de la hipercolesterolemia familiar en adultos mexicanos y la identificación de varias regiones cromosómicas asociadas con la hiperlipidemia familiar combinada, así como la contribución a la descripción de la epidemiología de la diabetes, el síndrome metabólico y las dislipidemias en nuestro país. Conclusiones: La conjunción de intereses y la visión complementaria de los investigadores de las tres instituciones han hecho posible una serie de colaboraciones exitosas. La información generada será de utilidad para el desarrollo de pruebas diagnósticas y para la planeación de programas preventivos.

OBJECTIVE: To describe the contributions ofthree Mexican institutions (Instituto Nacional de Ciencias Médicas y Nutrición [quot ]Salvador Zubirán[quot ], Universidad Nacional Autónoma de México and the Centro de Encuestas Nacionales de Salud of the Instituto Nacional de Salud Pública) in the study, of chronic degenerative disorders. RESULTS: The most relevant group contributions include: the identification of a risk allele for metabolic syndrome and diabetes, specific for the Mexican population (the R230C variant of the ABC-A1 transporter); the design and validation of a population-based definition of metabolic syndrome which is useful to predict the risk of incident diabetes; the description of the molecular epidemiology of familial hypercholesterolemia in Mexico and the identification of several loci associated with familial combined hyperlipidemia. In addition, members of these institutions have participated in the description of the epidemiology of diabetes, metabolic syndrome and lipid abnormalities. CONCLUSIONS: The complementary approach of these research groups has facilitated successful collaborations. Our results will be useful for the future development of diagnostic tests and preventive programs.

Apolipoprotein E polymorphism in Brazilian dyslipidemic individuals: Ouro Preto study

The influence of apolipoprotein E alleles and genotypes on plasma lipid levels was determined in 185 individuals of mixed ethnicity living in Ouro Preto, Brazil. DNA was obtained from blood samples and the genotypes were determined by an RFLP-PCR procedure. The *3 allele was the most frequent (72 percent), followed by *4 (20 percent) and *2 (8 percent); *4 frequency was higher and *2 frequency was lower in the dyslipidemic group than in the normal control group. The *2 carriers presented lower LDL and total cholesterol levels compared to the *3 and *4 carriers. All six expected genotypes were observed in the individuals genotyped: E2/2 (2.1 percent), E4/4 (2.7 percent), E2/4 (3.7 percent), E2/3 (8.0 percent), E3/3 (53.3 percent), E3/4 (29.9 percent); no difference in genotype frequencies was found between the normal and dyslipidemic groups. Compared with *2, the presence of *3 increases more than two times the risk for dyslipidemia (OR = 2.31; P = 0.025; 95 percent CI = 1.06-5.06) and the presence of *4 increases it three times (OR = 3.31; P = 0.006; 95 percent CI = 1.36-8.04). The only significant effect of genotype was an increased risk for dyslipidemia in the *4 genotype carriers (E3/4 + E4/4) compared with the *2 genotype carriers (E2/2 + E2/3) with OR = 3.69 (95 percent CI = 1.25-10.88). The present study indicates that in the Ouro Preto admixed population the presence of APOE *2 can confer a protective effect, whereas the presence of APOE *4 implies an enhanced risk for dyslipidemia.

Perfil lipídico e efeitos da orientação nutricional em adolescentes com história familiar de doença arterial coronariana prematura / Lipid profile and nutrition counseling effects in adolescents with family history of premature coronary artery disease

OBJETIVO: Examinar o perfil lipídico e parâmetros nutricionais de adolescentes com história familiar de doença arterial coronariana (DAC) prematura e avaliar os efeitos da orientação nutricional. MÉTODOS: O estudo incluiu 48 adolescentes de ambos os sexos e idades entre 10 e 19 anos (grupo caso, n=18; grupo controle, n=30). RESULTADOS: Os filhos de coronarianos jovens apresentaram valores mais elevados de colesterol total (189 ± 30 vs. 167 ± 26 mg/dl, p<0,01), LDL-C (144 ± 20 vs. 100 ± 27 mg/dl, p<0,001) e Apo B (80 ± 15 vs. 61 ± 18 mg/dl, p=0,001) e valores mais baixos de HDL-C (45 ± 9 vs. 51 ± 13 mg/dl, p<0,02) que os jovens controles. Não se observaram diferenças para os triglicérides e Apo A-I. Com a orientação dietoterápica obteve-se redução no consumo alimentar de ácidos graxos saturados (pré: 15,5 ± 4,7 por cento vs. pós: 6,6 ± 3,7 por cento, p=0,003) e melhora no perfil lipídico: CT (-8 por cento, p=0,033), LDL-C (-18,2 por cento, p=0,001), TG (-53 por cento, p=0,002) nos filhos de pacientes com DAC prematura que apresentavam hiperlipidemia. CONCLUSÃO: A presença de dislipidemia foi mais prevalente em adolescentes filhos de portadores de DAC prematura, mas foi responsiva à intervenção nutricional.