RESUMO
BACKGROUND AND AIMS: Diabetic kidney disease (DKD) is associated with lipid derangements that worsen kidney function and enhance cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications, bringing up the participation of nontraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in the HDL proteome and functionality. The HDL composition, proteome, chemical modification and functionality were analyzed in nondialysis subjects with DKD categorized according to the estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). METHODS: Individuals with DKD were divided into eGFR> 60 mL/min/1.73 m2 plus AER stages A1 and A2 (n = 10) and eGFR< 60 plus A3 (n = 25) and matched by age with control subjects (eGFR> 60; n = 8). RESULTS: Targeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more highly expressed in the eGFR< 60 + A3 group than in the controls: apolipoprotein D (apoD) and apoA-IV. HDL from the eGFR< 60 + A3 group presented higher levels of total AGEs (20%), pentosidine (6.3%) and carbamoylation (4.2 x) and a reduced ability to remove 14C-cholesterol from macrophages (33%) in comparison to HDL from controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups, but HDL from the eGFR< 60 + A3 group presented a greater ability to inhibit the secretion of IL-6 and TNF-alpha (95%) in LPS-elicited macrophages in comparison to the control group. CONCLUSION: The increase in apoD and apoA-IV could contribute to counteracting the HDL chemical modification by AGEs and carbamoylation, which contributes to HDL loss of function in well-established DKD.
Assuntos
Apolipoproteínas A/sangue , Apolipoproteínas D/sangue , Nefropatias Diabéticas/sangue , Lipoproteínas HDL/sangue , Proteoma/metabolismo , Idoso , Idoso de 80 Anos ou mais , Albuminúria/sangue , Albuminúria/genética , Albuminúria/patologia , Apolipoproteínas A/genética , Apolipoproteínas D/genética , Arginina/análogos & derivados , Arginina/sangue , Arginina/genética , Estudos de Casos e Controles , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Feminino , Expressão Gênica , Taxa de Filtração Glomerular , Produtos Finais de Glicação Avançada/sangue , Produtos Finais de Glicação Avançada/genética , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Rim/metabolismo , Rim/patologia , Lipopolissacarídeos/farmacologia , Lipoproteínas HDL/genética , Lisina/análogos & derivados , Lisina/sangue , Lisina/genética , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células , Carbamilação de Proteínas , Proteoma/classificação , Proteoma/genética , Diálise Renal , Fatores de Risco , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
INTRODUCTION Hypertension is one of the most studied risk factors for cardiovascular disease in adults; in children and adolescents, its global prevalence changes with age, from 1%-3% in children to 3.2% in adolescents. In adults, in addition to hypertension, several biochemical markers of cardiovascular risk have been identified. Confirming an association between these and hypertension in childhood and adolescence would allow for more timely diagnosis and monitoring of cardiovascular disease, since the presence of both the markers and hypertension would imply increased risk. OBJECTIVE Confirm an association between biochemical risk markers of cardiovascular disease and hypertension in children aged 8 to 11 years. METHODS A cross-sectional study of 373 children aged 8-11 years was conducted in 3 primary schools in the city of Santa Clara in central Cuba. The variables examined were age, sex, height, blood pressure, cholesterol, triglycerides, lipoproteins and apolipoproteins. The children were classified as normotensive, prehypertensive or hypertensive, based on blood pressure readings and percentiles for age, sex and height. Descriptive statistics were calculated for quantitative variables. A bivariate analysis, tests of independence for qualitative variables and a means comparison for quantitative variables (ANOVA and its nonparametric alternative, the Kruskal Wallis test) were performed. Fisher's F-test and its associated probability value were employed. RESULTS Some 32.2% of the children were prehypertensive and 5.1% hypertensive. Cholesterol and triglyceride values were significantly higher in hypertensive than in normotensive children (p = 0.028 and p = 0.047, respectively). HDL numbers were higher in normotensive children (p =0.001), and LDL numbers and the LDL/HDL ratio were higher in the hypertensive children, with differences between groups (p = 0.001 for both variables). There were differences between the three blood pressure categories for lipoprotein(a) and ApoA (p <0.001 and p = 0.001), for ApoB and for the ApoB/ApoA ratio (p <0.001 for both variables), with lower ApoA values and higher ApoB and ApoB/ApoA values in the hypertensive children. CONCLUSIONS The biochemical risk markers most strongly associated with hypertension in children are ApoB values, LDL, lipoprotein(a), and LDL/HDL and ApoB/ApoA ratios. KEYWORDS Adolescent, child, hypertension, apolipoproteins, cardiovascular diseases, risk factors, Cuba.
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Biomarcadores/sangue , Hipertensão/sangue , Antropometria , Apolipoproteína B-100/sangue , Apolipoproteínas A/sangue , Doenças Cardiovasculares/sangue , Criança , Colesterol/sangue , Estudos Transversais , Cuba/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , MasculinoRESUMO
The aim of the study was to describe biomarkers of lipid metabolism associated with increased cardiovascular risk and their correlation with disease variables and markers of inflammation in adolescent females with systemic lupus erythematosus (SLE). This cross-sectional controlled study evaluated 33 adolescent females with juvenile SLE and 33 healthy controls. Anthropometric data, SLE disease activity index (SLEDAI), medications, proteinuria, ultra-sensitive C-reactive protein (us-CRP), lipid profile (total cholesterol, LDL-c, HDL-c and triglycerides), apolipoproteins A and B (Apo A-I and B), paraoxonase, and myeloperoxidase were evaluated. Median age of the patients and the median disease duration were 16.7 years and 54 months, respectively. SLEDAI scores above 4 were observed in 11 (33.3 %) patients. Moreover, 12 (36.4 %) patients were overweight, and 5 (15.2 %) had low height for age ratios. Dyslipidemia was observed in 13 (39.4 %) patients and in 7 (21.2 %) controls with a decrease in HDL-c concentrations in SLE patients even after adjustment for their nutritional status. In the group with SLE, us-CRP concentrations were inversely correlated with LDL-c/ApoB ratio (p = 0.031). After multivariate regression analysis, the SLE group showed lower concentration of Apo A-I and a decreased LDL-c/ApoB ratio. SLE adolescent females with low disease activity, with preserved kidney function and on low dose of corticosteroids, regardless of nutritional status and food intake, have proatherogenic lipid biomarkers, which may contribute to an increased atherosclerotic risk.
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Colesterol/sangue , Metabolismo dos Lipídeos/fisiologia , Lúpus Eritematoso Sistêmico/sangue , Triglicerídeos/sangue , Adolescente , Apolipoproteínas A/sangue , Apolipoproteínas B/sangue , Aterosclerose/sangue , Aterosclerose/etiologia , Biomarcadores/sangue , Criança , Estudos Transversais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Bariatric surgery usually leads to improvement on the general lipid profile, but its role in the levels of apolipoprotein A-IV (Apo-AIV) is not completely understood. Apo-AIV is a gut-released lipoprotein which is enrolled in satiety regulation and presents anti-inflammatory, anti-atherogenic, and anti-oxidative properties. The objective of this study was to determine the influence of biliopancreatic diversion (BPD) in the levels of Apo-AIV. METHODS: This is a prospective exploratory study which evaluated eight obese individuals with type 2 diabetes mellitus (T2DM) who underwent BPD (Scopinaro operation) and were followed-up for 12 months. Apo-AIV levels were determined by means of serial dosages through a standard meal tolerance test (MTT) in the immediate preoperative period and then 12 months later. RESULTS: There was a significant change in the Apo-AIV curve following MTT before and after surgery. At 0 and 45 min, the Apo-AIV levels did not significantly differ before and after surgery; at 120 and 180 min, Apo-AIV levels were significantly lower following BPD. CONCLUSIONS: We observed a decrease of postprandial levels of Apo-AIV following MTT in mildly obese individuals with T2DM. This finding appears to be related to the suppression in the Apo-AIV response that obese individuals tend to present. Weight reduction itself, endotoxemia, and the large segments of bypassed intestine may be enrolled in this impaired response.
Assuntos
Apolipoproteínas A/sangue , Desvio Biliopancreático , Diabetes Mellitus Tipo 2/cirurgia , Obesidade/cirurgia , Adulto , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Período Pós-Prandial/fisiologia , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Diet is an important environmental factor that interacts with genes to modulate the likelihood of developing disorders in lipid metabolism and the relationship between diet and genes in the presence of other chronic diseases such as obesity. The objective of this study was to analyze the interaction of a high fat diet with the APOA2 (rs3813627 and rs5082), APOA5 (rs662799 and rs3135506) and LEPR (rs8179183 and rs1137101) polymorphisms and its relationship with obesity and dyslipidemia in young subjects. METHODS: The study included 200 young subjects aged 18 to 25 years (100 normal-weight and 100 obese subjects). Dietary fat intake was measured using the frequency food consumption questionnaire. Genotyping of polymorphisms was performed by PCR-RFLP. RESULTS: Individuals carrying the APOA5 56 G/G genotype with a high saturated fatty acid consumption (OR = 2.7, p = 0.006) and/or total fat (OR = 2.4, p = 0.018), associated with an increased risk of obesity. We also found that A/G + G/G genotypes of the 668 A/G polymorphism in the LEPR gene with an intake ≥ 12 g/d of saturated fatty acids, have 2.9 times higher risk of obesity (p = 0.002), 3.8 times higher risk of hypercholesterolemia (p = 0.002) and 2.4 times higher risk of hypertriglyceridemia (p = 0.02), than those with an intake <12 g/d of saturated fatty acids. Similarly, LEPR 668 A/G + G/G carriers with a high fat total intake had 3.0 times higher risk of obesity (p = 0.002) and 4.1 times higher risk of hypercholesterolemia (p = 0.001). CONCLUSION: Our results suggest that dietary fat intake modifies the effect of APOA5 and LEPR polymorphisms on serum triglycerides, cholesterol levels and obesity in young subjects.
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Apolipoproteína A-II/genética , Apolipoproteínas A/genética , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/efeitos adversos , Dislipidemias/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Apolipoproteína A-II/sangue , Apolipoproteína A-V , Apolipoproteínas A/sangue , Glicemia/metabolismo , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/etiologia , Dislipidemias/patologia , Jejum , Ácidos Graxos/sangue , Feminino , Expressão Gênica , Genótipo , Humanos , Masculino , Obesidade/sangue , Obesidade/etiologia , Obesidade/patologia , Receptores para Leptina , Risco , Inquéritos e Questionários , Triglicerídeos/sangueRESUMO
BACKGROUND: Diets are the important players in regulating plasma lipid profiles. And the R219K polymorphism at the gene of ATP-binding cassette transporter 1(ABCA1) was reported to be associated with the profiles. However, no efforts have been made to investigate the changes of lipid profiles after a high-carbohydrate and low-fat diet in different subjects with different genotypes of this polymorphism. This study was to evaluate the effects of ABCA1 R219K polymorphism on serum lipid and apolipoprotein (apo) ratios induced by a high-carbohydrate/low-fat (high-CHO) diet. After a washout diet of 54.1% carbohydrate for 7 days, 56 healthy young subjects (22.89 ± 1.80 years old) were given a high-CHO diet of 70.1% carbohydrate for 6 days. Height, weight, waist circumference, hip circumference, glucose (Glu), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apoA-1 and apoB-100 were measured on the 1st, 8th and 14th days of this study. Body mass index (BMI), waist-to-hip ratios (WHR), log(TG/HDL-C), TC/HDL-C, LDL-C/HDL-C and apoA-1/apoB-100 were calculated. ABCA1 R219K was analyzed by a PCR-RFLP method. RESULTS: The results indicate that the male subjects of all the genotypes had higher WHR than their female counterparts on the 1st, 8th and 14th days of this study. The male K carriers had higher log(TG/HDL-C) and TC/HDL-C than the female carriers on the 1st and 14th days, and higher LDL-C/HDL-C on the 14th day. When compared with that on the 8th day, TC/HDL-C was decreased regardless of the genotypes and genders on the 14th day. Log(TG/HDL-C) was increased in the males with the RR genotype and the female K carriers. Lowered BMI, Glu and LDL-C/HDL-C were found in the male K carriers, but only lowered BMI in the female K carriers and only lowered LDL-C/HDL-C in the females with the RR genotype. CONCLUSIONS: These results suggest that ABCA1 R219K polymorphism is associated differently in males and females with elevated log(TG/HDL-C) and decreased LDL-C/HDL-C induced by the high-CHO diet.
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Transportadores de Cassetes de Ligação de ATP/genética , Apolipoproteínas/sangue , Colesterol/sangue , Dieta com Restrição de Gorduras , Carboidratos da Dieta/metabolismo , Polimorfismo Genético/fisiologia , Adulto , Alelos , Apolipoproteína B-100/sangue , Apolipoproteínas A/sangue , Glicemia/análise , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Genótipo , Humanos , Masculino , Metaboloma/genética , Fatores Sexuais , Triglicerídeos/sangue , Adulto JovemRESUMO
BACKGROUND: Diets are the important players in regulating plasma lipid profiles. And the R219K polymorphism at the gene of ATP-binding cassette transporter 1(ABCA1) was reported to be associated with the profiles. However, no efforts have been made to investigate the changes of lipid profiles after a high-carbohydrate and low-fat diet in different subjects with different genotypes of this polymorphism. This study was to evaluate the effects of ABCA1 R219K polymorphism on serum lipid and apolipoprotein (apo) ratios induced by a high-carbohydrate/low-fat (high-CHO) diet. After a washout diet of 54.1% carbohydrate for 7 days, 56 healthy young subjects (22.89 ± 1.80 years old) were given a high-CHO diet of 70.1% carbohydrate for 6 days. Height, weight, waist circumference, hip circumference, glucose (Glu), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apoA-1 and apoB-100 were measured on the 1st, 8th and 14th days of this study. Body mass index (BMI), waist-to-hip ratios (WHR), log(TG/HDL-C), TC/HDL-C, LDL-C/HDL-C and apoA-1/apoB-100 were calculated. ABCA1 R219K was analyzed by a PCR-RFLP method. RESULTS: The results indicate that the male subjects of all the genotypes had higher WHR than their female counterparts on the 1st, 8th and 14th days of this study. The male K carriers had higher log(TG/HDL-C) and TC/HDL-C than the female carriers on the 1st and 14th days, and higher LDL-C/HDL-C on the 14th day. When compared with that on the 8th day, TC/HDL-C was decreased regardless of the genotypes and genders on the 14th day. Log(TG/HDL-C) was increased in the males with the RR genotype and the female K carriers. Lowered BMI, Glu and LDL-C/HDL-C were found in the male K carriers, but only lowered BMI in the female K carriers and only lowered LDL-C/HDL-C in the females with the RR genotype. CONCLUSIONS: These results suggest that ABCA1 R219K polymorphism is associated differently in males and females with elevated log(TG/HDL-C) and decreased LDL-C/HDL-C induced by the high-CHO diet.
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Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Transportadores de Cassetes de Ligação de ATP/genética , Apolipoproteínas/sangue , Colesterol/sangue , Dieta com Restrição de Gorduras , Carboidratos da Dieta/metabolismo , Polimorfismo Genético/fisiologia , Alelos , /sangue , Apolipoproteínas A/sangue , Glicemia/análise , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Genótipo , Metaboloma/genética , Fatores Sexuais , Triglicerídeos/sangueRESUMO
BACKGROUND: The Mexican population and others with Amerindian heritage exhibit a substantial predisposition to dyslipidemias and coronary heart disease. Yet, these populations remain underinvestigated by genomic studies, and to date, no genome-wide association (GWA) studies have been reported for lipids in these rapidly expanding populations. METHODS AND FINDINGS: We performed a two-stage GWA study for hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) in Mexicans (n=4361), and identified a novel Mexican-specific genome-wide significant locus for serum triglycerides (TGs) near the Niemann-Pick type C1 protein gene (p=2.43×10(-08)). Furthermore, three European loci for TGs (APOA5, GCKR and LPL), and four loci for HDL-C (ABCA1, CETP, LIPC and LOC55908) reached genome-wide significance in Mexicans. We used cross-ethnic mapping to narrow three European TG GWA loci, APOA5, MLXIPL, and CILP2 that were wide and contained multiple candidate variants in the European scan. At the APOA5 locus, this reduced the most likely susceptibility variants to one, rs964184. Importantly, our functional analysis demonstrated a direct link between rs964184 and postprandial serum apoAV protein levels, supporting rs964184 as the causative variant underlying the European and Mexican GWA signal. Overall, 52 of the 100 reported associations from European lipid GWA meta-analysis generalised to Mexicans. However, in 82 of the 100 European GWA loci, a different variant other than the European lead/best-proxy variant had the strongest regional evidence of association in Mexicans. CONCLUSIONS: This first Mexican GWA study of lipids identified a novel GWA locus for high TG levels; used the interpopulation heterogeneity to significantly restrict three previously known European GWA signals, and surveyed whether the European lipid GWA SNPs extend to the Mexican population.
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Apolipoproteínas A/genética , Loci Gênicos/genética , Hipertrigliceridemia/genética , Hipoalfalipoproteinemias/genética , Indígenas Norte-Americanos/genética , Triglicerídeos/genética , Apolipoproteína A-V , Apolipoproteínas A/sangue , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Hipertrigliceridemia/etnologia , Hipoalfalipoproteinemias/etnologia , Desequilíbrio de Ligação , Proteínas de Membrana/genética , Proteínas de Membrana Transportadoras , México , Polimorfismo de Nucleotídeo Único/genética , Triglicerídeos/sangue , População Branca/genéticaRESUMO
OBJECTIVES: Associations of leisure-time physical activity (LTPA), commuting and total physical activity with inflammatory markers, insulin resistance and metabolic profile in individuals at high cardiometabolic risk were investigated. DESIGN: This was a cross-sectional study. METHODS: A total of 193 prediabetic adults were compared according to physical activity levels measured by the international physical activity questionnaire; p for trend and logistic regression was employed. RESULTS: The most active subset showed lower BMI and abdominal circumference, reaching significance only for LTPA (p for trend=0.02). Lipid profile improved with increased physical activity levels. Interleukin-6 decreased with increased total physical activity and LTPA (p for trend=0.02 and 0.03, respectively), while adiponectin increased in more active subsets for LTPA (p for trend=0.03). Elevation in adjusted OR for hypercholesterolemia was significant for lower LTPA durations (p for trend=0.04). High apolipoprotein B/apolipoprotein A ratio was inversely associated with LTPA, commuting and total physical activity. Increase in adjusted OR for insulin resistance was found from the highest to the lowest category of LTPA (p for trend=0.04) but significance disappeared after adjustments for BMI and energy intake. No association of increased C-reactive protein with physical activity domains was observed. CONCLUSIONS: In general, the associations of LTPA, but not commuting or total physical activity, with markers of cardiometabolic risk reinforces the importance of initiatives to increase this domain in programs for the prevention of lifestyle-related diseases.