The -384A >C polymorphism of endothelial lipase gene promoter region in Chinese healthy normolipidemic and endogenous hypertriglyceridemic subjects / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the effects of the -384A>C polymorphism in the promoter region of endothelial lipase (EL) gene on serum lipid and apolipoprotein levels in healthy normolipidemic (HTG) and endogenous hypertriglyceridemic (HTG) subjects.</p><p><b>METHODS</b>Two hundred and fourteen healthy normolipidemic and 103 endogenous hypertriglyceridemic subjects from a population of Chinese Han nationality in Chengdu area were studied using restriction fragment length polymorphism (RFLPs). Serum lipids were measured by enzymatic kits and apolipoproteins AI, AII, B100, CII, CIII and E were measured by the radial immunadiffussion kits.</p><p><b>RESULTS</b>The frequency of the C allele at the -384A>C site in EL gene in the population (0.178) was higher than that of Japanese population (0.119) and Japanese Americans (0.115) (P < 0.01 and P < 0.01), respectively. No significant difference between normolipidemic and HTG groups was found in both allele and genotype frequencies. In normal group, subjects of the C allele carriers (A/C and C/C genotype carriers) had a higher serum mean concentration of TC, LDL-C and nHDL-C when compared with those of genotype AA (5.23 +/- 0.74 mmol/L vs 4.93 +/- 0.74 mmol/L, P=0.025; 3.27 +/- 0.74 mmol/L vs 2.98 +/- 0.80 mmol/L, P=0.038; 3.81 +/- 0.73 mmol/L vs 3.49 +/- 0.85 mmol/L, P=0.031, respectively). Similar result was only observed in female subgroup when male and female subgroups were further separated. No significant changes of lipid and lipoprotein levels were observed in the polymorphism in HTG group.</p><p><b>CONCLUSION</b>These results suggest that the -384A>C polymorphism in the promoter region of the endothelial lipase gene is associated with serum TC, LDL-C, and nHDL-C levels in healthy Chinese subjects in Chengdu area, but not associated with the lipid levels in the endogenous hypertriglyceridmic group.</p>

APOA1/C3/A4 gene cluster variability and lipid levels in Brazilian children

Genetic studies have suggested that polymorphisms of genes coding for apolipoproteins are significant determinants of serum lipoprotein and lipid levels in adults. However, only a few studies have investigated the association of these polymorphisms in children. Therefore, in the present investigation we studied the distribution of APOA1 -75 G>A, +83 C>T, APOC3 -482 C>T, -455 T>C and 3238 C>G, and APOA4 Q360H and T347S polymorphisms and their influence on plasma lipoprotein levels in children from a Brazilian northeastern admixed population. The seven polymorphic sites were genotyped in 414 children aged 5 to 15 years (mean 8.9 ± 2.9). The genotypes of the seven polymorphic sites were assessed by PCR-RFLP methods. The frequencies of the less common alleles were, in general, intermediate among parental populations, as expected. Strong linkage disequilibrium was detected between polymorphisms at the APOA1, APOC3 and APOA4 loci in this admixed population sample. Overall the genotype effects seen in adults were weaker or absent in children. The APOC3/-455 and APOA4 T347S variants showed significant effects on HDL cholesterol in girls (P = 0.033 and P = 0.016, respectively). Significantly higher plasma total (P = 0.003) and LDL cholesterol (P = 0.004) levels were observed in boys who were carriers of the 3238G allele at the APOC3/3238 C>G site. These results disclosed an overall absence of associations between these polymorphisms and lipids in children. This finding is not unexpected because expression of the effect of these polymorphisms might depend on the interaction with environmental variables both internal and external to the individual.

Mitochondrial cytochrome C and ultrastructural changes in hepatic steatosis induced by hepatitis C virus

Hepatic steatosis is an important hallmark of hepatitis C virus [HCV] infection. There is substantial body of evidence to implicate steatosis in the development of hepatic fibrosis. The underlying mechanisms of HCV-related steatosis however are not yet clarified. This study was performed to evaluate ultrastructural mitochondrial changes in patients with HCV-induced hepatic steatosis and correlate these findings with serum cytochrome c and apolipoproteins. Thirty-seven HCV-positive patients admitted to Theodore-Bilharz Research Institute were selected. They did not have other confounding prosteatogenic variables: diabetes, overweight, alcohol consumption and prosteatogenic drugs as amiodarone; corticosteroids. In addition, 10 apparently age- matched subjects were selected as a reference group. All subjects were initially subjected to full history, thorough clinical examination, liver function tests; lipid profile, HCV-IgG antibody and hepatitis-B surface antigen. All patients were subjected to ultrasound-guided liver biopsy. Biopsy specimen was processed for light and electron microscopic histopathological examination. According to histopathological findings, patients were divided into 4 groups according to the stage of fibrosis[I, II, III and IV]into :-Group 1 [n=7]; Group 2 [n=9]; Group:3 [n=9] and Group 4 [n=12]or cirrhotic group respectively. Measurement of apolipoproteins A, B and II and specific estimation of serum cytochrome-C was performed. Interpretation of the results revealed accumulated fat droplets by ultrastructure identification in the hepatocytes together with hypobetalipoproteinemia and hypotriglyceridemia. This was accompanied with mitochondrial ultrastructural alterations in all the studied groups ranging from complete dissolution to loss of outer mitochondria] membrane. In addition, it is noteworthy that ultrastructural changes of the rough endoplasmic reticulum [RER] detected in this study may be a contributing factor to abnormal fat metabolism in HCV. Concomittantly, serum cytochrome c was significantly lowered in all the studied groups as compared to the reference mean value. Depletion of mitochondria] cytochrme c might result in accumulation of reactive oxygen species and further accentuation of steatosis. There was significant correlation between serum cytochrome c, apolipoprotein B and serum triglycerides in the patients' group, ushering that it might have its role in HCV-induced lipid changes. In the cirrhotic group, ultrastructural elucidation of homogenous unlocalized intracytoplasmic fat and evident intracytoplasmic collagen fibrils was reported in this study. This was associated with significantly lowered serum ApoAl, ApoB and triglycerides as compared to all other groups. The afore-mentioned data solidifies the evidence that hepatic steatosis and fibrosis are important sequence of HCV infection and confirm the ability of hepatocyte to synthesize collagen. Moreover, the discerned intracytoplasmic unsaturated fat droplets might mirror the inability of the HCV-dysfunctioning hepatocyte to cope with the excessive dietary intake of fat and hence accentuation of steatosis results. In conclusion, ultrastructural. mitochondrial and RER changes seems to confirm their relation- to the associated intracytoplasmic fatty acids accumulation, the decreased serum cytochrome c and apolipoproteins Al and B Moreover it confirms the cytopathic effect of HCV

Genetic association of apoE and apoCI gene polymorphisms with coronary heart disease / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the genetic association of apolipoprotein (apo) E and apoCI gene polymorphisms with coronary heart disease (CHD) in China.</p><p><b>METHODS</b>apoE genotypes were identified by multiplex amplification refractory mutation system (multi-ARMS) and the apoCI promoter polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 186 cases with CHD (age: 65.0 +/- 10.5 years) and 350 controls (age: 63.6 +/- 8.3 years). The haplotype frequencies were estimated.</p><p><b>RESULTS</b>The frequencies of apoE E4/3 genotype (26.9%) and epsilon4 (14.5%) in CHD group were significantly higher than that in the control group (12.6%, 7.0%), P <0.05. The significant difference was also found for the apoCI locus and the CHD group showed higher rate of both for the H2 allele and genotypes, carrying this allele. Estimation of the haplotype frequencies indicated that the association between the apoE-CI haplotype and CHD was significantly strong. The apoE-epsilon4/apoCI-H2 was estimated to be responsible for 9.86% of CHD.</p><p><b>CONCLUSION</b>When the subjects carrying both epsilon4 and H2 alleles, they would have higher risk of suffering from CHD than controls.</p>

Factores de riesgo causales, condicionales y predisponentes en coronarios del sur argentino: asociación con la presencia y severidad de las lesiones demostradas por angiografía / Causal, conditional and predisposing risk factors in coronary subjects of south argentina: association with the presence and severity of the lesions demostrated by angiography

El objetivo de éste estudio fue determinar, en sujetos coronarios de ésta región, los factores de riesgo más frecuentes, categorizados en causales, condicionales y predisponentes, asociados con la presencia y severidad de enfermedad coronaria, demostrada por angiografía, y analizar la asociación del índice Apo B/C-HDL con la presencia y severidad de las lesiones. Se estudiaron 90 pacientes de 36 a 70 años de edad (64 varones y 26 mujeres) del Servicio de Hemodinamia del Hospital Privado del Sur a quienes se les realizó una cinecoronarioangiografía. Se obtuvieron datos clínicos y bioquímicos de cada paciente. Se analizaron dos grupos: controles (N=26), angiografías sin anormalidades o estenosis < 50 por ciento en un vaso, y coronarios (N=64), estenosis >= 50 por ciento y lesiones de distinta severidad en uno o varios vasos. Los factores de riesgo más frecuentes en coronarios vs. controles fueron: causales: hiperlipoproteinemias tratadas (P < 0,0007), diabetes mellitus Tipo 2 (P < 0,001), C-HDL < 35 mg/dl (P=0,016), hipertensión arterial o tratados (P < 0,02), ex-fumadores > 10/día (P < 0,04). Predisponentes: historia familiar (P < 0,0007), índice de conicidad > 1,24 (P < 0,005). Los índices, Apo B/C-HDL > 2,6, CT/C-HDL > 4,5, C-LDL/C-HDL > 3,0, P= 0,0049, P= 0,011 y P= 0,022, respectivamente. Los predictores de presencia de la enfermedad fueron (por análisis de regresión logística múltiple), hiperlipoproteinemias tratadas, Apo B/C-HDL > 2,6 o ambas, la historia familiar y el índice de conicidad. Los predictores de severidad fueron: la diabetes, hiperlipoproteinemias tratadas, Apo B/C-HDL > 2,6 o ambas, ex-fumadores > 10/día y la historia familiar...

Genetic variation of the Apo Al-CIII-AIV gene cluster in hypertriglyceridemic patients with chronic renal failure undergoing hemodialysis

Many patients with chronic renal failure (CRF) requiring hemodialysis present with hypertriglyceridemia (HTG). But the exact cause of HTG in CRF is still unknown. Genetic variation of the apo AI-CIII-AIV gene cluster was reported to be associated with primary HTG, atherosclerosis and coronary artery disease. This study was designed to evaluate the association between the restriction fragment length polymorphism (RFLP) of the apo AI-CIII-AIV gene cluster and HTG in patients with CRF undergoing hemodialysis. Genetic variations of the apo AI-CIII-AIV gene cluster were analysed in peripheral leukocyte samples from 59 patients with CRF undergoing hemodialysis: 17 patients with HTG (CRF-HTG) and 42 patients without HTG (CRF-NTG). The RFLP was achieved through the digestion of PCR products by two restriction enzymes, SstI and MspI. The frequency of SstI minor allele (S2) in CRF-HTG was 0.44, which was significantly higher than that in CRF-NTG (0.17). Frequencies of MspI minor allele (M2) in CRF-HTG and CRF-NTG were not significantly different (0.5 vs 0.32) (p=0.07). Frequencies of S2-M2 genotype were 0.65 in CRF-HTG, and 0.27 in CRF-NTG (p>0.005). These data indicate that genetic variation of the apo AI-CIII-AIV gene cluster may serve as one of the causes of HTG in CRF.

Genetic variation of the Apo Al-CIII-AIV gene cluster in hypertriglyceridemic patients with chronic renal failure undergoing hemodialysis

Many patients with chronic renal failure (CRF) requiring hemodialysis present with hypertriglyceridemia (HTG). But the exact cause of HTG in CRF is still unknown. Genetic variation of the apo AI-CIII-AIV gene cluster was reported to be associated with primary HTG, atherosclerosis and coronary artery disease. This study was designed to evaluate the association between the restriction fragment length polymorphism (RFLP) of the apo AI-CIII-AIV gene cluster and HTG in patients with CRF undergoing hemodialysis. Genetic variations of the apo AI-CIII-AIV gene cluster were analysed in peripheral leukocyte samples from 59 patients with CRF undergoing hemodialysis: 17 patients with HTG (CRF-HTG) and 42 patients without HTG (CRF-NTG). The RFLP was achieved through the digestion of PCR products by two restriction enzymes, SstI and MspI. The frequency of SstI minor allele (S2) in CRF-HTG was 0.44, which was significantly higher than that in CRF-NTG (0.17). Frequencies of MspI minor allele (M2) in CRF-HTG and CRF-NTG were not significantly different (0.5 vs 0.32) (p=0.07). Frequencies of S2-M2 genotype were 0.65 in CRF-HTG, and 0.27 in CRF-NTG (p>0.005). These data indicate that genetic variation of the apo AI-CIII-AIV gene cluster may serve as one of the causes of HTG in CRF.

Efecto de las lipoproteínas ricas en triglicéridos sobre la relación entre C-LDL y Apo B determinada por EID en suero total: I. indicadores de riesgo para la enfermedad coronaria. Valores de Apo B/C-HDL / Effect the triglyceride rich lipoproteins upon the relation between C-LDL and Apo B determined by EID in total serum: I.rick indications of coronary disease. Values of Apo B/C-HDL

En este trabajo se determinaron los valores promedio, desviación estándar y percentilos para el cociente Apo B/C-HDL y, por otra parte, se analizó el efecto de las lipoproteínas ricas en triglicéridos sobre la relación entre C-LDL y Apo B, determinada por electroinmunodifusión en suero total. Se estudiaron 74 individuos de 20 y más años, aparentemente sanos. Para Apo B/C-HDL se obtuvo un valor medio de 2,16+0,78. El percentilo 50 fue 2,00, el percentilo 75 fue 2,60 y el percentilo 95 fue 3,60. Los individuos con Apo B/C-HDL>3,60 estarían en riesgo respecto de la aterosclerosis coronaria. La relación entre C-LDL y Apo B, es importante para la detección de sujetos con hiperapo B, la cual está fuertemente relacionada con la aterosclerosis coronaria. Utilizando los triglicéridos como estimadores de masa de las lipoproteínas ricas en triglicéridos, se halló que mientras TG<160 mg/dl la correlación entre Apo B y C-LDL fue r= +0,65,P <0,001. Un 86% de los pacientes con C-LDL entre 80 y 165 mg/dl tenían Apo B entre 55 y 120 mg/dl, mientras que un 12% tenían Apo B por encima de 120 mg/dl. En estos pacientes se puede suponer la presencia de hiperapo B en estas condiciones experimentales. Cuando TG>160 mg/dl, la correlación entre Apo B y C-LDL disminuye a r=+0,39,P<0,1. Un 21% de los pacientes con C-LDL entre 80 y 165 mg/dl tenían Apo B entre 55 y 120 mg/dl, pero un 79% tenían Apo B por encima de 120 mg/dl. En estas condiciones experimentales no se podrían discriminar los pacientes con hiperapo B.

Inhibition of lipoprotein lipase activity by high density lipoprotein & apolipoproteins C, E & A in rhesus monkeys.

Experiments were conducted to study the effects of high density lipoprotein (HDL) and apolipoproteins C, E, and A on lipoprotein lipase activity in rhesus monkeys. The lipoprotein lipase activity was inhibited up to 32 +/- 6 per cent by monkey HDL. This inhibition was considerably decreased (2 +/- 0.02%) by using apolipoprotein-poor HDL. Apolipoproteins C and E inhibited the hydrolysis of activated intralipid by monkey lipoprotein lipase to a maximum of 83 +/- 7 and 57 +/- 5 per cent respectively. Apolipoprotein A produced little inhibition of lipoprotein lipase activity. The results of these studies demonstrate that HDL and apolipoproteins compete with the substrate for the binding to lipoprotein lipase in rhesus monkeys.