Multicentric evaluation of the homogeneous LDL-cholesterol Plus assay: comparison with beta-quantification and Friedewald formula

ObjectivesTo evaluate the analytical and clinical performance of a new version of the LDL-C Plus assay and compare it with the beta-quantification (BQ) method in a multicenter study.Design and methodsDirect LDL-C was measured in 169 fresh pooled samples and in 830 clinical samples with known LDL-C by BQ. The reactivity of lipoproteins and the effect of hemoglobin, bilirubin and chylomicrons (CM) were studied.ResultsDirect LDL-C total imprecision was < 2.2%; inaccuracy < ± 2.5% (unaffected by triglycerides up to 9.5 mmol/L); and total error 9.8%. Direct assay reacted with 95%, 50% and 25% of the cholesterol in the LDL, intermediate (IDL) and VLDL fractions, respectively. A significant association was observed with BQ. Icteric samples showed a negative bias and the effect of CM was variable. A positive bias was observed when VLDL-cholesterol/triglyceride ratio was > 0.57.ConclusionsLDL-C Plus assay represents a valid alternative to BQ for clinical laboratories.     

Increased large VLDL and small LDL particles are related to lower bilirubin in Type 2 diabetes mellitus

ObjectivesBilirubin may protect against atherosclerotic cardiovascular disease by virtue of its anti-oxidative properties, but lower bilirubin may also be associated to atherogenic lipoprotein abnormalities. We determined associations of plasma (apo)lipoproteins and lipoprotein subfractions in subjects with and without type 2 diabetes mellitus (T2DM).Design and methodsPlasma (apo)lipoproteins, lipoprotein subfractions (nuclear magnetic resonance spectroscopy) and serum total bilirubin levels were determined in 53 T2DM patients and in 53 non-diabetic subjects.ResultsTriglycerides, large VLDL, small LDL and small HDL particles were increased (all p < 0.05), whereas HDL cholesterol, apoA-I and large HDL particles were decreased (all p < 0.05), coinciding lower bilirubin levels in T2DM (p < 0.001). In age- and sex-adjusted analysis, total cholesterol, non-HDL cholesterol, triglycerides, apoB, apoE, large VLDL and small LDL were negatively correlated with bilirubin, but HDL cholesterol was positively correlated with bilirubin in T2DM (p < 0.05 to p < 0.001). Multivariable linear regression analyses demonstrated that in all subjects combined total cholesterol, non-HDL cholesterol, triglycerides and apoE were negatively associated with bilirubin after adjustment for age, sex, T2DM, body mass index and alanine aminotransferase (all p < 0.05). Further multivariable linear regression analysis showed that large VLDL and small LDL particles were negatively associated with bilirubin, whereas large HDL particles were associated positively with bilirubin (p < 0.05).ConclusionsIncreased triglycerides, as well as large VLDL and small LDL particles are associated negatively, whereas HDL cholesterol is associated positively with bilirubin in T2DM. The proposed pro-atherogenic effects of low bilirubin could in part be attributed to relationships with abnormalities in (apo)lipoproteins and lipoprotein subfraction characteristics.     

Does non-alcoholic fatty liver impair alterations of plasma lipoproteins and associated factors in metabolic syndrome?

BackgroundHepatic steatosis (HS) is closely associated to metabolic syndrome (MS). Both, VLDL-triglyceride oversecretion and intrahepatic deposits, can take place. We evaluated VLDL characteristics, CETP, hepatic lipase (HL), IDL and small dense LDL (sdLDL), in patients with HS associated to MS.MethodsWe studied 3 groups matched by age and sex: 25 MS patients with HS (diagnosed by ultrasonography), 25 MS patients without HS and 25 healthy controls. Main measurements were: lipid profile, free fatty acids, VLDL composition, VLDL size by HPLC, CETP and HL activities, IDL-cholesterol and sdLDL-cholesterol.ResultsPatients with HS presented higher triglyceride levels, HOMA-IR and free fatty acids, VLDL mass and VLDL-apoB (p < 0.05). No differences in VLDL composition were observed. MS groups presented higher proportion of large VLDL than controls (p < 0.05). HS group showed higher CETP than controls (p = 0.01) and almost higher than MS without HS (p = 0.06). CETP correlated with VLDL-cholesterol content, r = 0.48, p < 0.005. The increase in sdLDL-cholesterol correlated with CETP (r = 0.47) and HL (r = 0.56), independent of insulin resistance (p < 0.003).ConclusionDespite intrahepatic fat, patients with HS secreted higher number of VLDL particles. CETP would have a remodeling action on VLDL in circulation, enriching it in cholesterol and also favoring, together with HL, the formation of sdLDL.     

Plasma proprotein convertase subtilisin–kexin type 9 is predominantly related to intermediate density lipoproteins

ObjectivesProprotein convertase subtilisin–kexin type 9 (PCSK9) is a key regulator of low density lipoprotein (LDL) receptor processing, but the PCSK9 pathway may also be implicated in the metabolism of triglyceride-rich lipoproteins. Here we determined the relationship of plasma PCSK9 with very low density lipoprotein (VLDL) and LDL subfractions.Design and methodsThe relationship of plasma PCSK9 (sandwich enzyme-linked immunosorbent assay) with 3 very low density lipoprotein (VLDL) and 3 low density lipoprotein (LDL) subfractions (nuclear magnetic resonance spectroscopy) was determined in 52 subjects (30 women).ResultsIn age- and sex-adjusted analysis plasma PCSK9 was correlated positively with total cholesterol, non-high density lipoprotein cholesterol and LDL cholesterol (r = 0.516 to 0.547, all p < 0.001), as well as with triglycerides (r = 0.286, p = 0.044). PCSK9 was correlated with the VLDL particle concentration (r = 0.336, p = 0.017) and with the LDL particle concentration (r = 0.362, p = 0.010), but only the relationship with the LDL particle concentration remained significant in multivariable linear regression analysis. In an analysis which included the 3 LDL subfractions, PCSK9 was independently related to intermediate density lipoproteins (IDL) (p < 0.001), but not to other LDL subfractions.ConclusionsThis study suggests that plasma PCSK9 predominantly relates to IDL, a triglyceride-rich LDL subfraction. The PCSK9 pathway may affect plasma triglycerides via effects on the metabolism of triglyceride-rich LDL particles.     

An innovative method for determining lipemia interference in blood specimens

BackgroundLipemia interference in blood samples is usually determined by adding exogenous substances that cause turbidity or by using ultracentrifugation to clarify the sample. However, there are a number of problems associated with these methods, which make it difficult to ascertain with certainty that lipemia is the cause of interference. We assessed a novel method for evaluating lipemia interference.MethodsLipemic and non-lipemic serum samples, with similar HDL cholesterol concentrations, were mixed in various proportions (5 concentrations) and assayed for HDL and triglycerides. Thus, matched HDL samples with increasing triglycerides concentrations were tested. We then calculated the percent recovery for HDL for each mixture.ResultsSix matched sets of samples had HDL recoveries ranging from 95.9% to 101.1% (n = 6 sets, 5 concentrations per set, total of 30 concentrations), with HDL concentrations ranging from 0.78 to 2.16 mmol/l. Triglycerides concentrations in these samples ranged from 1.06 to 9.78 mmol/l for the 30 concentrations.ConclusionsWe determined that there was no triglycerides interference on the HDL method performed on the Hitachi S40 Clinical Analyzer up to a triglycerides concentration of 9.78 mmol/l. This matching method is simple to perform and proved useful in evaluating interference due to lipemia.     

Profiles of inflammatory markers and lipoprotein subclasses in patients undergoing continuous ambulatory peritoneal dialysis

BackgroundPatients undergoing continuous ambulatory peritoneal dialysis (CAPD) often have inflammation and dyslipidemia that accelerate to atherosclerosis. This study aimed to evaluate chronic inflammation and dyslipidemia in CAPD patients.MethodsWe measured inflammatory markers and lipoprotein subclasses in 20 CAPD patients (12 men and 8 women, aged 59.5 ± 9.9 y) and 20 gender-matched controls. Lipoproteins were separated by high-performance liquid chromatography (HPLC) using an anion-exchange column.ResultsHigh-sensitivity C-reactive protein and serum amyloid A protein (SAA) were higher among CAPD patients vs. controls (1.6 ± 2.2 vs. 0.8 ± 1.2 mg/l, p < 0.05; 11.9 ± 12.8 vs. 4.5 ± 2.4 mg/l). HPLC analysis revealed that chylomicron, VLDL, and IDL cholesterol levels were higher among CAPD vs. controls. In contrast, HDL cholesterol was lower among CAPD patients vs. controls. In the subgroup analysis, SAA levels were significantly lower among patients receiving CAPD for > 3 y than among controls. However, IDL cholesterol was consistently higher among CAPD patients vs. controls.ConclusionsCAPD patients have chronic inflammation and dyslipidemia. IDL cholesterol is the only lipoprotein subclass that is consistently elevated regardless of CAPD duration. More attention should be paid to dyslipidemia in the management of the CAPD patients.     

Performance evaluation of Siemens ADVIA Centaur enhanced estradiol assay and a split sample comparison with liquid chromatography-tandem mass spectrometry

ObjectivesThe objective of this study was to evaluate the newly developed Siemens ADVIA Centaur® enhanced Estradiol (eE2) assay and compare it with a well-established estradiol liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.Design and methodsThe Siemens eE2 assay was evaluated using the Clinical and Laboratory Standards Institute evaluation protocols. Split patient samples were compared with the eE2 assay, the current ADVIA Centaur E2-6 Ill assay; and LC-MS/MS method by API5000 mass spectrometer.ResultsWithin-run and total imprecision of the eE2 assay demonstrated coefficient of variations of 5.7%, 3.2%, 1.5%, and 10.4%, 7.3%, and 6.8%, at levels of 380, 752, and 2051 pmol/L, respectively. The method comparisons showed: eE2 = 0.903(E2-6 III) –16.2, R² = 0.938, average bias = ? 12.3%; and eE2 = 0.946(LC-MS/MS) + 19.5, R² = 0.925, average bias: 0%.ConclusionThe Siemens eE2 assay correlates well with LC-MS/MS. This method is reliable, and appropriate for routine clinical laboratory use.     

Impact of bezafibrate and atorvastatin on lipoprotein subclass in patients with type III hyperlipoproteinemia: result from a crossover study

BackgroundWe elucidated the difference between the effects of bezafibrate and atorvastatin in hypertriglyceridemia with apoE2/2 and 3/3.MethodsAn open randomized crossover study consisted of a 4-week treatment period with bezafibrate (400 mg daily) or atorvastatin (10 mg daily) and a 4-week wash-out period.ResultsBezafibrate significantly decreased serum concentrations of triglyceride (apoE2/2, E3/3: ?49.2%, ?39.0%) and significantly increased high-density lipoprotein (HDL) cholesterol (+ 28.5%, + 26.1%) in both apoE phenotypes but did not change serum concentrations of low-density lipoprotein (LDL) cholesterol. Atorvastatin significantly decreased serum concentrations of LDL cholesterol (? 34.0%, ?30.0%) and triglyceride (? 27.6%, ?25.8%) in both apoE phenotypes but did not change HDL cholesterol concentrations. Changes in cholesterol in lipoprotein subfractions were not different between apoE2/2 and E3/3. Bezafibrate changed cholesterol distribution from small- to large-sized LDL and from large- to small-sized HDL. On the other hand, atorvastatin decreased cholesterol in all apoB-containing lipoprotein subfractions but did not change any of the HDL subfractions.ConclusionBezafibrate and atorvastatin improve atherogenic dyslipidemia in considerably different ways. Extrapolating from the present data, we presume that the combination of these drugs may contribute to reduce LDL-C/HDL-C ratio effectively as well as lowering concentrations of serum triglyceride.     

Assessment of paraoxonase activity and lipid peroxidation levels in diabetic and senile subjects suffering from cataract

Objectives:The purpose of this study was to evaluate antioxidant effect of paraoxonase 1 activity and malondialdehyde (MDA) levels as a marker of oxidative stress in patients suffering from cataract due to diabetes and aging.Design and methods:One hundred cataract patients (senile and diabetic) and age- and sex-matched controls were studied. Paraoxonase 1 and arylesterase activities in plasma samples were measured using paraoxon and phenylacetate as substrates, respectively. The magnitude of lipid peroxidation was established by measuring plasma MDA and oxidized low-density lipoprotein (ox LDL) levels. One-way ANOVA was employed for analysis of results.Results:We observed significantly lower plasma paraoxonase and arylesterase activities in senile and diabetic cataractous patients as compared to respective controls (p < 0.001). Plasma MDA and ox LDL levels were found to be higher in patients suffering from cataract (p < 0.001).Conclusions:The results of present study suggest that the observed decrease in PON1 activity may be due to increase in oxidative stress. It can be concluded that lower paraoxonase activity could contribute to the higher risk of cataract formation.     

Measurement of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 after delayed separation of whole blood samples

Objectives:Epidemiological studies benefit from unbiased blood specimens collected with minimal cost and effort of blood collection and storage. We evaluated the stability of IGF-1 and IGFBP-3 in whole blood samples stored at room temperature to justify delays in blood processing.Design and methods:Total IGF-1 and IGFBP-3 levels were measured in EDTA plasma (n = 12), heparin plasma (n = 12) and serum (n = 10) samples of healthy volunteers after blood processing delays up till 14 days. Stability of measured IGF-1 and IGFBP-3 levels was tested by paired t-test and a linear mixed effect model.Results:Longitudinal analysis showed that IGF-1 levels were not significantly affected by blood processing delays in EDTA tubes (p = 0.18) and IGFBP-3 levels were marginally stable (p = 0.06). In heparin plasma and serum, however, IGF-1 increased over time of delayed processing and IGFBP-3 levels tended to decrease (p < 0.01).Conclusion:Total IGF-1 and IGFBP-3 levels are stable in whole blood collected in EDTA tubes at room temperature up till 7 days, allowing a delay in blood processing to reduce costs in large multi-center studies.     

Carotid intima media thickness is related positively to plasma pre ß-high density lipoproteins in non-diabetic subjects

BackgroundLipid-poor or lipid-free high density lipoprotein (HDL) particles, designated pre ß-HDL, stimulate removal of cell-derived cholesterol to the extracellular compartment, which is an initial step in the reverse cholesterol transport pathway. Pre ß-HDL levels may be elevated in subjects with established cardiovascular disease. We determined the relationship of carotid intima media thickness (IMT), a marker of subclinical atherosclerosis, with pre ß-HDL in subjects without clinically manifest cardiovascular disease.MethodsIMT and plasma pre ß-HDL, assayed by crossed immuno-electrophoresis, were determined in 70 non-diabetic subjects (aged 56 ± 9 years; non-smokers only; 27 women).ResultsIMT was correlated positively with pre ß-HDL, both expressed as plasma apolipoprotein (apo) A-I concentration (r = 0.271, p = 0.023) and as% of apo A-I (r = 0.341, p = 0.004). In contrast, IMT was correlated inversely with HDL cholesterol (r = ? 0.253, p = 0.035). IMT was also related positively to pre ß-HDL after adjustment for age, sex, systolic blood pressure (in apoA-I concentration, ß = 0.203, p = 0.043; in% of plasma apoA-I, ß = 0.235, p = 0.023). IMT remained associated with pre ß-HDL after additional adjustment for either body mass index, plasma glucose, cholesterol, triglycerides, HDL cholesterol, apoA-I and apoB.ConclusionSubclinical atherosclerosis may relate to higher plasma pre ß-HDL independently of apoA-I and HDL cholesterol levels.     

Evaluation of a gel-permeation high-performance liquid chromatography for determining triglyceride levels in serum major lipoproteins, compared with the ultracentrifugation/precipitation method

ObjectivesTo evaluate the gel permeation high-performance liquid chromatography (GP-HPLC) method for determination of triglyceride (TG) levels in low-density lipoprotein (LDL) and high-density lipoprotein (HDL).Design and methodsThe GP-HPLC and the ultracentrifugation(UC)/precipitation methods were used and compared.ResultsThere was no significant difference in measured levels of LDL-triglyceride between the two methods, but the HDL-triglyceride levels measured by the GP-HPLC technique were significantly higher than the UC/precipitation one (145 ± 47 mg/L and 121 ± 45 mg/L respectively, n = 38, p < 0.0001).ConclusionsA GP-HPLC technique provides LDL-TG levels comparable to those obtained by the UC/precipitation method.     

Mutations in APOA-I and ABCA1 in Norwegians with low levels of HDL cholesterol

BackgroundEpidemiological studies have shown that low levels of plasma high density lipoprotein (HDL) cholesterol are associated with increased risk of ischemic heart disease (IHD), but it appears that genetic forms of low HDL cholesterol levels, as opposed to lifestyle-induced low levels of HDL cholesterol, do not result in increased risk of IHD. Therefore, the etiology of reduced levels of plasma HDL cholesterol may represent a factor that should be considered in risk stratification with respect to primary prevention. Genes encoding proteins involved in HDL metabolism, such as the ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein (apo) A-I genes, are candidate genes for harboring mutations that lead to low HDL cholesterol levels.MethodsThe ABCA1 and apoA-I genes in 56 Norwegian patients, with a mean HDL cholesterol level of 0.53 (± 0.15) mmol/l, were subjected to DNA sequencing.ResultsSeveral mutations were identified in the ABCA1 gene, and two mutations were identified in the apoA-I gene. A total of 18 patients (32%) were carriers of mutations considered to be pathogenic. Their mean HDL cholesterol level was 0.45 (± 0.15) mmol/l compared to 0.57 (± 0.14) mmol/l in noncarriers (p < 0.005).ConclusionMutations in the genes encoding ABCA1 and apoA-I are common in Norwegians, with a markedly decreased HDL cholesterol level.     

High density lipoprotein-anionic peptide factor effect on reverse cholesterol transport in type 2 diabetic patients with and without coronary artery disease

ObjectivesTo verify if HDL3 Anionic Peptide Factor (HDL3-APF) is as an apolipoprotein that promotes the reverse cholesterol transport.Design and methodsWe investigated a possible association between plasma HDL3-APF concentration, cholesterol efflux from Fu5AH cells and cholesteryl ester transfer protein (CETP) activity in type 2 diabetic patients with coronary artery disease (CAD) (n = 36), those without CAD (n = 20), and 37 healthy subjects.ResultsPlasma APF concentrations were decreased in diabetics with CAD compared to controls (p < 0.01). Cellular cholesterol efflux was decreased in diabetics without and with CAD, (p < 0.01 and p < 0.001 respectively). CETP activity was significantly elevated in all patient groups. Multiple linear regression analysis shows that cholesterol efflux was independently and positively related only to APF concentrations in controls.ConclusionsAPF is likely to be a key independent factor for promoting cellular cholesterol efflux in healthy subjects. However this association is altered in type 2 diabetes.     

Pro-inflammatory and atherogenic circulating factors in non-alcoholic fatty liver disease associated to metabolic syndrome

BackgroundIt is not elucidated if liver fat deposits associated to metabolic syndrome (MS) aggravate the atherogenic state. We evaluated, in MS patients, if the presence of non-alcoholic hepatic steatosis (HS) determines differences in inflammatory markers and VLDL characteristics.MethodsSeventy-five patients with MS were divided into 2 groups depending on the presence or absence of HS, assessed by ultrasound. Lipid profile, free fatty acids (FFA), VLDL composition, adiponectin, tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), and soluble adhesion molecules (sVCAM-1 and sICAM-1) were measured.ResultsHS patients presented increased triglycerides levels, HOMA-IR and FFA. Patients with HS showed a reduction in adiponectin (p = 0.04) and increase in hs-CRP (p = 0.02), independently of insulin-resistance (IR). FFA correlated positively with TNF-α (p = 0.04) and inversely with adiponectin (p = 0.01). hs-CRP correlated with all inflammatory markers, independently of IR: TNF-α (r = 0.34, p = 0.02), sVCAM-1 (r = 0.29 p = 0.03), sICAM-1 (r = 0.56, p = 0.01), adiponectin (r = ?0.34, p = 0.04). HS patients presented higher VLDL mass and number of particles. Adiponectin correlated with VLDL cholesterol content (r = ?0.47, p = 0.04), independently of IR. VLDL, once secreted, would suffer from changes, becoming more atherogenic.ConclusionsSimple HS would play an important role increasing cardiovascular risk, independently of IR. hs-CRP may represent a useful biomarker of this condition.     

Plasma ascorbic acid preparation and storage for epidemiological studies using TCA precipitation

Objectives:To introduce a procedure to validate an ascorbic acid method using trichloroacetic acid (TCA) for plasma stabilization at different storage temperatures.Methods:EDTA and heparin plasma were precipitated with TCA (1:5) containing 0.54 mol/L EDTA, or without. Samples were stored at ? 20 °C and ? 70 °C and their stability was tested at room temperature for 24 h.Results:A significant 40% loss (p < 0.001) of plasma ascorbic acid was found when EDTA samples with added EDTA were stored at ? 20 °C for 2–4 weeks compared with storage at ? 70 °C. Ascorbic acid in heparin plasma without added EDTA was most unstable and samples left at room temperature for 24 h lead to almost a total loss of ascorbic acid. Addition of EDTA to the TCA solution improved stability of samples of both plasma types at room temperature.Conclusion:The recommended procedure for ascorbic acid determination in plasma stabilized with TCA is immediate storage at ? 70 °C and inclusion of EDTA into the TCA solution.     

Butyrylcholinesterase activity is reduced in haemodialysis patients: Is there association with hyperhomocysteinemia and/or oxidative stress?

Objectives:To quantify serum butyrylcholinesterase activity in haemodialysis patients and to evaluate if the homocysteine levels and/or oxidative stress biomarkers have an effect on butyrylcholinesterase.Materials and methods:Blood samples were collected from patients and healthy subjects (control). The plasma homocysteine and TBARS levels; serum butyrylcholinesterase activity; blood δ aminolevulinic acid dehydratase (ALA-D) activity and methahaemoglobin were analyzed. The mortality of the patients was also evaluated after 3 years.Results:The homocysteine was increased and butyrylcholinesterase decreased compared to control (p < 0.05). TBARS and methahaemoglobin were increased and ALA-D decreased (p < 0.05). The following correlations were found: homocysteine with butyrylcholinesterase (? 0.44); methahaemoglobin (0.41); ALA-D (? 0.68); and TBARS (0.66). The partial correlation between homocysteine with butyrylcholinesterase, withdrawn the effect of TBARS, was ? 0.30; all p < 0.05. Moreover, it was observed that 22% of the patients died due to cardiovascular problems.Conclusion:Thus, our findings support a direct association between the reduction of butyrylcholinesterase by the increase of homocysteine and an indirect effect by increase in oxidative stress.     

Predominance of large VLDL particles in metabolic syndrome, detected by size exclusion liquid chromatography

ObjectiveTo study size heterogeneity of triglyceride rich lipoproteins (TRL) in metabolic syndrome (MS).Design and methodsThirty MS patients and 14 healthy subjects were included. In fasting serum we measured: lipid profile, free fatty acids (FFA) and adiponectin; TRL were isolated (d < 1.006 g/mL) and analysis by size exclusion HPLC followed by UV detection was performed; each subfraction was expressed as percentage of total TRL.ResultsMS patients, even those with normal triglycerides, presented higher proportion of very large VLDL (90 nm diameter) and large VLDL (60 nm) and slightly lower of typical VLDL (37 nm) (p < 0.04); increased FFA (p = 0.04) and lower adiponectin (p = 0.001). FFA correlated with large VLDL% (r = 0.58; p = 0.003), independently of insulin-resistance and waist. Furthermore, the lower the adiponectin, the greater the predominance of large VLDL (r = ? 0.40; p = 0.04).ConclusionMS was associated with large VLDL, described as more atherogenic beyond triglyceride levels. Size exclusion HPLC would represent a useful tool for assessing subfractions' lipoprotein profile.     

A promoter polymorphism − 2122C>T of CHI3L1 is associated with serum low density lipoprotein cholesterol level in Korean subjects

ObjectivesThis study assessed the effects of 10 tagging single nucleotide polymorphisms (SNPs) of the CHI3L1 gene on serum LDL cholesterol levels in 290 Korean subjects.Design and methodsGenotyping analyses of SNPs were conducted by TaqMan® method. The effects of the promoter SNP on mRNA expression and nuclear factor binding were measured by real-time PCR and electrophoretic mobility shift assay, respectively.ResultsAmong 10 tagging SNPs, ? 2122C>T SNP (rs946261) in the promoter region was significantly associated with serum LDL cholesterol level (P = 0.005). The T allele of ? 2122C>T was associated with significantly increased mRNA expressions in peripheral blood cells of the subjects, and also increased a nuclear factor binding measured by an electrophoretic mobility shift assay.Conclusions? 2122C>T of CHI3L1, a promoter SNP which affects the mRNA expression and nuclear factor binding, is significantly associated with serum LDL cholesterol levels in Korean subjects.     

Lovastatin enhances paraoxonase enzyme activity and quells low-density lipoprotein susceptibility to oxidation in type 2 diabetic nephropathy

Objectives:To investigate the effect of lovastatin therapy and withdrawal on paraoxonase 1 (PON1) and arylesterase (ARE) activities, and low-density lipoprotein cholesterol (LDL-C) susceptibility to oxidation in people with type 2 diabetic nephropathy (T2DN).Design and methods:Lovastatin (20 mg/day) was administered to 30 people with T2DN for 90 days and then withdrawn for 30 days. PON1 and ARE activities were measured by the spectrophotometric method. Susceptibility of LDL-C to oxidation was determined as the production of conjugated dienes.Results:After 90 days of lovastatin intervention, PON1 and ARE activities and LDL-C lag phase were significantly increased (p = 0.004, 0.002, and < 0.001), while after 30 days of lovastatin withdrawal, PON1 and ARE activities and LDL-C lag phase had not changed significantly.Conclusion:Lovastatin therapy improves PON1 and ARE activities, and LDL-C susceptibility to oxidation. Despite withdrawal of lovastatin, PON1 and ARE activities, and LDL-C susceptibility to oxidation remain unchanged in people with T2DN.