Combined Hyperlipidemia Research Articles

Effects of Armolipid Plus on small dense LDL particles in a sample of patients affected by familial combined hyperlipidemia.

The aim of this study was to test small dense LDL changes with Armolipid Plus treatment in patients with familial combined hyperlipidemia (FCHL). After 4 weeks, 30 patients with FCHL were included in an 8-week, randomized, double-blind study and were taking, in addition to the standard diet, either placebo or Armolipid Plus. The placebo group showed no statistically significant differences in the studied parameters; instead, in the Armolipid Plus group, statistically significant reduction differences were detected in BMI (p = 0.010), LDL score (p = 0.035) and an increase in mean LDL particle diameter (p = 0.040). The combination of a standard diet with Armolipid Plus is able to reduce LDL score and increase LDL particle diameter in a group of FCHL after 8 weeks of treatment.

Single and mixed dyslipidaemia in Canadian primary care settings: findings from the Canadian primary care sentinel surveillance network database

ObjectivesDyslipidaemia is a major risk factor to cardiovascular disease (CVD)—the leading cause of death worldwide. Limited data are available about the prevalence of various dyslipidaemia in Canada. The objective of...

EFFICACY AND SAFETY OF THE PCSK9 INHIBITOR EVOLOCUMAB IN PATIENTS WITH MIXED HYPERLIPIDEMIA

EFFICACY AND SAFETY OF THE PCSK9 INHIBITOR EVOLOCUMAB IN PATIENTS WITH MIXED HYPERLIPIDEMIA

DETERMINANTS OF SMOKING CESSATION IN YOUNG WOMEN AND MEN AFTER ACUTE CORONARY SYNDROME

s S295 For this mixed hyperlipidemia subset efficacy was evaluated in four phase 3 randomized studies (n1⁄41148) and safety, from the phase 2 and phase 3 studies (n1⁄42092) and their open label extension studies (n1⁄41485). Efficacy analyses were based on 12-week studies, while safety analyses included data from all available studies. Treatment differences were calculated vs. placebo and ezetimibe by evolocumab dose. RESULTS: Patients with mixed hyperlipidemia taking evolocumab had mean SD baseline LDL-C of 3.4 1.4 mmol/L, median (Q1, Q3) triglycerides of 2.0 (1.6, 2.5) mmol/L and mean SD HDL-C of 1.2 0.3 mmol/L. The mean treatment difference in percent change from baseline in LDL-C (mean of weeks 10 and 12) with evolocumab was approximately -67% vs. placebo and -42% vs. ezetimibe (all p<0.001) (figure) compared to -65% vs. placebo and -40% vs. ezetimibe in the entire study population. Treatment differences for evolocumab vs. placebo and ezetimibe followed a similar pattern for non-HDL-C, apolipoprotein B, and lipoprotein(a) (figure). Evolocumab was well tolerated, with balanced rates of serious adverse events or adverse events leading to discontinuation of the investigational product for evolocumab vs. placebo and ezetimibe (table). CONCLUSION: This analysis studied the effect of evolocumab in patients with mixed hyperlipidemia. LDL-C reduction with evolocumab in patients with mixed hyperlipidemia was similar to the LDL-C reduction seen in previous reports of the entire study population. Amgen Inc. 555 DETERMINANTS OF SMOKING CESSATION IN YOUNG WOMEN AND MEN AFTER ACUTE CORONARY SYNDROME

Essential phospholipids as a supportive adjunct in the management of patients with NAFLD

Background and study aimsTreatment of nonalcoholic fatty liver (NAFLD) is important because NAFLD patients have a 1.7-fold increase in standardised age and gender matched mortality. Currently treatment is based on life style modification and managing comorbid associating disease. Other medications remain experimental. Essential phospholipid (EPL) is a nutrient for the liver, helping to maintain vitality of cell membranes where the vast majority of liver activities are regulated.We performed a randomised open label study to evaluate EPL as an adjuvant nutrient to the treatment of primary NAFLD or NAFLD with comorbid disease. Patients and methodThree groups of NAFLD patients were recruited: lone (n=113), diabetes mellitus type 2 (n=107) and mixed hyperlipidaemia (n=104). Diagnosis was established by excluding other chronic liver diseases. A standard diet and physical activity plan were advised to all patients. 1800mg of EPL a day was given for 24weeks, followed by 900mg for 48weeks. ResultsEssential phospholipid EPL led to a significant improvement of symptoms and a mean reduction of ALT of 50.8IU and AST of 46.1IU per patient (p<0.01). Abdominal ultrasonography indicated normalisation in 4.6% and a shift from grade II to grade I in 24% of patients. Liver stiffness measurement indicated an improvement in 21.1%, with a mean reduction in the LSM of 3.1K Pascal/patient. Reducing the dosage after six months led to a limited relapse in 43.8–63.2% of patients, for lone and NAFLD with co-morbid conditions. ConclusionEssential phospholipid (EPL) as a nutritional supplement resulted in a significant improvement in clinical parameters and transaminases for all NAFLD patients. Ultrasound and LSM revealed modest improvement. There is a need for uninterrupted maintenance to avoid relapse.

Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups

An improved understanding of non-alcoholic fatty liver disease epidemiology would lead to identification of individuals at high risk of developing chronic liver disease and extra-hepatic complications, thus contributing to more effective case finding of non-alcoholic fatty liver disease among selected groups.We aimed to illustrate the epidemiology of non-alcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published until May 2015 using relevant and pertinent keywords “nonalcoholic fatty liver disease” and “diabetes”, “obesity”, “hyperlipidaemia”, “familial heterozygous hypobetalipoproteinaemia”, “hypertension”, “metabolic syndrome”, “ethnicity”, “family history” or “genetic polymorphisms”.We found that age, sex and ethnicity are major physiological modifiers of the risk of non-alcoholic fatty liver disease, along with belonging to “non-alcoholic fatty liver disease families” and carrying risk alleles for selected genetic polymorphisms. Metabolic syndrome, diabetes, obesity, mixed hyperlipidaemia and hypocholesterolaemia due to familial hypobetalipoproteinaemia are the major metabolic modifiers of non-alcoholic fatty liver disease risk. Compared with these metabolic conditions, however, arterial hypertension appears to carry a relatively more modest risk of non-alcoholic fatty liver disease.A better understanding of the epidemiology of non-alcoholic fatty liver disease may result in a more liberal policy of case finding among high-risk groups.

Familial hyperlipidaemia

This article provides an overview of the different types of familial hyperlipidaemia that may be encountered in clinical practice, namely, familial combined hyperlipidaemia (FCH) and familial hypercholesterolaemia (FH). Owing to their complexity, apolipoprotein disorders will not be covered. The underlying causes and clinical consequences of FCH and FH will be discussed, in addition to management strategies that can be implemented to mitigate against such consequences of familial hyperlipidaemia.

Dysbetalipoproteinemia: an extreme disorder of remnant metabolism.

Lipoprotein metabolism and the role of apolipoprotein E in the pathogenesis of dysbetalipoproteinemia. Remnant lipoproteins, modulated by lifestyle and genetic factors, are atherogenic. Dysbetalipoproteinemia could be viewed as a monogenic disorder of remnant metabolism. Elevated plasma triglyceride and cholesterol concentrations (mixed hyperlipidemias) are commonly encountered and dysbetaliproteinemia should be considered in this setting. Dysbetalipoproteinemia (remnant clearance disease, Fredrickson type III hyperlipidemia) is an uncommon dyslipoproteinemia related to mutations in apolipoprotein E that disrupt the clearance of remnants of triglyceride-rich lipoproteins; it may be overlooked because xanthomata of the skin and/or tendons occur in a minority of patients. The diagnosis ideally requires the demonstration of remnant lipoprotein accumulation and a genetic cause. Genotyping for apolipoprotein E2 may not prove the diagnosis as it may be associated with low plasma lipid values. The recent association of remnant lipoproteins with atherosclerosis along with many factors that modulate remnant lipoprotein metabolism underscores the importance of recognising dysbetalipoproteinemia as an extreme state of remnant lipoprotein accumulation. Although there may be some differences between remnants in the general population and dysbetalipoproteinemia, it is clear that remnants promote atherosclerosis. Current treatment strategies are adequate but new strategies could also be of benefit in dysbetalipoproteinemia.

Complementary effect of combination of statins with coenzyme q10 and omega-3 fatty acids in patients with combined dyslipidemia

s / Atherosclerosis 241 (2015) e149ee229 e207 EAS-0936. COMPLEMENTARY EFFECT OF COMBINATION OF STATINS WITH COENZYME Q10 AND OMEGA-3 FATTY ACIDS IN PATIENTS WITH COMBINED DYSLIPIDEMIA S. T oth, M. Sajty, T. Pek arov a, J. Feda cko, K. Spi s akov a, D. Pella. 1st Department of Internal Medicine, avol Jozef Saf arik University in Ko sice Faculty of Medicine, Kosice, Slovakia * Corresponding author. Introduction: Several studies have described a positive effect of statins and omega-3 PUFA or CoQ10 on cardiovascular system. The aim of this study was to determine the effect of this triple combination on various parameters associated with the progression of cardiovascular disorders. Material and methods: 90 patients taking statins at a dose, which allowed target LDL levels, but with remained elevated TG levels (1.5-4.5 mmol/L) were randomized into three groups (each N1⁄430). In the placebocontrol group we indicated continued administration of statins. In the groups with additive treatment patients continued use of statins in combination with omega-3 PUFA 3 g/day respectively omega-3 PUFA 3 g/ day and 200 mg CoQ10/day during three months. After 3 months (± 1 week), we performed a final examination and collection of samples. We observed the lipid profile (total cholesterol, HDL, LDL, TG), hsCRP levels, activity SOD and GPx and presence of negative pleiotropic effects of statins. Results: Combination of statins with omega-3 PUFA significantly reduced TG and increased HDL levels. Significant reduction of hsCRP and increse of GTx and SOD was detected as well. Triple combination significantly decreased LDL and increased HDL in compare to control and dual combination. hsCRP significantly decreased in compare to control and dual combination group. SOD significantly increased in compare to control and dual combination group and GPx in compare to control. Conclusion: According to our study we suggest positive and complementary effect of combined therapy on lipid parameters, endothelial function and some negative pleiotropic effects of statins. EAS-0948. STATINS IMPACT IN A PORTUGUESE PRIMARY CARE UNIT J. Frutuoso. Internal Medicine, Hospital Jos e Joaquim Fernandes, Beja,

Targeting HSP90 Ameliorates Nephropathy and Atherosclerosis Through Suppression of NF-κB and STAT Signaling Pathways in Diabetic Mice.

Heat shock proteins (HSPs) are induced by cellular stress and function as molecular chaperones that regulate protein folding. Diabetes impairs the function/expression of many HSPs, including HSP70 and HSP90, key regulators of pathological mechanisms involved in diabetes complications. Therefore, we investigated whether pharmacological HSP90 inhibition ameliorates diabetes-associated renal damage and atheroprogression in a mouse model of combined hyperglycemia and hyperlipidemia (streptozotocin-induced diabetic apolipoprotein E-deficient mouse). Treatment of diabetic mice with 17-dimethylaminoethylamino-17-demethoxygeldanamycin (DMAG, 2 and 4 mg/kg, 10 weeks) improved renal function, as evidenced by dose-dependent decreases in albuminuria, renal lesions (mesangial expansion, leukocyte infiltration, and fibrosis), and expression of proinflammatory and profibrotic genes. Furthermore, DMAG significantly reduced atherosclerotic lesions and induced a more stable plaque phenotype, characterized by lower content of lipids, leukocytes, and inflammatory markers, and increased collagen and smooth muscle cell content. Mechanistically, the renoprotective and antiatherosclerotic effects of DMAG are mediated by the induction of protective HSP70 along with inactivation of nuclear factor-κB (NF-κB) and signal transducers and activators of transcription (STAT) and target gene expression, both in diabetic mice and in cultured cells under hyperglycemic and proinflammatory conditions. In conclusion, HSP90 inhibition by DMAG restrains the progression of renal and vascular damage in experimental diabetes, with potential implications for the prevention of diabetes complications.

Decreased plasma endogenous soluble RAGE, and enhanced adipokine secretion, oxidative stress and platelet/coagulative activation identify non-alcoholic fatty liver disease among patients with familial combined hyperlipidemia and/or metabolic syndrome

ObjectiveIn patients with familial combined hyperlipidemia (FCHL), without metabolic syndrome (MS), occurrence of non-alcoholic fatty liver disease (NAFLD) is related to a specific pro-inflammatory profile, influenced by genetic traits, involved in oxidative stress and adipokine secretion.Among FCHL or MS patients, hyperactivity of the ligand–receptor for advanced glycation-end-products (RAGE) pathway, as reflected by inadequate protective response by the endogenous secretory (es)RAGE, in concert with genetic predisposition, may identify those with NAFLD even before and regardless of MS. MethodsWe cross-sectionally compared 60 patients with vs. 50 without NAFLD. Each group included patients with FCHL alone, MS alone, and FCHL plus MS. ResultsNAFLD patients had significantly lower plasma esRAGE, IL-10 and adiponectin, and higher CD40 ligand, endogenous thrombin potential and oxidized LDL. The effects of MS plus FCHL were additive. The genotypic cluster including LOX-1 IVS4-14A plus ADIPO 45GG and 256 GT/GG plus IL-10 10-1082G, together with higher esRAGE levels highly discriminate FCHL and MS patients not developing NAFLD. ConclusionsAmong FCHL or MS patients, noncarriers of the protective genotypic cluster, with lower esRAGE and higher degree of atherothrombotic abnormalities coincide with the diagnosis of NAFLD. This suggests an interplay between genotype, adipokine secretion, oxidative stress and platelet/coagulative activation, accelerating NAFLD occurrence as a proxy for cardiovascular disease.

Evaluation of clinical and angiographic characteristics of no reflow phenomenon after emergency PCI in AMI patients

Objective To investigate the clinical and angiographic characteristics of no reflow phenomenon after primary percutaneous coronary intervention (PCI) with acute myocardial infarction (AMI). Methods A total of 319 patients with AMI undergoing primary-PCI was divided into no-reflow and normal reflow groups. The incidence of no-reflow phenomenon, the clinical date, angiography findings, and surgical date were compared between two groups. Results No-reflow phenomenon occurred in forty(13.4%)of the patients after primary PCI. There was dramatic difference in combined hyperlipidemia, angina pectoris history before AMI, heart function ≥2 grades on admission, the length of the vascular lesions, vascular stenosis degree, blood clot load level, coronary artery opening time, and the expansion of the balloon between no-reflow and normal blood flow groups. Multiple logistic regression analysis identified that angina pectoris history before AMI, heart function classification on admission, high thrombus burden, the expansion of the balloon, and coronary artery opening time on angiography as independent predictors of no-reflow phenomenon. Conclusions The occurrence of no-reflow phenomenon after primary PCI was associated with high cholesterol history, no history of pre-infarction angina, heart function classification on admission, long vascular lesions, narrow degree of heavy, blood clots in the high load, coronary artery opened long time, and the expansion of the balloon more frequently. Key words: Myocardial infarction/TH/PP; Angioplasty, transluminal, percutaneous coronary

Contribution of mutations in low density lipoprotein receptor (LDLR) and lipoprotein lipase (LPL) genes to familial combined hyperlipidemia (FCHL): A reappraisal by using a resequencing approach

BackgroundDefective low-density lipoprotein receptor (LDLR) and lipoprotein lipase (LPL) alleles have been implicated in familial combined hyperlipidemia (FCHL). However, their contribution might have been influenced by diagnostic criteria. This study was aimed to reassess the frequency of rare and common variants in LDLR and LPL in FCHL individuals classified with stringent criteria. MethodsLDLR and LPL were resequenced in 208 FHCL and 171 controls. Variants were classified as loss- (LOF) or gain-of-function (GOF) based upon in silico prediction, familial segregation and available functional data. ResultsEight LOF variants were detected in LDLR, 6 of which were missense and 2 were predicted to disrupt normal splicing; all were present at heterozygous state. They were found in 10 FCHL but not in controls, thus indicating that 4.8% of FCHL individuals should be reclassified as FH. LDL-C (positive) and BMI (negative) were the strongest predictors of LDLR mutations with LDL-C 181 mg/dl being the best threshold for diagnosing the presence of dysfunctional LDLR alleles. The cumulative prevalence of definite LPL defective alleles (1 rare and 2 common heterozygous missense variants) was comparable between FCHL and controls (10.1% vs. 10.5%). Conversely, the LPL GOF variant p.Ser474* showed a lower frequency in FCHL than in controls (13.5% vs. 24.0%, p = 0.008). Overall, LOF LPL variants did not show a TG-modulating effect. ConclusionsOur findings indicate that, in well characterized FCHL individuals, variants in LDLR and LPL provide a small contribution to this dyslipidemia, thus limiting the need for such genetic testing.

Thioredoxins in cardiovascular disease.

Key thioredoxin (Trx) system components are nicotinamide adenine dinucleotide phosphate (NADPH), Trx reductase (TrxR), and Trx. TrxR catalyzes disulfide reduction in Trx with NADPH as cofactor. Because Trx is an antioxidant, oxidative stress results in an increase in Trx, which has a reduced disulfide component. If Trx is suppressed, oxidative stress in higher. In contrast a decrease in oxidative stress is associated with low Trx levels. Trx is involved in inflammation, apoptosis, embryogenesis, and cardiovascular disease (CVD). This review focuses on the Trx system in CVD. Abnormal Trx binding occurs in mouse familial combined hyperlipidemia; however, this has not been confirmed in humans. Congestive heart failure is a manifestation of many CVDs, which may be improved by attenuating oxidative stress through the suppression of Trx and decreased reactive oxygen species. Angiotensin II is associated with hypertension and other CVDs, and its receptor blockade results in decreased oxidative stress with reduced Trx levels. Inflammation is a major causative factor of CVDs, and myocarditis as an example, is associated with increased Trx levels. Vascular endothelial dysfunction has an association with CVD. This dysfunction is alleviated by hormone replacement therapy, which involves decreased oxidative stress and Trx levels. Diabetes mellitus has a major association with CVDs; increase in Trx levels may reflect insulin resistance. Identification of Trx system abnormalities may lead to innovative approaches to treat multiple CVDs and other pathologies.

Abstract 125: Small Dense LDL ApoB Is Catabolized More Slowly Than Large LDL ApoB in Subjects With Combined Hyperlipidemia, and Rosuvastatin Enhances Its Clearance

LDL consists of particles varying in size, density, and composition. Small dense LDL (sdLDL) cholesterol (C) has been shown to be a better predictor of coronary heart disease risk than total LDL-C. Intensive statin therapy significantly lowers sdLDL-C as well as large buoyant LDL (lbLDL)-C. We tested the hypotheses that lbLDL and sdLDL apoB100 have different catabolic rates, and that statin therapy enhances the fractional catabolism of apoB100 in both particles. Six subjects (3 men and 3 women; age 63±5 years [mean±SEM]; BMI 25.5±1.5 kg/m 2 ) with combined hyperlipidemia (triglycerides [TG] 191±50 mg/dl; LDL-C 160±16 mg/dl; HDL-C 43±6 mg/dl) received placebo and rosuvastatin 40 mg/day for 8 weeks each in sequential order. At the end of each phase, the kinetics of apoB100 in triglyceride rich lipoproteins ([TRL] d &lt;1.019 g/ml), lbLDL ( d =1.019-1.044 g/ml), and sdLDL ( d =1.044-1.063 g/ml) were determined using stable isotope methodology, gas chromatography-mass spectrometry, and multicompartmental modeling. Compared to placebo, rosuvastatin markedly decreased the plasma levels of LDL-C (52%; P =0.0002), TG (32%; P =0.06), and total apoB (42%; P &lt;0.0001). ApoB100 pool size in TRL, lbLDL, and sdLDL decreased 32±6%, 39±5%, 41±4%, respectively. These changes were attributable to significant ( P &lt;0.05) increases in apoB100 fractional catabolic rates in TRL (45±16%), lbLDL (131±66%), and sdLDL (97±32%). During both the placebo and rosuvastatin phases, sdLDL apoB100 was catabolized more slowly than lbLDL apoB100 ( P =0.01 and 0.004, respectively). Rosuvastatin did not alter apoB100 production rate or the percent of TRL apoB100 converted to each LDL subfraction. Proteomic analysis of the LDL particles indicated that rosuvastatin increased apoD abundance in lbLDL and decreased apoAIV abundance in sdLDL. No significant effects on other apolipoproteins were noted. These data indicate that sdLDL apoB100 is catabolized significantly more slowly than lbLDL apoB100 in dyslipidemic subjects on placebo or statin therapy. Maximal dose rosuvastatin decreases plasma apoB concentrations by enhancing apoB100 catabolism in TRL, lbLDL, and sdLDL and alters the distribution of minor apolipoproteins in LDL subfractions.

Primary hyperlipidemia in children: clinical, biochemistry characteristics and outcome

Patients and methods From 2007 to 2013, 30 children with primary hyperlipidemia were recruited and were treated with diet and/or lipid-lowering drug therapy at the National Hospital of Pediatrics, Hanoi, Vietnam. Clinical symptoms and biochemical finding, outcome of treatment were studied. Results: Among 30 cases from 28 families, 8 patients were mixed hyperlipidemia (MHL), 13 patients were hypertriglyceridemia (HT) and 9 patients were hypercholesterolemia (HC). Mean age of diagnosis was 5.5 years (1 month – 16 years). The rate of male/female was 13/17. Clinical manifestations included hepatomegaly (4 cases), xanthemas in the knees and elbows (5 cases), “creamy” blood (21 cases). Twenty cases were clinical asymptomatic. 8/28 patients had family history with hyperlipidemia and cardiovascular diseases. Serum cholesterol levels of HC group was 9.2 ± 4 mmol/l. Serum triglyceride level of HT group was 23.6 ± 9.9 mmol/l. MHL group had hypercholesterolemia (12.1 ± 4.5 mmol/l) and hypertriglyceridemia (20.3 ± 10.5 mmol/l). After interventions, HT group had the best outcome with serum triglyceride level was 10.1 ± 4.6 mmol/l, next to MHL group with serum cholesterole level was 5.8 ± 1.8 mmol/l, and serum triglyceride level was 9.5 ± 5.2 mmol/l; finally, serum cholesterole level of HC group was 12.4 ± 5.5 mmol/l. Five infants with HT had the best outcome of treatment: serum triglyceride level decreased from 19 57.6 mmol/l to 5 10 mmol/l. Two patients with HC had the worsen results (unchanged blood lipid level).

Short-term effects of a combined nutraceutical of insulin-sensitivity, lipid level and indexes of liver steatosis: a double-blind, randomized, cross-over clinical trial.

BackgroundOverweight subjects easily develop alterations of the glucose and lipid metabolism and are exposed to an increased cardiometabolic risk. This condition is potentially reversible through the improvement of dietary and behavioural habits. However, a well-assembled nutraceutical would be a useful tool to better improve the metabolic parameters associated to overweight and insulin resistance.MethodsTo evaluate the effect of a combined nutraceutical containing berberine, chlorogenic acid and tocotrienols, we performed a double blind, cross-over designed trial versus placebo, in 40 overweight subjects with mixed hyperlipidaemia. After the first 8 weeks of treatment (or placebo), patients were asked to observe a 2-week washout period, and they were then assigned to the alternative treatment for a further period of 8 weeks. Clinical and laboratory data associated to hyperlipidaemia and insulin resistance have been obtained at the baseline, at the end of the first treatment period, after the washout, and again after the second treatment period.ResultsBoth groups experienced a significant improvement of anthropometric and biochemical parameters versus baseline. However, total cholesterol, LDL cholesterol, triglycerides, non-HDL cholesterol, fasting insulin, HOMA-IR, GOT and Lipid Accumulation Product decreased more significantly in the nutraceutical group versus placebo.ConclusionsThis combination seems to improve a large number of metabolic and liver parameters on the short-term in overweight subjects. Further studies are needed to confirm these observations on the middle- and long-term.

Identification of the differentially expressed genes associated with familial combined hyperlipidemia using bioinformatics analysis.

The aim of the present study was to screen the differentially expressed genes (DEGs) associated with familial combined hyperlipidemia (FCHL) and examine the changing patterns. The transcription profile of GSE18965 was obtained from the NCBI Gene Expression Omnibus database, including 12 FCHL samples and 12 control specimens. The DEGs were identified using a linear models for microarray data package in the R programming language. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was also performed. Protein-protein interaction (PPI) networks of the DEGs were constructed using the EnrichNet online tool. In addition, cluster analysis of the genes in networks was performed using ClusterONE. A total of 879 DEGs were screened, including 394 upregulated and 485 downregulated genes. Enrichment analysis identified four important KEGG pathways associated with FCHL: One carbon pool by folate, α-linolenic acid metabolism, asthma and the glycosphingolipid biosynthesis-globo series. GO annotation identified 12 enriched biological processes, including one associated with hematopoiesis and four associated with bone cell differentiation. This identification was in accordance with clinical data and experiments into hyperlipidemia and bone lesions. Based on PPI networks, these DEGs had a close association with immune responses, hormone responses and cytokine-cytokine receptors. In conclusion, these DEGs may be used as specific therapeutic molecular targets in the treatment of FCHL. The present findings may provide the basis for understanding the pathogenesis of FCHL in future studies. However, further experiments are required to confirm these results.

Changes of serum lipids in patients with Bietti crystalline dystrophy

Background Bietti crystalline dystrophy (BCD) is a congenital and autosomal recessive hereditary eye disease characterized by multiple glistening intraretinal crystals scattered over the fundus.Studies determined abnormality of fatty acid metabolism probably is associated with BCD.However, the study on the alteration of blood lipid level in BCD patients is rare. Objective This trail was to study the change of serum lipids in BCD patients. Methods A total of 50 patients with bilateral BCD and 50 matched healthy volunteers were included from November 2011 to March 2013 in Beijing Tongren Eye Center with the approval of Ethic Committee of Beijing Tongren Hospital.Written informed consent was obtained from each subject before any medial examination.Peripheral blood of 3 ml was collected from the subjects.The serum concentrations of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were measured and analyzed.The examination outcome was identified based on the criteria of China Adult Dyslipidemia Prevention Guideline (Version 2007). Results Abnormality of serum lipid content was detected in 58.00% patients (29/50), and hypertriglyceridemia and hypercholesteremia were in 34.48% (10/29), respectively, and mixed hyperlipidaemia was in 27.59 % (8/29).The serum levels of TG, TC and LDL-C were (1.63±1.19) mmol/L, (5.10±1.05) mmol/L and (3.27±0.97) mmol/L in the BCD group, which were significantly higher than (0.93±0.33) mmol/L, (4.33±0.56) mmol/L, (2.63±0.51) mmol/L of the normal group (t=4.036, 4.496, 4.095, all at P=0.000). Conclusions The serum lipid levels elevate in BCD patients, which might be related to the occurrence of BCD. Key words: Choroid Diseases/congenital; Fundus Oculi; Humans; Pigment Epithelium of Eye; Retinal Degeneration/congenital; Lipids/blood; Bietti crystalline dystrophy

Hypertriglyceridemia in the genomic era: a new paradigm.

Hypertriglyceridemia (HTG) is a highly prevalent condition that is associated with increased cardiovascular disease risk. HTG may arise as a result of defective metabolism of triglyceride-rich lipoproteins and their remnants, ie, impaired clearance, or increased production, or both. Current categorization of HTG segregates primary and secondary cases, implying genetic and nongenetic causes for each category. Many common and rare variants of the genes encoding factors involved in these pathways have been identified. Although monogenic forms of HTG do occur, most cases are polygenic and often coexist with nongenetic conditions. Cumulative, multiple genetic variants can increase the risks for HTG, whereas environmental and lifestyle factors can force expression of a dyslipidemic phenotype in a genetically susceptible person. HTG states are therefore best viewed as a complex phenotype resulting from the interaction of cumulated multiple susceptibility genes and environmental stressors. In view of the heterogeneity of the HTG states, the absence of a unifying metabolic or genetic abnormality, overlap with the metabolic syndrome and other features of insulin resistance, and evidence in some patients that accumulation of numerous small-effect genetic variants determines whether an individual is susceptible to HTG only or to HTG plus elevated low-density lipoprotein cholesterol, we propose that the diagnosis of primary HTG and further delineation of familial combined hyperlipidemia from familial HTG is neither feasible nor clinically relevant at the present time. The hope is that with greater understanding of genetic and environmental causes and their interaction, therapy can be intelligently targeted in the future.