Serum Lipid Variables Research Articles

The Utility of Serial Lipid Measurements as a Potential Predictor of Sepsis Outcome: A Prospective Observational Study in a Tertiary Care Hospital.

Sepsis is the major cause of morbidity and mortality for patients admitted to an intensive care unit worldwide. Currently, procalcitonin (PCT) is a widely used prognostic marker for sepsis. The high cost of estimating Procalcitonin limits its utility in all health facilities. Lipid profile, being a frequently done routine investigation, is studied in sepsis patients to predict the prognosis of sepsis. This study was aimed to assess the association between lipid profile parameters, procalcitonin and clinical outcomes in patients with sepsis. It is a prospective observational study conducted in a tertiary care hospital in the Department of Biochemistry in collaboration with the Intensive Care Unit (ICU). We included 80 sepsis patients from medical and surgical ICUs. Among them, 59 (74%) survived and 21 (26%) expired. Serum lipid profile, procalcitonin and variables required for APACHE II score are measured at two intervals, one during admission and on day 5. All the parameters were compared between the survivors and the non-survivors. Serum PCT levels were reduced on day 5 [3.32 (1.27-11.86)] compared to day 0 [13.42 (5.77-33.18)] in survivors. In survivors, Total Cholesterol, LDL-C and Non-HDL-C were significantly elevated on day 5 compared to day 0. In non-survivors, HDL-C significantly decreased on day 5. Between survivors and non-survivors, HDL-C significantly decreased on day 5 (23.88 ± 10.19 vs 16.67 ± 8.27 mg/dl). A Negative correlation was observed between HDL-C & PCT. Serum Lipid profile levels, namely Total cholesterol, HDL-C and LDL-C, have possible associations with the severity of sepsis. HDL-C have a negative association with the clinical scoring system in sepsis patients. Overall, the findings from our study suggest that lipid profile parameters have possible implications in predicting the outcome of patients with sepsis.

Association of exposures to serum terpenes with the prevalence of dyslipidemia: a population-based analysis.

This study sought to examine hitherto unresearched relationships between serum terpenes and the prevalence of dyslipidemia. Serum terpenes such as limonene, α-pinene, and β-pinene from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) were used as independent variables in this cross-sectional study. Continuous lipid variables included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), residual cholesterol (RC), and apolipoprotein B (Apo B). Binary lipid variables (elevated TC, ≥5.18 mmol/L; lowered HDL-C, <1.04 mmol/L in men, and <1.30 mmol/L in women; elevated non-HDL-C, ≥4.2 mmol/L; elevated TG, ≥1.7 mmol/L; elevated LDL-C, ≥3.37 mmol/L; elevated RC, ≥1.0 mmol/L; and elevated Apo B, ≥1.3 g/L) suggest dyslipidemia. The relationships between the mixture of serum terpenes with lipid variables were investigated using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR). The study for TC, HDL-C, and non-HDL-C included a total of 1,528 people, whereas the analysis for TG, LDL-C, RC, and Apo B comprised 714 participants. The mean age of the overall participants was 47.69 years, and 48.77% were male. We found that tertiles of serum terpene were positively associated with binary (elevated TC, non-HDL-C, TG, LDL-C, RC, Apo B, and lowered HDL-C) and continuous (TC, non-HDL-C, TG, LDL-C, RC, and Apo B, but not HDL-C) serum lipid variables. WQS regression and BKMR analysis revealed that the mixture of serum terpenes was linked with the prevalence of dyslipidemia. According to our data, the prevalence of dyslipidemia was correlated with serum concentrations of three terpenes both separately and collectively.

Association of Single Nucleotide Polymorphism of Apo A-1 Gene and Lipid Variables in Patients with Myocardial Infarction: A Case-control Study

Introduction: Genetic and environmental factors play a significant role in the development of cardiovascular disease (CVD). With advancements in molecular techniques, it is now possible to study genes that may provide evidence of the role of genetic factors in coronary artery disease (CAD). Genetic variants of the Apo A-1 gene might play an important role in regulating lipid profiles and their alteration, leading to the subsequent development of myocardial infarction (MI). Aim: The aim of this study was to evaluate the association between C+83T sequence variations in the first intron of the Apo A-1 gene and lipid variables in patients with MI. Materials and Methods: A case-control study was conducted at the Department of Biochemistry in association with the Department of Cardiology, Kilpauk Medical College Hospital, Chennai, Tamil Nadu, India, from October 2013 to March 2014. The study included 52 MI cases and 52 age-, gender-, and risk factor-matched controls. Fasting venous blood samples were collected from each patient, and routine investigations, lipid profile assessments, and polymorphic studies were carried out. Allele frequencies between cases and controls were compared using the Chi-square test. Analysis of variance (ANOVA) was performed to determine the association between fasting serum lipid variables and allele distribution. Results: Both study groups were matched for age, gender, and risk factors such as alcohol consumption, smoking, hypertension (HT), and diabetes mellitus (DM). The results were compared and found to be statistically insignificant. Genotype analysis between the groups disclosed that the TT homozygous genotype was more prevalent in cases, while the 'CC' genotype was more prevalent in controls, and the CT genotype was approximately equal in both cases and controls. The genotype difference between cases and controls was statistically significant (p-value=0.006). The 'T' allele frequency was higher among cases (0.36) compared to controls (0.13), while the frequency of the 'C' allele was higher among controls (0.86) compared to cases (0.63). In the CC genotype, there was a higher mean value of Apo A-1 and a lower ApoB/ Apo A-1 ratio compared to the TT genotype. It was observed that carriers of the C allele and T allele showed no statistical difference in lipid variables except for high-density lipoprotein (HDL). Conclusion: This study found a significantly increased T allele frequency in cases compared to controls, suggesting that the presence of the T allele in the C+83T (first intron) of the Apo A-1 gene may increase the risk of developing MI.

Associations of thiocyanate, nitrate, and perchlorate exposure with dyslipidemia: a cross-sectional, population-based analysis.

The aim of this study was to assess the associations of urinary thiocyanate, nitrate, and perchlorate concentrations with dyslipidemia, individually and in combination, which has not previously been studied. Data from the 2001-2002 and 2005-2016 National Health and Nutrition Examination Surveys (NHANES) were analyzed in this cross-sectional study. The dependent variables were continuous serum lipid variables (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], non-HDL-C, and apolipoprotein B [Apo B]) and binary serum lipid variables, with the latter reflecting dyslipidemia (elevated TG, ≥ 150mg/dL; elevated TC, ≥ 200mg/dL; elevated LDL-C, ≥ 130mg/dL; lowered HDL-C, < 40mg/dL in men and < 50mg/dL in women; elevated non-HDL-C, ≥ 160mg/dL; and elevated Apo B, ≥ 130mg/dL). Multivariate logistic, linear, and weighted quantile sum (WQS) regression analyses were used to explore the associations of thiocyanate, nitrate, and perchlorate with the continuous and binary serum lipid variables. The linearity of the associations with the binary serum lipid variables was assessed using restricted cubic spline (RCS) regression. A total of 15,563 adults were included in the analysis. The multivariate linear and logistic regression analyses showed that thiocyanate was positively associated with multiple continuous (TG, TC, LDL-C, non-HDL-C, and Apo B, but not HDL-C) and binary (elevated TG, TC, LDL-C, and non-HDL-C) serum lipid variables, whereas perchlorate was negatively associated with elevated LDL-C. Multivariate RCS logistic regression revealed a linear dose-response relationship between thiocyanate and elevated TG, TC, LDL-C, non-HDL-C, and Apo B, but a nonlinear relationship with lowered HDL-C (inflection point = 1.622mg/L). WQS regression showed that a mixture of thiocyanate, nitrate, and perchlorate was positively associated with all binary serum lipid variables except for Apo B. Our findings indicate that urinary thiocyanate, nitrate, and perchlorate concentrations, individually and in combination, were associated with dyslipidemia.

Association of Serum Lipid Levels with Parkinson’s Disease: A Case-Control Study

Background: Parkinson’s disease (PD) is a common neurodegenerative disorder. Many hypotheses have been put forward for PD pathogenesis including role of lipid metabolism. Methods: This case control study was carried out in the department of neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from April 2018 to September 2019. A total of 90 persons were enrolled as study population after satisfying inclusion and exclusion criteria. Among them, 42 PD patients were grouped as cases and 48 healthy persons were controls. Results: We have compared the mean (±SD) value (mg/dl) of serum lipid variables among the cases and the controls. Serum total cholesterol in PD patients was found lower than that of control group (176.88 ± 41.12 vs 209.27 ± 43.69 mg/dl) which was statistically significant (p = 0.001) and mean (±SD) value (mg/dl) of serum LDL-C in PD patients was also found significantly lower than that of control group (107 .44 ± 39.04 vs 127.40 ± 37.83 mg/dl, p = 0.017). Serum TG levels were also significantly lower among PD patients than that of controls (152.40 ±77.86 vs 206.71 ±94.76 mg/dl, p = 0.04). Serum high-density lipoprotein cholesterol (HDL-C) levels were statistically similar among cases and controls (39.81 ± 9.79 vs 39.33 ±12.21 mg/dl, p = 0.840). Conclusion: There is an association between low serum TC, LDL-C and TG levels with PD. Further prospective studies are necessary to confirm the association. Bangladesh Journal of Neuroscience 2018; Vol. 34 (2): 66-71

Can TG/HDL Ratio be an Accurate Predictor in the Determination of the Risk of Cerebrovascular Events in Youngsters?

Objectives:There is good evidence that shows that modification of modifiable risk factor will reduce the risk of stroke. Hyperlipidemia is one of these risk factors. Studies have shown that nontraditional serum lipid variables may be better predictors of vascular risk rather than others.The objective of the present study was to assess the relationships of traditional and nontraditional serum lipid measurements between young and elder patients with stroke and healthy young adults.Methods:One hundred twelve young patients with ischemic stroke, 113 healthy adults, and 110 patients with ischemic stroke aged >45 years were included in the study. Laboratory tests for total cholesterol (TC), its fractions, and triglycerides (TGs) were performed using standard techniques, and we computed four nontraditional lipid variables.Statistical analyses were performed using chi-square test, Student’s t-test, and SPSS version 16.0 software. A p value of <0.05 was considered statistically significant.Results:The mean age of 112 young patients with stroke was 38.46±5.96 years. There were 63 male and 49 female patients. Measurements of lipid parameters were as follows: low-density lipoprotein (LDL) 121.42±36.56 mg/dl, high-density lipoprotein (HDL) 38.84±12.47 mg/dl, TG 186.10±176.14 mg/dl, TC 194.76±45.35 mg/dl, LDL/HDL 3.39±1.46, TG/HDL 5.44±6.36, and TC/HDL 5.40±6.36. All lipid measurements were significantly higher in young patients with stroke than in healthy adults.The mean age of 110 patients with stroke aged >45 years was 69.53±12.34 years. There were 63 male and 47 female patients. Measurements of lipid parameters were as follows: LDL 125.18±35.97 mg/dl, HDL 41.47±14.16 mg/dl, TG 117.53±59.03 mg/dl, TC 190.16±42.96 mg/dl, LDL/HDL 3.32±1.55, TG/HDL 3.46±3.43, and TC/HDL 5.01±2.08. TG level and TG/HDL ratio were significantly higher in young patients with stroke than in older cases.Conclusion:All lipid measurements were significantly higher in young patients with ischemic stroke than in young healthy adults. TG level and TG/HDL ratio were significantly higher in male than in female patients. In addition, TG level and TG/HDL ratio were significantly higher in young patients with stroke than in older cases. As the TG/HDL ratio has proven to be a highly significant independent prognostic predictor of stroke, it should be calculated in young patients with ischemic stroke.

12주간의 걷기운동과 키네시오 테이핑 복합처치가 뇌졸중 환자의 혈중 염증인자 및 지질성분에 미치는 영향

이 연구는 뇌졸중 환자를 대상으로 12주간 걷기운동과 키네시오테이핑 복합처치를 하여 혈중염증인자 및 혈중지질의 변화를 분석하여 다음과 같은 결론을 얻었다. 혈중 염증반응에서 CK농도를 분석한 결과 실험전과 4주, 8주에서는 유의한 차가 나타나지 않았지만 12주후에서는 유의한 차가 나타났고, CG과 WG, CG과 TWG에서 그룹간 유의한 차이가 나타났다. LDH농도를 분석한 결과 8주후와 12주후 시기에서 CG과 WG, CG과 TWG에서 그룹간 유의한 차이가 나타났고, CRP농도를 분석한 결과 WG과 TWG에서 시기간 유의한(p.001)차이가 나타났으며, 시기별 그룹간 차이에서 CG와 WG, CG와 TWG에서 4주후, 8주후, 12주후 모두 유의한(p.01) 차이가 나타났다.BR 혈중지질에서 TC와 TG농도를 4주마다 분석한 결과 실험전과 4주, 실험전과 8주에서는 유의한 차이가 나타나지 않았지만 12주에서는 유의한 차이가 나타났고, 그룹별에서는 CG과 WG, CG과 TWG에서 유의한 차이가 나타났다.BR 이상의 결과로 보아 본 연구에서는 뇌졸중으로 인한 편마비 환자에게 걷기운동과 키네시오테이핑의 복합처치가 혈중염증인자, 혈중지질에 효과적임을 알 수 있었다.

Integrative variants, haplotypes and diplotypes of the CAPN3 and FRMD5 genes and several environmental exposures associate with serum lipid variables

To determine whether the integrative variants, haplotypes and diplotypes of the calpain 3 (CAPN3) and the FERM domain containing 5 genes (FRMD5) and several environmental exposures are associated with an implication in lipid homeostasis, which are associated with cardiovascular risk. Genotyping of the CAPN3 rs4344713 and FRMD5 rs524908 was performed by Sanger sequencing in 1,640 subjects (Jing, 819 and Han, 821). Multivariate analyses of covariance models that adjusted by age, gender, body mass index (BMI), blood pressure and lifestyle (smoking and drinking), were constructed using variants, haplotypes and diplotypes of the CAPN3 rs4344713 and FRMD5 rs524908 as predictors and changes in lipid variables. Significant associations with low-density lipoprotein cholesterol and apolipoprotein (Apo) B were found. Linkage disequilibrium with each other showed the haplotype-phenotype associations with triglyceride and ApoA1. This study also suggested pleiotropic associations of the CAPN3-FRMD5 diplotypes with lipid variables. As potential confounders, diastolic blood pressure (DBP) and BMI were significantly associated with lipid variables. We conclude that integrative variants, haplotypes and diplotypes of the CAPN3 rs4344713 and FRMD5 rs524908, as well as DBP and BMI are associated with serum lipid variables in the Jing and Han populations.

Common Variants in Cholesterol Synthesis– and Transport–Related Genes Associate with Circulating Cholesterol Responses to Intakes of Conventional Dairy Products in Healthy Individuals

Background: Dairy intake has been associated with varying impacts on circulating cholesterol concentrations across nutritional epidemiology and intervention studies, with findings attributed mainly to differences in the nature of dairy products consumed or study designs. The contribution of the genomic architecture to such observations has yet to be revealed.Objective: We assessed the impact of multiple common genetic variations in cholesterol-related genes on responses of serum cholesterol to the recommended amount of dairy product intake in Canada.Methods: In a multicenter, randomized crossover design, 101 normolipidemic adults (n = 29 men and 72 women), with a mean ± SD age of 41.7 ± 16.7 y and a body mass index (BMI, in kg/m2) of 25.9 ± 4.3 consumed 3 servings/d of dairy [375 mL 1% milk-fat (MF) milk, 175 g 1.5% MF yogurt, and 30 g of 34% MF cheese] or energy-matched control products (juice, cashews, and cookies) provided within a prudent background diet for 4 wk each, separated by a 4- to 8-wk washout period. Serum lipid variables were determined by standard enzymatic methods by using an autoanalyzer. Candidate single nucleotide polymorphisms were assessed by TaqMan genotyping assay.Results: The responsiveness of serum total cholesterol (TC) and LDL cholesterol to the dairy compared with the control diet was associated with individuals’ genotypes. The cholesterol transport gene ATP-binding cassette subfamily G, member 5 (ABCG5) rs6720173-GG homozygotes had higher concentrations of TC (+0.18 mmol/L; P = 0.0118) and LDL cholesterol (+0.17 mmol/L; P = 0.0056) relative to C-allele carriers (−0.07 and −0.06 mmol/L, respectively). The bile acid synthesis gene cholesterol 7α-hydroxylase (CYP7A1) rs3808607-G-allele carriers had higher TC (+0.20 to +0.28 mmol/L; P = 0.0026) and LDL cholesterol (+0.19 mmol/L for GT genotype; P = 0.0260) relative to TT homozygotes (−0.11 and −0.03 mmol/L, respectively). In addition, the cholesterol synthesis gene 7-dehydrocholesterol reductase (DHCR7) rs760241-A-allele carriers had higher LDL cholesterol (+0.26 mmol/L; P = 0.0399) relative to GG homozygotes (+0.06 mmol/L).Conclusion: Genetic variations in ABCG5, CYP7A1, and DHCR7 may contribute to differing responses of serum cholesterol to dairy intake among healthy adults. This trial was registered at clinicaltrials.gov as NCT01444326.

Elevated Lipid Profiles in Patients with Acute Transverse Myelitis

Background: The associations and clinical relevance of serum lipid profiles in patients with acute transverse myelitis (ATM) are unknown. Our study aimed at investigating the status of serum lipid variables (including total cholesterol (TC), triglycerides (TGs), high/low density lipoproteins (HDL/LDL), apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB) and cholesterol to HDL ratio) in ATM, and to explore whether there was a correlation between serum lipid levels and disease characteristics of ATM. Methods: We retrospectively evaluated serum lipid levels of 92 patients with ATM, 43 with multiple sclerosis (MS) on relapse and 112 healthy controls (HC). The changes of serum lipid profiles were analyzed. Results: We found that ATM patients had higher serum TC, TG, LDL levels and T/H ratio than HC, but had lower levels of serum ApoA-I and ApoB. Besides, there were no significant differences between ATM and MS on relapse (except ApoB). Third, longer disease duration was associated with higher TG; higher HDL was associated with a trend for lower Expanded Disability Status Scale scores. Conclusions: Our findings showed that serum lipid levels were elevated in patients with ATM, among serum TG and HDL might be associated with clinical features. These results illustrate that a long-term follow-up and regular monitoring of serum lipid profiles are important for ATM patients.

GW26-e1011 The relationship between the composite index of the serum bilirubin and serum lipid variables and the serum fibrinogen level and the severity of coronary heart disease

To explore the relationship between the composite index of the serum bilirubin and serum lipid variables, the serum fibrinogen(FIB) level and the severity of coronary heart disease. To investigate whether it is more significant for the composite index of the serum bilirubin and serum lipid variables

Nontraditional serum lipid variables and recurrent stroke risk.

Expert consensus guidelines recommend low-density lipoprotein cholesterol as the primary serum lipid target for recurrent stroke risk reduction. However, mounting evidence suggests that other lipid parameters might be additional therapeutic targets or at least also predict cardiovascular risk. Little is known about the effects of nontraditional lipid variables on recurrent stroke risk. We analyzed the Vitamin Intervention for Stroke Prevention study database comprising 3680 recent (<120 days) noncardioembolic stroke patients followed up for 2 years. Independent associations of baseline serum lipid variables with recurrent ischemic stroke (primary outcome) and the composite end point of ischemic stroke/coronary heart disease/vascular death (secondary outcomes) were assessed. Of all variables evaluated, only triglycerides/high-density lipoprotein cholesterol (HDL-C) ratio was consistently and independently related to both outcomes: compared with the lowest quintile, the highest triglycerides/HDL-C ratio quintile was associated with stroke (adjusted hazard ratio, 1.56; 95% confidence interval, 1.05-2.32) and stroke/coronary heart disease/vascular death (1.39; 1.05-1.83), including adjustment for lipid modifier use. Compared with the lowest quintile, the highest total cholesterol/HDL-C ratio quintile was associated with stroke/coronary heart disease/vascular death (1.45; 1.03-2.03). Low-density lipoprotein cholesterol/HDL-C ratio, non-HDL-C, elevated triglycerides alone, and low HDL-C alone were not independently linked to either outcome. Of various nontraditional lipid variables, elevated baseline triglycerides/HDL-C and total cholesterol/HDL-C ratios predict future vascular risk after a stroke, but only elevated triglycerides/HDL-C ratio is related to risk of recurrent stroke. Future studies should assess the role of triglycerides/HDL-C as a potential therapeutic target for global vascular risk reduction after stroke.

Effect of rosiglitazone on capillary density and angiogenesis in adipose tissue of normoglycaemic humans in a randomised controlled trial.

Recent reports of decreased capillary density in the adipose tissue of obese individuals suggest that an imbalance of angiogenesis and adipogenesis may, in part, underlie insulin resistance. This study aimed to determine whether the insulin-sensitising peroxisome proliferator-activated receptor γ (PPARγ) activator rosiglitazone affects adipose tissue vascularisation in normal humans. A randomised, parallel-group, investigator-blinded placebo-controlled trial was conducted with normoglycaemic volunteers with BMI 27-43, recruited from the community at the University of Massachusetts Medical School, Worcester, MA, USA. Peri-umbilical adipose tissue biopsies were obtained before and after treatment for 6 weeks with rosiglitazone (8 mg once daily) or placebo, which were randomly allocated from a sequentially numbered list. The primary outcomes were adipocyte size and capillary density measured by immunohistochemistry, and angiogenic potential assessed by capillary sprout formation in Matrigel. Secondary outcomes were serum adiponectin, glycaemic, lipid and liver function variables. A total of 35 individuals fulfilling the inclusion criteria were randomised, and complete before-vs-after analyses were achieved in 30 participants (13 and 17, placebo and rosiglitazone, respectively). Significant differences, assessed by paired two-tailed Student t tests, were seen in response to rosiglitazone for adipocyte size (3,458 ± 202 vs 2,693 ± 223 μm(2), p = 0.0049), capillary density (5.6 ± 0.5 vs 7.5 ± 0.5 lumens/field, p = 0.0098), serum adiponectin (14.3 ± 1.5 vs 28.6 ± 3.0 ng/ml, p < 0.0001) and alkaline phosphatase (1.04 ± 0.07 vs 0.87 ± 0.05 μkat/l, p = 0.001). A difference in angiogenic potential before and after treatment between the placebo and rosiglitazone groups was also seen (-23.88 ± 14 vs 13.42 ± 13, p = 0.029, two-tailed Mann-Whitney test). Significant effects on adipose tissue vascular architecture occur after a short period of treatment with rosiglitazone in individuals with normal glucose tolerance. Improved adipose tissue vascularisation may, in part, mediate the therapeutic actions of this class of drugs. ClinicalTrials.gov NCT01150981 The study was funded by National Institutes of Health grant DK089101 to S. Corvera, and by pilot funding from the University of Massachusetts (UMASS) Center for Clinical Translational Sciences (M. Thompson, S. Malkani and S. Corvera). Morphology core services were supported by UMASS Diabetes Endocrine Research Center (DERC) grant DK32520.

Effect of dietary fiber of “Rihane” barley grains and azoxymethane on serum and liver lipid variables in Wistar rats

The aim of the present study is to evaluate the effects of diet enriched with dietary fiber of barley variety "Rihane" and azoxymethane on serum and liver lipid variables in male rats. Forty male rats were divided into four groups and fed on control diet or experimental diet that contained control enriched with dietary fiber of barley variety "Rihane". Animals were injected with saline (controls) or azoxymethane (20 mg/kg body weight s.c.) at 7 and 8 weeks of age. The experimental diet significantly decreased cholesterol level compared with the control diet. Rats fed with BR diet significantly increased the serum high-density lipoprotein (HDL) cholesterol and significantly decreased low-density lipoprotein (LDL) cholesterol concentrations. The experimental diet decreased the atherogenic index (p < 0.05) compared with the control diet. Whereas the azoxymethane induced a significant increase of liver lipid, serum LDL and triglyceride concentrations, but it caused a significant reduction of HDL. Consequently, the ratio of HDL/TC decreased significantly compared with the control (p < 0.05). Accordingly, these results indicated that the diet enriched with dietary fiber of barley variety "Rihane" could be effective in decreasing the atherogenic risk factors in rats whereas the use of the azoxymethane as colon-specific carcinogen substance altered the lipid metabolism.

Beyond LDL Cholesterol, a New Role for PCSK9

Elevated low-density lipoprotein cholesterol (LDLC) levels in the plasma is the most important causative factor of atherosclerosis and associated ischemic cardiovascular diseases. The LDL receptor (LDLR) is the preferential pathway through which LDLs are cleared from the circulation. LDLs bound to the LDLR are internalized into clathrin-coated pits and subsequently undergo lysosomal degradation, whereas the LDLR is recycled back to the plasma membrane. See accompanying article on page 1333 Familial hypercholesterolemia (FH) is an autosomal dominant disorder associated with elevated LDL levels and premature coronary heart disease. FH is caused primarily by mutations of the LDLR or of apolipoprotein B100 (apoB100), the protein component of LDL that interacts with the LDLR. In 2003, “gain of function” mutations on a newly identified gene, proprotein convertase subtilisin/kexin type 9 ( PCSK9), were associated with FH. In 2005, a causative association was established between “loss of function” mutations in PCSK9 and low LDLC levels in 2% of the African-American population. The coronary heart disease risk in these individuals was reduced by 88%. As a result of these landmark studies (reviewed in Reference 1), PCSK9 became the subject of intensive research to discover the underlying mechanisms. PCSK9 is a serine protease mainly expressed in the liver and the intestine. It acts by reducing the amount of LDLR in hepatocytes. This was demonstrated in vitro and in mouse models …

Genetic Variation in the FAAH Gene and Metabolic Syndrome–related Phenotypes

TO THE EDITOR: We read with great interest the article “Variants in the CNR1 and the FAAH Genes and Adiposity Traits in the Community” by Lieb et al. about a lack of association of common variants of the CNR1 and FAAH genes with surrogate measures of adiposity in a large community-based sample of individuals (1). The authors performed a comprehensive analysis of common variation across these two genes and observed no evidence for association of any variant with BMI, waist circumference, and visceral adipose tissue volume. In a smaller (n = 420) but well-characterized sample of adult men of self-reported European ancestry (aged 34.4 ± 0.4 years, mean ± s.e.), selected from a population-based study in Argentinean people, we explored the role of the C/T rs6703669-FAAH variant in the genetic susceptibility of metabolic syndrome–related phenotypes. The variant was selected as a tagSNP capturing common variation in the promoter region of the gene (pair-wise approach at r2 = 0.8, minor allele frequency >10%). Genotyping was performed by allele-specific PCR and genotypes were in Hardy–Weinberg equilibrium. In agreement with Lieb et al., we found no evidence of association between the variant and any of the obesity-related phenotypes: BMI as a continuous trait (logarithmically transformed) P = 0.9, waist circumference P = 0.25, obesity status as a discrete trait P = 0.24, and measurement of body fat content by bioelectrical impedance P = 0.4. Nevertheless, when we analyzed the serum lipid variables in relation to the rs6703669, a significant association was observed with plasma levels of triglycerides: homozygous CC 105.1 ± 5.9, heterozygous CT 131.3 ± 7.5 and homozygous TT 119.2 ± 15.5 mg/dl, P < 0.015, adjusted by log-transformed age and BMI. Accordingly, hypertriglyceridemia evaluated as a discrete trait (plasma triglycerides ≥150 mg/dl), also showed significant association with the variant (OR per T allele: 1.31, 95% CI 1.04–1.66, P < 0.022). Finally, we evaluated the possible association of the rs6703669 and other metabolic syndrome–related phenotypes and observed a significant association with arterial hypertension (dichotomized as a discrete trait): OR per T allele: 1.43, 95% CI 1.06–1.95, P = 0.01, after adjusting by log-transformed age and BMI. Similarly, the quantitative trait diastolic arterial blood pressure was significantly associated with the variant (P < 0.023): homozygous CC: 74.2 ± 0.6, heterozygous CT: 76.2 ± 0.7 and homozygous TT: 78.1 ± 1.7 mm Hg. In summary, the findings of Lieb et al. can also be generalized to Argentinean population, as an example of replication in a different group of European descent. However, these results do not exclude other possible effects of the variants of the FAAH on metabolic syndrome–related phenotypes, for instance arterial blood pressure or plasma triglycerides. These data, which need to be confirmed in larger samples, may be of interest because the use of FAAH as a therapeutic target in hypertension is under evaluation not only because of the potential beneficial effect of endocannabinoid-related drugs on arterial blood pressure but also on the development of the hypertensive cardiac hypertrophy (2,3). This study was partially supported by PICT 05-25920 (Agencia Nacional de Promoción Científica y Tecnológica). A.L.B., S.S., C.G., and C.J.P. belong to Consejo Nacional de Investigaciones Científicas y Técnicas. A.L.B. is recipient of a Health Ministry Fellowship (Beca Ramón Carrillo-Arturo Oñativia Ministerio de Salud y Ambiente de la Nación) Convocatoria 2008. The authors declared no conflict of interest.

Alcohol intake modulates the genetic association between HDL cholesterol and the PPARγ2 Pro12Ala polymorphism

The peroxisome proliferator-activated receptor gamma (PPARgamma) Pro12Ala polymorphism affects plasma lipids, but to what extent alcohol intake interferes with this association remains unknown. We randomly recruited 251 nuclear families (433 parents and 493 offspring) in the framework of the European Project on Genes in Hypertension study and genotyped 926 participants in whom all serum lipid variables and information on alcohol consumption were available for PPARgamma2 Pro12Ala. Genotype-phenotype relations were assessed using generalized estimating equations (GEE) and a quantitative transmission disequilibrium test (QTDT). The Ala12 allele was more frequent in Novosibirsk (0.17) than in Cracow (0.12) and Mirano (0.11) (P < 0.01). Using GEE (P = 0.03) or QTDT (P = 0.007), Italian offspring carrying the Ala12 allele had higher serum HDL cholesterol than noncarriers. HDL cholesterol levels were on average 0.086 mmol/l (P = 0.001) higher in drinkers than in nondrinkers. Compared with Pro12 homozygotes, Ala12 allele carriers consuming alcohol had higher serum total and HDL cholesterol, with the opposite trend occurring in nondrinkers. This genotype-alcohol interaction was independent of the type of alcoholic beverage and more pronounced in moderate than in heavy drinkers. We conclude that alcohol intake modulates the relation between the PPARgamma2 Pro12Ala and HDL cholesterol level and that, therefore, the Pro12Ala polymorphism, pending confirmation of our findings, might affect cardiovascular prognosis.

Effect of dietary conjugated linoleic acid (CLA) on carcass quality, serum lipid variables and histopathological changes of broiler chickens infected with aflatoxin B1

Three dietary inclusion rates of CLA (0, 2 and 4 g/kg feed) and aflatoxin B1 (0, 200 and 300 μg/kg feed) were tested in a 3 x 3 factorial experimental design on a total of 99 Ross-308 male broiler chickens from 1 to 42 days of age. The objective of this study was to determine the effect of dietary conjugated linoleic acid (CLA) on carcass characteristics, serum lipid variables and histopathological properties in broiler chickens receiving a diet containing aflatoxin B1 (AFB1). Carcass yield, abdominal fat weight and abdominal fat percentage were not significantly influenced by dietary CLA, AFB1 or CLA + AFB1. Altered serum lipid measurements induced by AFB1 treatments included increased serum cholesterol and triglyceride concentrations, and decreased serum concentration of high density lipoprotein (HDL). Serum HDL concentration was increased in birds supplemented with 2 and 4 g CLA/kg diet compared with the control group. However, CLA + AFB1 did not significantly affect these parameters compared to the groups that received AFB1 alone. Aflatoxin B1 administration induced degenerative changes in the liver tissue, but dietary CLA supplementation offered protection to the livers against these changes. Aflatoxin B1 residues were not detected in any breast tissues collected from the broiler carcasses. Our results suggest that CLA provided protection against the negative effects of liver damage induced by AFB1 in broiler chickens. Furthermore, dietary CLA supplementation increased serum HDL levels. Keywords : Aflatoxin B1; conjugated linoleic acid;carcass quality; hepatotoxicity; serum lipid variables South African Journal of Animal Sciences Vol. 35 (2) 2005: pp.109-116

Effects of ursodeoxycholic acid and/or low-calorie diet on steatohepatitis in rats with obesity and hyperlipidemia.

To evaluate the effects of ursodeoxycholic acid (UDCA) and/or low-calorie diet (LCD) on a rat model of nonalcoholic steatohepatitis (NASH). Fifty-five Sprague-Dawley rats were divided into five groups. The control group (n = 9) was fed with standard rat diet for 12 wk, NASH group (n = 10) was fed with high-fat diet consisted of normal diet, 10% lard oil and 2% cholesterol for 12 wk, UDCA group (n = 10) was fed with high-fat diet supplemented with UDCA at a dose of 25 mg/(kg.d) in drinking water for 12 wk, LCD group (n = 10) was fed with high-fat diet for 10 wk and then LCD for 2 wk, and UDCA+LCD group (n = 15) was fed with high-fat diet for 10 wk, followed by LCD+UDCA for 2 wk. At the end of the experiment, body weight, serum biochemical index, and hepatopathologic changes were examined. Compared with the control group, rats in the NASH group had significantly increased body weight, liver weight, and serum lipid and aminotransferase levels. All rats in the NASH group developed steatohepatitis, as determined by their liver histology. Compared with the NASH group, there were no significant changes in body weight, liver weight, blood biochemical index, the degree of hepatic steatosis, and histological activity index (HAI) score in the UDCA group; however, body and liver weights were significantly decreased, and the degree of steatosis was markedly improved in rats of both the LCD group and the UDCA+LCD group, but significant improvement with regard to serum lipid variables and hepatic inflammatory changes were seen only in rats of the UDCA+LCD group, and not in the LCD group. LCD might play a role in the treatment of obesity and hepatic steatosis in rats, but it exerts no significant effect on both serum lipid disorders and hepatic inflammatory changes. UDCA may enhance the therapeutic effects of LCD on steatohepatitis accompanied by obesity and hyperlipidemia. However, UDCA alone is not effective in the prevention of steatohepatitis induced by high-fat diet.

The nutritional status of asymptomatic HIV-infected Africans: directions for dietary intervention?

To compare the relationships between food (nutrient) intakes and biochemical markers of nutritional status of asymptomatic HIV-infected with HIV-uninfected subjects, to gain more information on the appropriate diet for HIV-infected persons at an early stage of infection. Cross-sectional population-based survey. North West Province, South Africa. Two hundred and sixteen asymptomatic HIV-infected and 1550 HIV-uninfected men and women volunteers aged 15 years and older, recruited as 'apparently healthy' subjects from 37 randomly selected sites. Food and nutrient intakes, measured with a validated food-frequency questionnaire, and nutritional status indicated by anthropometric and biochemical variables, measured by a standardised methodology. The prevalence of HIV infection in the study population was 11.9%. The anthropometric indices and nutrient intakes of HIV-infected and uninfected subjects did not differ significantly, indicating that these 216 HIV-infected subjects were at an early stage of infection. Of the biochemical nutritional status variables, high-density lipoprotein cholesterol and total cholesterol, haemoglobin, albumin and triglycerides were significantly lower in infected subjects. They also had higher globulin and liver enzyme levels than uninfected subjects. In infected subjects, serum albumin correlated significantly with serum lipids, serum vitamin A, serum vitamin E, serum iron, total iron-binding capacity and haemoglobin. The significant positive correlations of the liver enzymes with serum lipids, albumin, vitamin A and iron, observed in HIV-uninfected subjects, disappeared in the infected subjects. Polyunsaturated fat intake showed significant positive correlations with the increased liver enzymes in infected subjects. A principal components analysis indicated that, in infected subjects, increased liver enzymes correlated with higher consumption of maize meal and lower consumption of meat and vegetables. This survey indicated that asymptomatic HIV-infected subjects who followed a diet rich in animal foods had smaller decreases in serum albumin, haemoglobin and lipid variables, and smaller increases in liver enzymes, than those who consumed a diet based on staple foods. This suggests that animal foods are associated with improved nutritional status in HIV-infected persons. These results should be confirmed with intervention studies before dietary recommendations for asymptomatic HIV-infected individuals can be made.