Severe coronary disease in an adult considered at low cardiovascular disease risk with a healthy lifestyle

Lipoprotein(a) [Lp(a)] is a lipoprotein subclass well-known among the lipid community to accelerate atherosclerosis and promote thrombosis through incompletely understood mechanism. We report a case of a young man with a healthy lifestyle and no major coronary or vascular risk factors who presented to the emergency department with an acute coronary syndrome and was ultimately found to have severe coronary artery disease. A diagnostic workup revealed elevated Lp(a). He was treated with consequent reduction in Lp(a) concentration. This case highlights the need to better understand atypical lipoproteins, how they relate to cardiovascular disease, the implications for screening family members, and the need to standardize patient management guidelines for the purpose of mortality risk reduction.     

Association between apolipoprotein E polymorphism and serum lipid and apolipoprotein levels with Alzheimer's disease

We have recently demonstrated that apolipoprotein E (APOE)-varepsilon4 allele is a risk factor for Alzheimer disease (AD) in Tehran, Iran. The current study specifically aimed to examine whether APOE polymorphism in association with serum lipids-apolipoprotein level is a risk factor for AD in a population from Tehran, Iran. APOE polymorphism and plasma lipids, apoA1, apoB and lipoprotein (a) (Lp(a)) levels were determined in 94 AD patients and 111matched controls. Our study demonstrated a significant association between APOE polymorphism and the level of plasma lipids and apolipoprotein with AD in this population. The AD subjects had significantly lower apoA1 (p<0.001) and HDL-C (p<0.01) and higher apoB (p=0.01) and LDL-C (p=0.02) levels than that of the control group. The AD subjects carrying APOE-varepsilon4 allele had lower plasma apoA1 (t=5.2, p<0.002) and HDL-C level (t=2.7, p=0.01) but had higher plasma apoB (t=-5.4, p<0.002), LDL-C (t=-4.6, p=0.005) and total cholesterol (TC) (t=-2.7, p=0.01) than that of the non APOE-varepsilon4 carriers. These results indicated that AD patients with APOE-varepsilon4 allele has a distinct plasma lipid profile and carrier of this allele with low levels of apoA1 and HDL-C may be more susceptible to AD.     

Hypertriglyceridemia associated with amino acid variation Asn985Tyr of the RP1 gene

Factors predisposing to the phenotypic features of hypertriglyceridemia have not been clearly defined. Here we report an association between a missense coding region polymorphism Asn985Tyr in the retinitis pigmentosa 1 gene (RP1) and plasma triglyceride (TG) levels in 332 adult individuals from an east-central area of Japan. Age and gender-adjusted levels of LDL-cholesterol, TG, and HDL-cholesterol were analyzed. When we separate the subjects into two genotypic groups regarding this amino acid variation, those who lack the 985-Asn allele (asparagine at residue 985) had significantly higher plasma TG levels than the others who had at least one 985-Asn allele (mean: 175.8 mg/dl vs 123.3 mg/dl; P=0.0006, Mann-Whitney test). Similarly, the former subjects had significantly lower HDL-cholesterol levels than the latter (mean: 48.0 mg/dl vs 53.8 mg/dl; P=0.038). Of the 280 individuals without a 985-Asn allele, approximately half of the individuals presented with hypertriglyceridemia, whereas only a quarter were hypertriglyceridemic among 52 individuals with the 985-Asn allele (P=0.04). Although this SNP marker may itself be in linkage disequilibrium with other unexamined functional variants within this locus, our data suggest that genetic variation at the RP1 locus is one of the likely candidate determinants for plasma triglyceride and HDL-cholesterol metabolisms.     

Effects of apoE gene polymorphism on Lp(a) concentrations depend on the size of apo(a): a study of 466 white men

 Polymorphisms in the genes for the low-density lipoprotein (LDL) receptor ligands, apolipoprotein E (apoE), and apolipoprotein B (apoB) are associated with variation in plasma levels of LDL cholesterol. Lp(a) lipoprotein(a) [Lp(a)] is LDL in which apoB is attached to a glycoprotein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined isoforms differing in molecular weight, which are inversely correlated with Lp(a) concentrations in blood. The interaction of apo(a) with triglyceride-rich lipoproteins differs with the size of apo(a), and therefore the effects of apoE gene polymorphism on Lp(a) levels could also depend on apo(a) size. We have investigated the possible effect of genetic variation in the apoE and apoB genes on plasma Lp(a) concentrations in 466 white men with different apo(a) phenotypes. Overall there was no significant association between the common apoE polymorphism and Lp(a), but in the subgroup with apo(a)-S4, concentrations of Lp(a) differed significantly among the apoE genotypes (P=0.05). Lp(a) was highest in the apoE genotypes ɛ₂ɛ₃ and ɛ₃ɛ₃ and lowest in genotype ɛ₃ɛ₄, and the apoE polymorphism was estimated to account for about 2.4% of the variation in Lp(a). In contrast, in the subgroup with apo(a)-S2 Lp(a) was significantly lower (P=0.04) in apoE genotype ɛ₂ɛ₃ than in genotype ɛ₃ɛ₃. Lp(a) concentrations did not differ among the XbaI (P=0.65) or SP 24/27 (P=0.26) polymorphisms of the apoB gene. The expected effects of both apoE and apoB polymorphism on LDL levels were significant in the whole population sample and in subjects with large-sized apo(a) isoforms (P<0.01), whereas no effect was seen in those with low molecular weight apo(a) isoforms. We conclude that the influence of apoE genotypes on Lp(a) concentrations depends on the size of the apo(a) molecule in Lp(a), possibly because both apo(a)-S4 and apoE4 have high affinity for triglyceride-rich lipoproteins and may be taken up and degraded rapidly by remnant receptors. Received: 12 January 1995 / Accepted: 12 July 1996     

Interaction between low density lipoprotein receptor (LDLR) and apolipoprotein E (apoE) alleles contributes to normal variation in lipid level

Subjects drawn from a population-based register were studied with respect to lipid level association. The association of isoforms of apolipoprotein E (apoE) with lipid level in the general population was found to be limited to people with one particular genotype at the low density lipoprotein receptor (LDLR) locus. The results presented in this paper suggest that functional LDLR variants enhance or limit the effect of isoforms of apoE. The association between apoE4 and serum total and LDL cholesterol level may be mediated through the LDL (apoB100, apoE) receptor to a greater extent than previously thought.     

A promoter SNP (-1323T>C) in G-substrate gene (GSBS) correlates with hypercholesterolemia

Factors predisposing to the phenotypic features of higher total cholesterol (TC) have not been clearly defined. Here we report an association between a promoter SNP (–1323T>C) in G-substrate gene (GSBS) and TC levels in 368 adult individuals from an east-central area of Japan. Age and gender-adjusted levels of LDL-cholesterol, TG, TC, and HDL-cholesterol were analyzed. When we separate the subjects into two genotypic groups regarding T allele, those who bear the T allele had significantly higher plasma TC levels than the others who lack the T allele (mean; 239.6 mg/dl vs. 210.6 mg/dl; p=0.003; Mann–Whitney test). Of the 341 individuals with the T allele, approximately 80% individuals presented with hypercholesterolemia, whereas only 44% were hypercholesterolemic among the 27 individuals without the T allele (p=0.0001). These results indicate a significant elevating effect of plasma TC levels by a SNP in the putative regulatory region of the G-substrate gene in our studied population. These data suggest that genetic variation at the G-substrate gene may be one of the determinants for plasma lipoprotein levels.     

MK2、ZFP36基因变异与新疆维吾尔族人群高密度脂蛋白胆固醇水平的相关性

目的 探讨MK2及ZFP36基因功能区多态位点与新疆和田地区维吾尔族人高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)的相关性.方法 应用整群随机抽样方法抽取930名维吾尔族人外周静脉血,检测其血脂水平以及肿瘤坏死因子-α,并在维吾尔族血脂异常人群中测序筛查MK2及ZFP36基因功能区的变异位点,选取代表性位点,应用TaqMan-PCR在大样本人群中进行基因型鉴定及病例-对照关联研究.结果 (1)年龄小于50岁维吾尔族男性MK2基因rs45514798多态与HDLC可能相关(P=0.054,控制年龄、吸烟、饮酒、腹围、腰臀比、体重指数、肿瘤坏死因子-α之后OR为0.261,95％CI为0.082～0.833).(2) MK2基因rs45514798显性模型在小于50岁男性的不同基因型间总胆固醇、HDL-C水平、低密度脂蛋白胆固醇水平的差异具有统计学意义(P均＜0.05).小于50岁女性中rs45514798显性模型基因型间总胆固醇、低密度脂蛋白胆固醇差异具有统计学意义(P＜0.05).(3)ZFP36基因多态性的基因型在低HDL-C组和对照组分布比较差异无统计学意义.结论 MK2基因rs45514798位点可能与年龄小于50岁的新疆维吾尔族男性HDL-C相关,ZFP36基因与新疆维吾尔族人群HDL-C不相关.     

卵磷脂胆固醇酰基转移酶基因单核苷酸多态性与冠心病脂代谢易感性的关联研究

目的：检测卵磷脂胆固醇酰基转移酶（lecithin cholesterol acyltransferase,LCAT）基因3个编码区单核苷酸多态位点在中国人群中的分布频率，并初步探讨它们与脂代谢和冠状动脉粥样硬化性心脏病（coronary atherosclerotic heart disease,CHD）易感性的关系。方法：采用聚合酶链反应－限制性片段长度多态性方法，分析209名正常人和203例CHD患者中608C／T、911T／C和1188C／T（参照序列：NM_000229）3个位点的多态性。结果：608C和608T等位基因频率分布符合Hardy-Weinberg平衡。CHD患者组608T频率显著低于正常人群（P＝0．034）。与无608T CHD患者相比，具有608T的CHD患者的血浆高密度脂蛋白胆固醇显著升高（P＝0．015）。911T／C和1188C/T在两组中均未检出。结论：LCAT基因608T等位基因与CHD患者较高的血浆高密度脂蛋白胆固醇水平相关联，可能与中国人CHD相关。911T／C和1188C／T在中国人群中非常罕见。     

Association of interleukin-17A and -17F gene single-nucleotide polymorphisms with autoimmune thyroid diseases

Th17 lymphocyte and its relative cytokines have been shown to play an important role in autoimmune thyroid diseases (AITD). The aim of this study was to investigate the association between IL-17A and IL-17F gene polymorphisms and two main types of AITD, Graves' disease (GD) and Hashimoto's thyroiditis (HT). Whole blood specimens and clinical data were collected from 508 AITD patients (326 with GD and 182 with HT) and 224 age- and gender-matched healthy controls, respectively. IL-17A (rs2275913, rs8193037, rs3819025) polymorphism was determined using DNA sequencing method and IL-17F/rs763780 polymorphism was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR -RFLP). The results indicated that the frequencies of IL-17F/rs763780 genotypes in patients with GD and HT differed significantly from their controls (P = 0.013 and P = 0.005, respectively); the G allele frequencies were also significantly higher in the patient groups than the control groups (P = 0.002 and 0.001, respectively). For IL-17A/rs2275913 and rs8193037 SNP, no significant difference was observed in patients with either GD or HT compared to the control groups (P>0.05). Interestingly, for rs3819025, the frequency of A allele was lower in patients with GD than controls (P = 0.011). The frequencies of haplotype AGGG and GGGG in patients with GD and HT were significantly higher than in controls (P = 0.012, P = 0.019, P = 0.017 and P = 0.029, respectively). In conclusion, the results indicate that IL-17F/rs763780 polymorphisms may affect the susceptibility to AITD, and IL-17A/rs3819025 SNP is likely a protective factor to GD in the Chinese population.     

汉族人群脂联素基因-11377C/G多态性与子痫前期的相关性研究

目的探讨福建莆田地区汉族人群脂联素基因（APN）单核苷酸多态性（SNP）和子痫前期（pre-eclampsi-a）及其血脂水平的关联性。方法研究对象516例,包括对照组260例,子痫前期病例组256例。采用聚合酶链反应一限制性片段长度多态性（PCR-RFLP）法鉴定APN基因启动子-11377C/G单核苷酸多态性并测定血脂水平。结果 APN基因启动子-11377C/G位点G等位基因频率和GG＋CG基因型频率在子痫前期病例组明显升高,差异有统计学意义（P〈0.05）。子痫前期病例组内GG＋CG基因型患者血清甘油三酯（TG）、血浆总胆固醇（TC）和低密度脂蛋白（LDL）值均高于CC基因型（P〈0.05）。结论 APN基因启动子-11377C/G位点GG＋CG基因型与子痫前期及其血浆TG、TC和LDL水平升高关联,C-G多态性提高了子痫前期合并血脂代谢紊乱的风险性。     

The anti-inflammatory effects of statins on patients with rheumatoid arthritis: A systemic review and meta-analysis of 15 randomized controlled trials

Background

Over the past several years, numerous studies investigated the anti-inflammatory effects of statin on patients with RA. However, the findings of the individual studies were often inconsistent or conflicting.

Biochemical and immunohistochemical changes in delta-9-tetrahydrocannabinol-treated type 2 diabetic rats

The regulation of glucose, lipid metabolism and immunoreactivities of insulin and glucagon peptides by delta-9-tetrahydrocannabinol (Δ⁹-THC) in diabetes were examined in an experimental rat model. Male Sprague-Dawley rats were divided into four groups: (1) control, (2) Δ⁹-THC treated, (3) diabetic, and (4) diabetic + Δ⁹-THC. The type 2 diabetic rat model was established by intraperitoneal (i.p.) injection of nicotinamide (85 mg/kg body weight) followed after 15 min by i.p. injection of streptozotocin (STZ) at 65 mg/kg of body weight. Δ⁹-THC and Δ⁹-THC treated diabetic groups received 3 mg/kg/day of Δ⁹-THC for 7 days. The immunolocalization of insulin and glucagon peptides was investigated in the pancreas using a streptavidin–biotin–peroxidase technique. High density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), very low density lipoprotein cholesterol (VLDL), triglycerides (TG), total cholesterol (TC) and total protein (TP) levels were measured in serum. Total islet area percent of insulin immunoreactive cells slightly changed in diabetic + Δ⁹-THC rats compared to diabetic animals. However, the area percent of glucagon immunoreactive cells showed a decrease in diabetic + Δ⁹-THC rats compared to that of diabetic animals alone. Serum TC, HDL and LDL levels of diabetes + Δ⁹-THC group showed a decrease compared to the diabetic group. These results indicate that Δ⁹-THC may serve a protective role against hyperlipidemia and hyperglycemia in diabetic rats.     

Experimental nephrotic syndrome in the rat induced by puromycin aminonucleoside. Plasma and urinary lipoproteins

Nephrotic syndrome (ascites, proteinuria, hypoalbuminemia, and hyperlipidemia) was induced in male Wistar rats by daily administration of puromycin aminonucleoside (20 mg/Kg). Hyperlipidemia was the result of a marked increase of all plasma lipids particularly triacylglycerols (7 to 8-fold the values found in the pair fed control rats). All plasma lipoprotein fractions were increased in nephrotic rats. VLDL increased 14-fold; LDL and HDL were 7- and 6.5-fold respectively above the pairfed control values. The apoprotein pattern of nephrotic VLDL was characterized by a loss of apoC-1 peptide and the presence of two bands in the region of ARP and apoA-1 peptides. SDS polyacrylamide gel electrophoresis indicated an increased content of ARP in nephrotic VLDL. Nephrotic LDL but not control LDL contained peptides entering the running gel in 8 M-urea gels in the region of ARP, A-1 and C peptides. Nephrotic HDL were almost devoided of ARP and apoA-IV peptides whereas control HDL contained significant amounts of these peptides. The urine of nephrotic rats contained a large amount of lipids (21.9 vs 1.5 M × 10^?6/day). Fatty acids, cholesteryl esters, and phospholipids were the major lipids of nephrotic urine. More than 72% of these lipids were isolated by preparative ultracentrifugation into three fractions: Total Low Density Lipoproteins (< 1.050 g/ml), High Density Lipoproteins (1.063 to 1.210 g/ml) and Ultracentrifugal Residue (> 1.210 g/ml) which contained respectively 7.4, 44.4, and 48.2% of the total recovered lipids. Urinary excretion of HDL was much greater than that of TLDL indicating that lipoproteinuria of aminonucleoside induced nephrotic syndrome was selective. The relationship between these findings, previously reported data and the alterations of plasma and urinary lipoproteins in human nephrotic syndrome is discussed.     

SCN7A 基因单核苷酸多态性与原发性与原发性高血压的相关研究

目的　检测中国人电压调控钠通道 7型α亚单位基因 (sodium channel,voltage- gated,type ,alpha polypeptide,SCN7A)调控区和编码区的单核苷酸多态性 (single nucleotide polymorphisms,SNPs) ,并探讨其与上海汉族人群原发性高血压的关系。　方法　采用直接测序法检测基因启动子、编码区和部分内含子的序列 ,以确定中国人群中 SCN7A基因 SNPs的位置及类型。采用聚合酶链反应 -限制性片段长度多态性及直接测序法 ,对上海汉族 96例原发性高血压患者和 96名正常血压对照者进行 SNP检测和关联研究。对所发现的 P<0 .0 5的 SNP位点 ,进一步扩大样本 (病例、对照组各 2 88例 )加以验证。结果　在 13132 bp的测序长度中 ,共发现 32个 SNP,包括启动子区 7个 ,编码区 10个 (其中改变氨基酸编码的 6个 ) ,3′非编码区 1个 ,内含子区 14个 ,其中 30个为新发现的 SNP。关联研究结果显示 SNP0 2 1在病例和对照组中的分布差异存在显著性 (P <0 .0 1) ,该 SNP多态可改变氨基酸的编码序列。　结论SCN7A基因变异可能与上海汉族人群原发性高血压相关。     

Lack of correlation between serum cholesterol levels, lymphocyte plasma membrane fluidity and mitogen responsiveness in young and aged chickens

Chickens were studied in an attempt to demonstrate correlations between serum lipid levels and peripheral blood lymphocyte (PBL) plasma membrane fluidity and mitogen responsiveness: (a) in the laying hen; (b) during aging; and (c) following dietary manipulation of serum cholesterol of young and aged chickens. The membrane fluidity of PBL from laying hens was significantly greater than that of immature birds. However, no direct correlation was found between serum lipid levels, nor the serum free cholesterol/phospholipid (FC/Pl) mole composition and PBL membrane fluidity in any of the age-groups tested. Likewise, no correlation was found either between serum FC/Pl mole ratio or membrane fluidity and mitogen responsiveness of PBL from birds up to 5 years of age nor was there any evidence for a decline in mitogen responsiveness up to this age. Supplementation of diets with 1% cholesterol induced hypercholesterolemia, mainly in the very low density lipoprotein (VLDL) fraction, but membrane fluidity and mitogen responsiveness remained unaffected.     

Apolipoprotein E epsilon4 offers protection against age-related macular degeneration

Background

In many previous studies, age-related macular degeneration (ARMD) has been linked to a variety of different risk factors. The publications have debated whether apolipoprotein E (apoE) ε4 serves as a potential protective factor in the development of the disease. Other studies have classified the behavior of this protein in different pathologies, including Alzheimer’s disease (AD) and cardiovascular disease. The general behavior of the ε4 isoform of ApoE is different than the predominant ε3 isoform.

Hypothesis

We propose that the general characteristics and molecular behavior of apoE ε4 cause it to be a protective factor against the development of ARMD by preventing cumulative effects of oxidative retinal damage.

Evaluation of Hypothesis

Review of the literature related to ARMD and ApoE, using OVID as our main database, led to the development of several theories regarding ApoE ε4’s behavior compared to ε3 and potential explanation of its protective characteristics.

Consequences of Hypothesis

We relate these theories to the potential behavior of ApoE ε4 in other situations including choroidal neovascularization, Alzheimer’s Disease (AD), cardiovascular disease, herpes simplex virus infection, and smoking.

Discussion

The potential implications of this theory could be used as a branching point for further studies that examine the role of the different apoE isoforms, in relation to the other risk factors for ARMD.     

High-density lipoprotein phospholipids interfere with dendritic cell Th1 functional maturation

Lipoproteins are both lipid carriers in the blood and regulators of essential biological processes. Several studies demonstrated that lipoproteins modified during pathological conditions could alter dendritic cell (DC) maturation. Here the immune function of non-pathological lipoproteins is addressed by analysing their impact on human DC maturation triggered by TLR ligands. Upon TLR4 stimulation, low- and high-density lipoproteins (LDL and HDL) strongly inhibited the ability of DC to induce a Th1 response of T cells, characterized by high levels of IFNγ secretion, whereas the effect of very low-density lipoprotein was subject to variations. HDL also inhibited the Th1 function of DC stimulated by TLR1/2 and TLR2/6 ligands. The phospholipid fraction from HDL retained the inhibitory activity of the lipoprotein. We identified the 1-palmitoyl-2-linoleyl-phosphatidylcholine (PLPC) as one active phospholipid that inhibited the Th1 function of mature DCs whereas the dipalmitoyl-phosphatidylcholine had no significant effect. The treatment of DC by PLPC, 24 h before TLR4 stimulation, resulted in reduced activation of NF-κB. This study shows that some HDL phospholipids have a direct immunoregulatory function, by modulating DC ability to activate a Th1 response of T cells.