Increased frequencies of apolipoprotein ε2 and ε4 alleles in patients with ischemic heart disease

It has been demonstrated that the genetic polymorphism of apolipoprotein (apo) E is associated with atherosclerosis. Thus, in this study, we have examined the apo E allele frequencies in 109 patients with ischemic heart disease (IHD) and 576 Japanese people as controls, and we have compared these frequencies between patients with IHD and controls. The frequencies of the epsilon 2 and epsilon 4 alleles were significantly higher in patients with IHD than in the controls (epsilon 2: 8.2% vs 3.7%, epsilon 4: 17.0% vs 11.7%), whereas the frequency of the epsilon 3 allele was significantly lower in patients with IHD than in the controls (74.8% vs 84.6%). The epsilon 2-carrying patients with IHD were characterized by type III (43.8%) and IV (25.0%) hyperlipoproteinemia (HLP), whereas the epsilon 4-carrying patients with IHD were characterized by hypercholesterolemia (type IIb HLP: 42.8%, type IIa HLP: 28.6%). It is concluded that both epsilon 2 and epsilon 4 alleles are more associated with IHD than the epsilon 3 allele.     

Clinical features of type III hyperlipoproteinemia: analysis of 64 patients

Summary The clinical and biochemical characteristics of type III hyperlipoproteinemia are described in 64 patients (35 males and 29 females). Homozygosity for apolipoprotein E2, the presence of an abnormally cholesterol-rich very low density lipoprotein fraction (-VLDL) and an elevated ratio of very low density lipoprotein cholesterol to plasma triglycerides (>0.3; normal ratio about 0.2) were the basis for the diagnosis. Mean serum cholesterol and triglyceride concentrations at the first visit in the clinic were 426 ± 221 and 719 ±996 mg/dl, respectively. The mean age at diagnosis of the disorder was 49 years in males and 53 years in females. There was a high prevalence of obesity (72%), xanthomas (42%), and atherosclerosis (39%), especially peripheral vascular disease (31%). Early and correct diagnosis of this familial lipoprotein disorder seems necessary because of the prompt and beneficial response to therapeutic interventions.Abbreviations Apo apolipoprotein - BMI body mass index - CAD coronary artery disease - HDL high-density lipoproteins - HLP hyperlipoproteinemia - HMG CoA 3-hydroxy-3-methylglutaryl coenzyme A - LDL low-density lipoproteins - Lp(a) lipoprotein (a) - PVD peripheral vascular disease - TG triglycerides - VLDL very low density lipoproteins     

The influence of simvastatin alone or in combination with gemfibrozil on plasma lipids and lipoproteins in patients with type III hyperlipoproteinemia

Summary Nineteen adult patients with type III hyperlipoproteinemia (HLP) and homozygosity for apolipoprotein (apo) E2 were treated with the 3-hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitor simvastatin (20 or 40 mg per day) alone or in combination with the fibrate derivative gemfibrozil (450 mg per day) during a 30-week outpatient study. With the 20-mg dose (n = 19) the mean plasma cholesterol level decreased from 13.24±8.04 8.04 at baseline to 8.04±4.19 mmol/l (mean reduction 39.3%; P<0.05), and the mean plasma triglyceride level decreased from 13.47±19.22 to 7.84±7.71 mmol/l (–41.8%; NS); this was due to a decrease in very low density lipoprotein (VLDL) cholesterol from 8.95±8.64 to 4.94±4.24mmo1/l (–44.8%; NS), a decrease in low density lipoprotein (LDL) cholesterol from 3.54±0.93to 2.25 ± 0.59 mmol/l (–36.5%; P<0.01), and an increase in high density lipoprotein (HDL) cholesterol from 0.72±0.28 to 0.85±0.34 (+18.1%; NS). Thirteen patients were treated with 40 mg simvastatin per day. Under this regimen there was a further significant decrease in LDL cholesterol from 2.33±0.62 to 1.81±0.49 mmol/l (–22.3%; P<0.01). In six patients who remained hyperlipidemic on monotherapy combination drug therapy with simvastatin (40 mg per day) and gemfibrozil (450 mg per day) was given. Compared to simvastatin alone the addition of gemfibrozil further lowered plasma concentrations of total cholesterol by 14.9%, VLDL cholesterol by 23.5%, and triglycerides by 17.1%, although this was not statistically significant. No patient was discontinued from single or combination drug therapy, and no severe clinical or biochemical side effects were observed. The results of this study demonstrate the usefulness of simvastatin in the therapy of type III HLP and indicate that in individual patients who remain hyperlipidemic on monotherapy combination drug therapy with both of these drugs is effective in further reducing plasma concentrations of total cholesterol, VLDL cholesterol, and triglycerides. Although no patient in this investigation developed myopathy or rhabdomyolysis, combined fibrate-HMG CoA reductase inhibitor treatment should be considered only for severe forms of hyperlipidemia and for patients who do not respond sufficiently to mon-therapy of any of these drugs.Abbreviations Apo Apolipoprotein - CPK creatine phosphokinase - GGT gamma-glutamyl transpeptidase - HDL high density lipoproteins - HLP hyperlipoproteinemia - HMG CoA 3-hydroxy-3-methyl glutaryl coenzyme A - IDL intermediate density lipoproteins - LDL low density lipoproteins - TG triglycerides - VLDL very low density lipoproteins     

Screening for the apolipoprotein B-100 arginine3500→ glutamine mutation in patients with type III hyperlipoproteinemia

Forty-three patients with clinically and biochemically unequivocally defined type III hyperlipoproteinemia (HLP) were screened for the presence of the apolipoprotein (apo) B-100 arginine3500-->glutamine mutation. This receptor-binding defective apolipoprotein B variant is the cause of familial defective apo B-100 (FDB), an autosomal dominantly inherited disease, which leads to increased plasma cholesterol levels and premature atherosclerosis. Neither patient expressed FDB. It is concluded that the gene defect responsible for FDB is not involved in the pathogenesis of type III HLP.     

Expression of type III hyperlipoproteinemia in patients homozygous for apolipoprotein E-2 is modulated by lipoprotein lipase and postprandial hyperinsulinemia

 Type III hyperlipoproteinemia (HLP) is a multifactorial disorder associated with homozygosity for the apolipoprotein (apo) E-2 allele. Factors which may promote the development of HLP include lipoprotein lipase (LPL) and hyperinsulinemia. These factors were investigated in eight patients with type III HLP and in nine normolipidemic controls. In vitro the interaction of apoE with LPL was analyzed in cell binding assays. All type III HLP patients showed delayed triglyceride (TG) clearance and remnant lipoprotein accumulation in an oral fat tolerance test. Normolipidemic apoE-2/2 controls revealed normal TG clearance comparable to apoE3/3 controls. HLP patients showed lower LPL activity and mass than controls. Analysis of the LPL gene revealed an Asn 291→Ser mutation in three patients and a –93 T-G substitution combined with an Asp 9→Asn mutation in one control subject. In addition to LPL abnormalities, postprandial hyperinsulinemia was observed in five out of eight patients. In vitro LPL compensated the defective function of apoE-2 in mediating remnant lipoprotein binding to cells. In summary, seven out of eight patients with type III HLP showed LPL abnormalities and/or postprandial hyperinsulinemia. Together with the in vitro data these findings support a coordinate effect of apoE and LPL for the manifestation of type III HLP. Hyperinsulinemia appears to be an additional factor important for disease expression. Received: 26 June 1997 / Accepted: 10 November 1997     

Polymorphisms in the apolipoprotein A5 (APOA5) gene and type III hyperlipidemia

The great majority of patients with type III hyperlipidemia (type III HLP) are homozygous for the epsilon2 allele of the APOE gene. However, only about 10% of epsilon2 homozygotes develop type III HLP, and it has been proposed that additional genetic factors are required for the development of the condition. The frequency of two polymorphisms in the APOA5 gene, -1131T>C and S19W, has been determined in 72 hyperlipidemic patients with APOE2/2 genotype attending a lipid clinic. The frequency of both polymorphisms was significantly higher in APOE2/2 patients than in the normal population. Fifty-three percent of APOE2/2 patients were carriers of one of the polymorphisms compared to 19.7% of controls. Thus, genetic variation in the APOA5 gene is an important cofactor in the development of type III HLP.     

Response to therapy of a type III hyperlipoproteinemic subject with the rare apolipoprotein E1 (Gly127 → Asp,Arg158 → Cys) variant

Summary In a preceding paper, we described the molecular biological defects in a patient with a severe form of the familial lipoprotein disorder type III hyperlipoproteinemia (HLP) and an unusual apolipoprotein (apo) El phenotype and 1/null genotype. The index case was a 60-year-old white male of German ancestry who suffered from a myocardial infarction at age 50 years. He had distinctly elevated levels of plasma lipids (triglycerides 551 mg/dl and cholesterol 747 mg/dl, respectively) and typical clinical signs of this inborn error of lipoprotein metabolism. His mutant apo E1 was shown to be identical to a rare (already described) apo E1 (Gly₁₂₇Asp, Arg₁₅₈Cys) variant. A second independent defect at the molecular level was a nucleotide deletion of a guanosine (G) in the codon for amino acid 31 of the proband's apo 3 allele. This single base deletion (not described before) changed his apo 3 allele to a nonfunctional null allele devoid of a stable gene product. Here we describe the response to combined dietary and medical treatment of the patient with this unusual form of type III HLP. His response to therapy was excellent, similar to patients with classical type III HLP and homozygosity for apo E2. However, the correct diagnosis of this familial lipoprotein disorder seems to be necessary, even in patients without the expected apo E2/2 phenotype, in terms of the prompt and beneficial response to therapeutic interventions.Abbreviations Apo Apolipoprotein - Chol cholesterol - HDL high density lipoproteins - HDL-C HDL-cholesterol - HLP hyperlipoproteinemia - IDL intermediate density lipoproteins - IEF isoelectric focusing - LDL low density lipoproteins - LDL-C LDL-cholesterol - TG triglycerides - VLDL very low density lipoproteins - VLDL-C VLDL-cholesterol Dedicated to Prof. Dr. G. Schettler on the occasion of his 75th birthday on April 13, 1992     

Apolipoprotein E alleles and hyperlipoproteinemia in Japan

Genetic polymorphism of apolipoprotein (apo) E has been demonstrated to be associated with hyperlipoproteinemia (HLP). There are few reports on this association in Japan. Thus, in this study, we have examined the apo E allele frequencies in normolipidemia (n = 129), non-familial hypercholesterolemic (FH) type IIa HLP (n = 40), non-FH type IIb HLP (n = 35), type III HLP (n = 17), type IV HLP (n = 59), type V HLP (n = 19) and heterozygous FH (n = 51) in Japan, and compared these frequencies between normolipidemia, and different types of HLP and FH. The frequency of the epsilon 4 allele was significantly higher in type IIa (18.7%), IIb (21.4%) and V (29.0%) HLP and FH (16.6%) than in normolipidemia (8.9%), whereas the frequency of the epsilon 2 allele was significantly higher in type III (70.6%) and IV (11.0%) HLP than in normolipidemia (3.1%). These results indicate that the epsilon 4 allele is associated with non-FH hypercholesterolemia (type IIa and IIb HLP), type V HLP and FH, whereas the epsilon 2 allele is associated not only with type III HLP but also with type IV HLP.     

Atypical type III hyperlipoproteinemia in a patient with Ig A myelomatosis

Summary We studied a 58-year-old woman with severe therapy-refractory hyperlipidemia, xanthomatosis, and multiple myeloma (immunoglobulin A, lambda light chain). The lipid disorder became evident about half a year prior to the expression of myelomatosis. Clinical symptoms were similar to those found in classical type III hyperlipoproteinemia but the underlying metabolic defect was different from the one described in this primary dyslipoproteinemia. The patient has the heterozygous apolipoprotein E3/2 phenotype and her VLDL-cholesterol/serum-triglyceride ratio is unusually low at 0.05. Evidence is given that the hyperlipoproteinemia is due to an impaired catabolism of intermediate density lipoproteins probably because of a reduced hepatic triglyceride lipase activity.Abbreviations AIH autoimmune hyperlipidemia - Chol cholesterol - HDL high density lipoproteins - HLP hyperlipoproteinemia - HTGL hepatic triglyceride lipase - IDL intermediate density lipoproteins - IEF isoelectric focusing - Ig immunoglobulin - LDL low density lipoproteins - LPL lipoprotein lipase - PL phospholipids - TG triglycerides - VLDL very low density lipoproteins     

Treatment of coronary heart disease by diet and exercise: Fasting and diurnal lipoproteins

Summary The effects of a combined exercise and low-fat dientary regimen were studied in 11 patients with angiographically documented coronary heart disease (cholesterol 233 mg/dl, triglycerides 158 mg/dl) and 13 comparable patients (cholesterol 224 mg/dl, triglycerides 174 mg/dl) on usual care. During one year, fasting serum lipoproteins were lowered to ideal levels in the intervention group (cholesterol 191 mg/dl, triglycerides 100 mg/dl, LDL-cholesterol 121 mg/dl). There was no change of triglycerides and cholesterol on usual care while LDL-cholesterol rose significantly. Neither regimen had any effect on HDL-cholesterol. Diurnal triglycerides as a presumptive measure of IDL in the intervention group were diminished by 39%. The study demonstrates the feasibility of a diet and exercise regimen to normalize midly elevated plasma lipid levels and thus to possibly affect the course of coronary heart disease without drugs.Abbreviations Chol cholesterol - TG triglycerides - HDL high density lipoproteins - LDL low density lipoproteins - LP(a) lipoprotein (a) - P/S polyunsaturated to saturated fatty acid ratio - Int. Intervention group - C Control group Supported by Bundesministerium für Forschung und Technologie     

Oxidative Stress in Atherosclerosis and Diabetes

We measured the content of lipid peroxides in plasma LDL from patients with chronic CHD not accompanied by hypercholesterolemia; CHD and hypercholesterolemia; type 2 diabetes mellitus and decompensation of carbohydrate metabolism; and CHD, circulatory insufficiency, and type 2 diabetes mellitus (without hypercholesterolemia). The content of lipid peroxides in LDL isolated from blood plasma by differential ultracentrifugation in a density gradient was estimated by a highly specific method with modifications (reagent Fe²⁺ xylene orange and triphenylphosphine as a reducing agent for organic peroxides). The content of lipid peroxides in LDL from patients was much higher than in controls (patients without coronary heart disease and diabetes). Hypercholesterolemia and diabetes can be considered as factors promoting LDL oxidation in vivo. Our results suggest that stimulation of lipid peroxidation in low-density lipoproteins during hypercholesterolemia and diabetes is associated with strong autooxidation of cholesterol and glucose during oxidative and carbonyl (aldehyde) stress, respectively. These data illustrate a possible mechanism of the progression of atherosclerosis in patients with diabetes mellitus. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 7, pp. 48–51, July, 2005     

Apo E 2 phenotypes in type II diabetics with and without insulin therapy

Summary In 106 type II diabetics with persisting hyperlipidemia (i.e persistently increased triglycerides >200 mg/dl during intensive diabetes therapy) the Apo E polymorphism was examined in relation to IDDM (n=68) and NIDDM (n=38). It was shown that Apo E2 phenotypes are more (22.6% vs. 14.5%,p<0.05) and Apo E3 phenotypes less frequent in type II diabetics than in non-diabetic controls (86.8% vs. 94.7%,p<0.001). Looking at the increase in Apo E2 phenotypes it could be proved that the phenotype composition was distinctly different between diabetics with and in those without insulin therapy. While in NIDDM the increase was consequent to a higher concentration of Apo E2 homozygotes (p<0.005) it was caused by Apo E2 heterozygotes in IDDM (p<0.025) accompanied by a simultaneous decrease in Apo E3 homozygotes (p<0.025). Regarding blood lipids there was an increase in total cholesterol due only to VLDL cholesterol in IDDM as well as in NIDDM. It is concluded that in spite of similar hyperlipidemias in type II diabetics the increase in Apo E2 phenotypes is different; it is induced by heterozygotes in IDDM and by homozygotes in NIDDM.Abbreviations PVD peripheral vascular disease - CHD coronary heart disease - IDDM insulin dependent diabetes mellitus - NIDDM non insulin dependent diabetes mellitus - VLDL very low density lipoproteins - LDL low density lipoproteins - HDL high density lipoproteins     

肝脂酶基因启动子-250G/A多态性与2型糖尿病合并冠心病易感性的相关研究

目的 探讨汉族人群肝脂酶(hepatic lipase,HL)基因启动子-250G/A多态性与2型糖尿病(type 2 diabetes mellitus,T2DM)合并冠心病(coronary heart disease,CHD)的相关性.方法 采用聚合酶链反应-限制性片段长度多态性方法(polymerase chain reaction-restricted fragment length polymorphism,PCR-RFLP)检测364例T2DM+CHD组、357例T2DM组患者和356名健康对照者HL基因启动子-250G/A多态性,并分析其对脂类的影响.结果 T2DM组与对照组HL基因启动子-250G/A多态性基因型和等位基因频率差异无统计学意义(P>0.05);T2DM+CHD组GA+AA基因型频率低于对照组(0.431 vs 0.618,P=0.031);等位基因频率差异无统计学意义(P>0.05).调整混杂因素后,Spearman相关及线性回归分析,糖尿病患者(T2DM组和T2DM+CHD组),A等位基因与高密度脂蛋白胆固醇、载脂蛋白A1呈正相关;Logistic回归分析显示,A等位基因是冠心病发生的一个危险因素.结论 HL基因启动子-250G/A多态性与2型糖尿病合并冠心病的发生有关,并影响脂类代谢.     

Reciprocal effects of apolipoprotein E alleles (ε2 AND ε4) on plasma lipid levels in normolipidemic subjects

A significantly lower frequency of the epsilon 2 allele and a significantly higher frequency of the epsilon 3 allele were found in the normolipidemic Japanese population than those in the normolipidemic Caucasian populations. We have compared plasma lipid variables among the apolipoprotein (apo) E phenotype groups and estimated the average effects of the three common alleles (epsilon 2, epsilon 3 and epsilon 4) on plasma lipid levels in normolipidemic subjects. Plasma triglyceride (TG), very low density lipoprotein (VLDL)-TG, VLDL-cholesterol (C) and apo E levels were high in the apo E3/2 group, intermediate in the apo E3/3 group and low in the apo E4/3 group, whereas plasma total cholesterol (TC), low density lipoprotein (LDL)-C and high density lipoprotein (HDL)-C levels were low in the apo E3/2 group, intermediate in the apo E3/3 group and high in the apo E4/3 group. Furthermore, the epsilon 2 allele had an effect to increase the TG, VLDL-TG, VLDL-C and apo E levels and decrease the TC, LDL-C and HDL-C levels, whereas the epsilon 4 allele had an effect opposite to the epsilon 2 allele. These results indicate that the epsilon 2 and epsilon 4 alleles have the reciprocal effects on plasma lipid, lipoprotein and apo E levels.     

A common truncation variant of lipoprotein lipase (Ser447X) confers protection against coronary heart disease: the Framingham Offspring Study

Genetic variation at the lipoprotein lipase (LPL) locus has been shown to influence plasma lipids and to modulate risk of coronary heart disease (CHD). Recently, we found that the most frequent variant at this locus, involving a C-terminal truncation of two amino acids (Ser447X), was associated with both higher LPL activity and high density lipoprotein cholesterol (HDL-C) in patients with CHD. However, the impact of this S447X variant on lipids and CHD in the general population was hitherto unknown. We, therefore, analyzed a total of 1114 men and 1144 women randomly ascertained from the Framingham Offspring Study (FOS) for the presence of this LPL variant. Carrier frequency of the S447X allele was 17%, and in men carrier status was associated with higher total cholesterol (delta = 6.2 mg/dl, p = 0.03). higher HDL-C (delta = 2.3 mg/dl, p = 0.01), and lower triglyceride (TG) levels (delta = -19.4 mg/dl, p = 0.02). Moreover, in men, the S447X allele conferred significant protection against CHD (odds ratio: 0.43; p = 0.04). These effects on lipids and CHD were not seen in women. Our study represents the first report on the impact of this mutation on CHD in men from the general population, and we conclude, therefore, that the S447X variant may confer significant protection against high TG levels, low HDL-C, and premature CHD in these subjects.     

2型糖尿病血管紧张素转换酶基因与隐性心肌缺血的关系

目的　为了探讨2型糖尿病(diabetes mellitus,DM)患者血管紧张素转换酶(angiotensinconverting enzyme,ACE)基因与运动诱发的隐性心肌缺血(exercise- induced silent myocardial ischemia,SI)的关系。方法　选择静息心电图正常的2型DM患者10 8例和5 0名健康人。采用踏车运动试验进行筛选SI。应用PCR技术检测ACE基因。结果　(1)对照组及2型DM组ACE基因型及等位基因频率分布相似(P>0 .0 5 )。与非SI组比较,SI组ACE D等位基因频率明显增高(χ2 =4 .5 0 1,P<0 .0 5 ) ,两组ACE基因型频率分布相似(P>0 .0 5 )。(2 ) 2型DM患者不同ACE基因型组间临床特征及血脂水平相似(P>0 .0 5 )。(3) 2型DM患者DD型SI发生率为6 8.2 % ,明显高于II基因型组的39.5 % (χ2 =4 .5 93,P<0 .0 5 )。结论　ACE D等位基因增高2型DM患者并发SI的危险性。     

血糖控制对2型糖尿病患者载脂蛋白A水平的影响

目的 观察分析2型糖尿病患者载脂蛋白A（apoA）水平变化与血糖控制状态关系及其可能的影响机制。方法 采用自动生化仪检测213名2型糖尿病患者血浆总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）、极低密度脂蛋白（VLDL）、低密度脂蛋白（LDL）、载脂蛋白A（apoA）、载脂蛋白B（apoB），用离子交换高效液相色谱分析法测定糖化血红蛋白（HbAlc），比较其与血脂指标的相关性。结果 两组HDL-C水平差异无统计学意义[（1．26±0．45）mmol／L vs （1．13±0．35）mmol／L，P〉0．05]；控制满意组apoA水平显著高于非满意组[（1．16±0．31）g／L vs （0．98±0．32）g／L，P〈0．01]，apoB／apoA显著低于非满意组（P〈0．05）。TC、TG、LDL、VLDL水平两组差异无统计学意义（P〉0．05）。直线相关分析显示apoA与HbAlc、FBG呈显著负相关（r=-0．30，P〈0．01；r=-0．24，P〈0．01）：apoA与HDL、TC呈显著正相关（r=0．74，P〈0．01；r=0．39，P〈0．01）。结论 2型糖尿病患者血糖控制状态显著影响apoA水平，这可能是HDL功能紊乱的重要原因。     

Metabolic syndrome and small dense LDL-cholesterol

Recently, small dense low-density lipoprotein (sd-LDL) has been highlighted as a new risk factor for CHD. Sd-LDL is also closely associated with insulin resistance and hypertriglyceridemia, suggesting a high prevalence of these atherogenic particles in metabolic syndrome. It has been proposed that increased triglyceride (TG) production in the liver due to insulin resistance preferentially produces TG-rich very-low density lipoproteins (VLDL1), which finally generate sd-LDL particles. Sd-LDL is usually measured by electrophoresis or ultracentrifugation, but these methods are too laborious for general clinical use. Recently, we established a simple method for the quantification of sd-LDL-cholesterol (C) using heparin-magnesium precipitation with a filter, which selectively detects cholesterol in the denser LDL fraction with a density(d) =1.044-1.063g/ml. Patients with coronary heart disease (CHD) had substantially increased sd LDL-C levels, while their LDL-C levels were comparable to those of controls. Sd-LDL-C levels were positively correlated with TG, LDL C, and apolipoprotein B, and were inversely with HDL-C. Sd-LDL-C levels were also correlated positively with waist circumference, blood pressure, and insulin resistance index, and negatively with adiponectin level. Patients with type 2 diabetes and metabolic syndrome had substantially increased sd-LDL-C level. These results suggest that measurement of sdLDL-C is useful to evaluate overall atherogenic risks associated with metabolic syndrome and may be applicable to routine clinical examination.     

Polymorphisms at the SRBI locus are associated with lipoprotein levels in subjects with heterozygous familial hypercholesterolemia

Scavenger receptor, class B, type 1 (SRBI) is a promising candidate gene involved in the pathophysiology of atherosclerosis. We have examined the association of three common polymorphisms at the SRBI locus in 77 subjects who were heterozygous for familial hypercholesterolemia (FH). The alleles represented by polymorphisms in exon 1 and exon 8 were associated with variation in plasma concentrations of fasting triglyceride (TG). Mean plasma TG concentrations for homozygotes for the most common allele, and for heterozygotes and homozygotes for the less common allele were 85 +/- 6, 111 +/- 9 and 135 +/- 22 mg/dl (p = 0.011) for exon 1, and 96 +/- 11, 86 +/- 6 and 134 +/- 13 mg/dl (p = 0.007) for exon 8, after adjustment for age, sex and body mass index. In addition, the exon 8 polymorphism was associated with increased total cholesterol (320 +/- 15, 340 +/- 8 and 388 +/- 18 mg/dl, p = 0.015), very low density lipoprotein (VLDL) cholesterol (18 +/- 2.9, 15.7 +/- 1.6 and 33.4 +/- 3.9 mg/dl, p < 0.001) and low density lipoprotein (LDL) cholesterol (251 +/- 15, 270 +/- 8 and 312 +/- 10 mg/dl, p = 0.041) concentrations. In agreement with animal studies, our data also suggest a role for the SRBI in the metabolism of apolipoprotein B (apoB)-containing lipoproteins in humans. This pathway may constitute a backup mechanism to LDL receptor-mediated pathways for the catabolism of these lipoproteins, which could be particularly relevant in subjects with high levels of apoB-containing lipoproteins, such as those occurring in patients with FH.     

2型糖尿病合并甲状腺功能减退的影响因素分析研究

目的：探究2型糖尿病(type 2 diabetes mellitus,T2DM)合并甲状腺功能减退的影响因素。方法：选择2013年1月至2015年6月在我院接受治疗的2型糖尿病患者784例。将2型糖尿病合并甲状腺功能减退的71例患者作为甲减组,甲状腺功能正常的713例患者作为T2DM组。比较甲减组和T2DM组患者的临床资料,用单因素分析和Logistic回归分析其影响因素。结果：2型糖尿病合并甲状腺功能减退的发病率为9.06%,其中临床甲减16例,为2.04%,亚临床甲减55例,为7.02%。比较甲减组与T2DM组患者的一般临床资料,发现2型糖尿病合并甲状腺功能减退与年龄、糖尿病病程、ABI、FCP、E/A、TC、TG、LDL-C、Lp(a)、S-CRP、UAER、TPO-Ab、性别、吸烟、冠心病、DN、DNP、DR、DF、PAD、DM治疗方式有关(P<0.05)。将2型糖尿病患者是否合并甲状腺功能减退作为因变量,将上述因素纳入Logistic多元回归分析,结果显示年龄、吸烟、胰岛素治疗、TPO-Ab是2型糖尿病患者合并甲状腺功能减退的独立危险因素。结论：年龄、吸烟、胰岛素治疗、TPO-Ab是2型糖尿病患者合并甲状腺功能减退的独立危险因素,2型糖尿病患者应定期进行甲状腺功能检查,以便及早诊断和干预甲状腺功能减退。