A 9.6 kilobase deletion in the low density lipoprotein receptor gene in Norwegian familial hypercholesterolemia subjects

Haplotype analysis of the low density lipoprotein receptor (LDLR) gene was performed in Norwegian subjects heterozygous for familial hypercholesterolemia (FH). Southern blot analysis of genomic DNA, using an exon 18 specific probe and the restriction enzyme NcoI, showed that two out of 57 unrelated FH subjects had an abnormal 3.6 kb band. Further analyses revealed that this abnormal band was due to a 9.6 kb deletion that included exons 16 and 17. The 5' deletion breakpoint was after 245 bp of intron 15, and the 3' deletion breakpoint was in exon 18 after nucleotide 3390 of cDNA. Thus, both the membrane-spanning and cytoplasmatic domains of the receptor had been deleted. A polymerase chain reaction (PCR) method was developed to identify this deletion among other Norwegian FH subjects. As a result of this screening one additional subject was found out of 124 subjects screened. Thus, three out of 181 (1.7%) unrelated Norwegian FH subject possessed this deletion. The deletion was found on the same haplotype in the three unrelated subjects, suggesting a common mutagenic event. The deletion is identical to a deletion (FH-Helsinki) that is very common among Finnish FH subjects. However, it is not yet known whether the mutations evolved separately in the two countries.     

Lipidstatus und basale Steroidhormonspiegel nach 16 Wochen Lovastatintherapie bei primärer Hypercholesterinämie

Summary We examined the effect of a 16 week therapy with the HMG CoA reductase inhibitor lovastatin in 29 patients (mean age 43 years) with primary hypercholesterolemia. All patients had cholesterol levels above 250 mg/dl (mean 348 ±96 mg/dl) inspite of a lipid lowering diet and a therapy with conventional lipid lowering drugs during a three month screening period. After 4 weeks on placebo 20 mg lovastatin was given orally for 4 weeks. If total cholesterol exceeded 200 mg/dl the dose of lovastatin was increased monthly by 20 mg up to the maximal dose of 80mg/day. After 16 weeks lipid values changed compared with the placebo period: total-cholesterol –25%, triglycerides –8.6%, LDL-cholesterol –31%, APO B –25%, HDL-cholesterol +5.8%, APO AI +0.8%, total-cholesterol/HDL-cholesterol –25%. There was a significant improvement of lipid parameters after lovastatin therapy compared with conventional lipid lowering drugs at the end of the screening period. Lovastatin was well tolerated. A small and reversible rise of transaminases and/or creatinine kinase was observed in 6 patients. Basal levels of ACTH in the morning increased significantly during lovastatin therapy within the normal range. This observation was more frequent in females (10/12) than in males (10/ 17).

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Abkürzungen HMG Co A 3-Hydroxy-3-Methyl-Glutaryl-Coenzym A - TChol Gesamtcholesterin - LDL low density lipoprotein - HDL high density lipoprotein - TG Triglyceride - APO AI/B Apolipoprotein AI/B - ACTH Adrenocorticotropes Hormon Diese Publikation enthält Ergebnisse des Dissertationsarbeit von Frau Angela Bink.     

Genetics of the low density lipoprotein receptor:

Fibroblast association (plasma membrane binding plus intracellular accumulation) and degradation of radioiodinated low density lipoprotein (125I-LDL) index plasma membrane LDL receptor activity. Cultured fibroblasts from 23 subjects affected with familial hypercholesterolemia (HC) and from 95 subjects without HC (non-HCs) were tested for 125I-LDL association and degradation. Both LDL receptor activity indices were twice as high in non-HC and HC heterozygous cell strains. This is compatible with a major gene effect on LDL receptor activity. However, a considerable overlap between non-HC and HC heterozygous values was found in the 125I-LDL association assay [median (range) 970 (330-2500), and 450 (250-490), respectively] and in the degradation assay [median (range) 810 (280-2020), and 470 (160-790), respectively]. The values are expressed as ng 125I-LDL X mg cell protein-1 X 4.5 h-1. These great overlaps in the LDL receptor activity indices support the view that the influence of LDL receptor activity on the HC phenotype may be smaller than believed previously. Furthermore, for the diagnosis of HC, these LDL receptor activity assays are far more expensive and have less sensitivity and specificity than simple serum cholesterol determination. The LDL receptor-dependent 125I-LDL association values for the HC heterozygous individuals clustered into four groups. Family data supported the hypothesis that this variation could be due to four different LDL receptor variants, each coded for by different alleles at the LDL receptor locus. If confirmed, this finding may have implications for the understanding of the variable expression of HC and also of the genetic impact on lipoprotein metabolism and susceptibility to atherosclerosis in non-HCs.     

HLA class II DPB1, DQA1, DQB1, and DRB1 genotypic associations with occupational allergic cough to Bunashimeji mushroom

We previously reported that two-third of workers in a Bunashimeji mushroom (Hypsizigus marmoreus) farm complained of respiratory allergic symptoms, but one-third workers did not suffer from such symptoms even when working for a long period. CD4+ T-helper (Th) cells increased, and Th2/Th1 ratio increased in the allergic workers. To address these immunological backgrounds, we have investigated whether there is any relationship between mushroom allergy and human leukocyte antigen (HLA) class II alleles of DPB1, DQA1, DQB1, and DRB1 by using the polymerase chain reaction-restriction fragment length polymorphism (RFLP) and sequencing-based typing methods. We observed that the allele frequencies of DQA1*0103, DQB1*0601, and DRB1*0803 were significantly higher in the workers having no allergic symptoms than allergic workers (DQA1*0103: 57 vs 25%, DQB1*0601: 49 vs 14%, and DRB1*0803: 29 vs 0%). However, this phenomenon was not seen in workers producing another kind of mushroom, Honshimeji (Lyophyllum aggregatum). The HLA-DRB1*0803 allele alone, the DRB1*0803, DQA1*0103, DQB1*0601 haplotype, or both were negatively associated with allergy to Bunashimeji, and these alleles might be involved in the prevention of Bunashimeji mushroom-specific respiratory allergy.     

阿托伐他汀与辛伐他汀治疗高脂血症的效果

目的分析在高脂血症患者治疗中应用阿托伐他汀和辛伐他汀的降脂效果。方法将2017年1月—2020年1月在我院医治的90例高脂血症患者随机设为两个组别,给予对照组(45例)辛伐他汀治疗,给予试验组(45例)阿托伐他汀治疗。观察两组患者治疗前后血脂水平和生化指标变化情况。结果试验组治疗后总胆固醇、三酰甘油、低密度脂蛋白胆固醇低于对照组,高密度脂蛋白胆固醇高于对照组,两组对比差异具有统计学意义(P<0.05)。两组患者治疗后肌酐、尿素氮指标差异无统计学意义(P>0.05)。结论阿托伐他汀和辛伐他汀应用于高脂血症患者治疗中均能起到不同程度的降脂效果,但阿托伐他汀的效果更好,安全可靠。     

血脂康对肾病综合征病人脂代谢的影响

目的 :研究血脂康对肾病综合征病人脂代谢的调节作用 ,并与辛伐他汀比较。方法 :37例肾病综合征高脂血症病人随机分为血脂康组 (19例 ,血脂康 1.2g/d)和辛伐他汀组 (18例 ,舒降之 10mg/d) ;治疗前和治疗 4周后分别检测肝、肾功能、血脂、电解质及 2 4h尿蛋白。结果 :两组在治疗 4周后TC、TG及LDL C均下降 (P均 <0 .0 1) ,TP、ALB和HDL C升高 (P <0 .0 1或 <0 .0 5 ) ;而两组间比较治疗前和治疗 4周后的上述指标差异均无显著性 (P均>0 .0 5 )。结论 :血脂康能显著性降低肾病综合征病人TC、TG和LDL C水平 ,提高HDL C水平。     

血压、血脂、血糖与心脑血管疾病相关性研究

目的 :为了解高血压、高血脂、高血糖在心脑血管疾病的发病方面所起的作用及影响程度的相关性。方法 :对武汉市 3 15 1例脑力劳动者健康体检资料进行分析。结果 :血糖、血脂均值及高血压、糖尿病、心脑血管疾病的患病率都随年龄的增长而增高 ,高血压与心脑血管疾病在患病率增高方面有明显的相关性 ,而血脂、血糖水平与心脑血管疾病的患病率之间相关性却不甚明显。结论 :脑力劳动者患高血压病 ,特别是长期药物控制不好的高血压病才是心脑血管疾病发病的最重要危险因素 ,降低心脑血管疾病的发病率和复发率的关键是 ,加强对高血压病的监控 ,合理用药 ,稳定血压     

高脂饮食诱导的高胆固醇血症对雄性Wistar大鼠肾脏的毒性作用

目的 研究高胆固醇血症对雄性Wistar大鼠肾脏的毒性作用。方法 用5%胆固醇饲料喂养雄性Wistar大鼠,制备高胆固醇动物模型,分别于实验第30、60和90d测定肾功能、24h尿蛋白、肾皮质胆固醇（Ch）及各磷脂含量,并进行病理形态及组织定量分析。结果 在实验周期内实验组（E组）大鼠血浆肌酐水平无显著变化;第90d,E组24h尿微量白蛋白、肾皮质Ch、磷脂酰胆碱（PC）及磷脂酰乙醇胺（PE）显著高于正常对照组（C组）;病理形态及组织定量分析显示肾小球系细胞增垂、炎性细胞浸润、系膜基质增多、毛细血管塌陷、上皮细胞足突融合,肾小球体积增大。IgG直接免疫荧光阴性,肾小球内无电子致密物沉积。相关分析显示肾小球体积、肾皮质Ch含量及24h尿微量白蛋白排泄率等与血浆总胆固醇（TCh）及低密度脂蛋白（LDL）浓度呈显著正相关关系。结论 饮食诱导的高胆固醇血症可导致Wistar大鼠肾毒性损伤。