ApoE和SLCO1B1基因多态性与冠心病的相关性

目的 探讨人群中ApoE、SLCO1B1 388A>G和521T>C基因多态性与冠心病的关系。方法 采用病例对照研究方法,冠心病组为确诊的冠心病患者827(男586,女241)例,平均年龄（64±12）岁;对照组为健康个体753(男530,女223)例,平均年龄（62±14）岁。通过PCR-荧光探针法对ApoE和SLCO1B1基因多态性进行检测,并统计分析基因多态性与冠心病的关系。结果 ①冠心病组携带E3/4基因型显著高于对照组（P<0.05）;携带￡4等位基因显著高于对照组（P<0.05）。 ②SLCO1B1 388A>G和521T>C的基因型和等位基因频率以及SLCO1B1基因单倍体频率在冠心病组和对照组中无统计学差异。结论 ①ApoE基因￡4等位基因频率上升是冠心病的重要标志。②SLCO1B1 388A>G和521T>C基因多态性位点与冠心病无明显的相关性。     

甘肃地区汉族ACS患者ApoE及SLCO1B1基因多态性分布研究

目的 初步了解甘肃地区汉族急性冠状动脉综合征（ACS）患者的SLCO1B1和ApoE基因型及等位基因频率分布特点,同时探讨其与血脂水平的相关性。方法 将243例于2016年11月至2017年12月期间在甘肃省人民医院心内科入住的ACS患者作为对象开展研究工作,采用聚合酶联反应对患者血样进行SLCO1B1及ApoE基因多态性分析,分析其多态性分布情况,并对空腹血脂水平进行检测。结果 本研究ACS患者血液样本中共检测到6种SLCO1B1基因型,其中以耐受较高型*1b/*1b、*1a/*1b、*1a/*1a为主,分别占比44.4%、35.4%、5.3%,耐受中等型*1a/*15、*1b/*15、*1a/*5分别占比4.5%、9.9%、0.49%,耐受较低型只检测出占比0.4%的*15/*15基因型,未检出*5/*5、*5/*15型。SLCO1B1等位基因*1b、*1a、*15占比分别为55.52%、32.13%、12.35%。受检患者血样中共检测到6种ApoE基因型,一般型E2/E4、E3/E3占比分别为0.8%、77.00%,有害型[E3/E4(14.0%)、E4/E4(1.2%)],有益...     

SLCO1B1和ApoE基因多态性对老年ASCVD患者血脂水平的影响

目的 研究老年ASCVD患者血脂水平与SLCO1B1 521T>C、ApoE 526 C>T和ApoE 388 T>C基因多态性的相关性。方法 选取2020年10月至2021年12月于重庆市永川区人民医院心内科就诊的ASCVD患者266例,至少服用阿托伐他汀3个月以上,抽取其静脉血进行SLCO1B1 521T>C、ApoE 526 C>T和ApoE 388 T>C基因检测,进行Hardy-Weinberg平衡分析及各基因型血脂水平比较。结果 SLCO1B1 521T>C、ApoE 526 C>T和ApoE388 T>C各基因型均符合Hardy-Weinberg平衡（P>0.05）;SLCO1B1基因521位点主要以TT型为主,TC+CC型血脂TC、TG、LDL-C水平均高于TT型,而HDL-C低于TT型,但两组比较均无统计学意义（P>0.05）;与ApoE基因E2型相比,E4型患者服用阿托伐他汀3个月后,LDL-C水平仍然较高,且具有统计学意义（P<0.05）。结论 阿托伐他汀的调脂疗效受到ApoE基因多态性影响,...     

甘肃地区ApoE与SLCO1B1基因多态性及基因型与血脂水平的相关性

目的 了解甘肃地区SLCO1B1和ApoE基因的分布特征及基因型对血脂水平的影响。 方法 采用横断面研究,对甘肃省人民医院心内科的386名患者采用聚合酶链反应进行基因多态性分析并检测其入院血脂水平,统计不同基因型的分布特征,探讨基因多态性与血脂水平的相关性。 结果 与血脂正常组相比较,血脂异常组年龄年轻、体质量指数（BMI）显著增大、TC、TG和LDL-C水平显著升高。SLCO1B1基因型*1b/*1b、*1a/*1b分别占比:42.5%、35.8%,其次是*1b/*15（10.9%）、*1a/*1a（5.4%）、*1a/*15（4.2%）、*15/*15（1.3%）,但未检测到*1a/*5、*5/*5、*5/*15基因型。SLCO1B1基因等位基因*1a、*1b、*15占比分别为:25.4%、65.8%、8.8%。388A > G与521T > C突变频率分别为74.6%、8.8%,正常与异常血脂水平组SLCO1B1基因型、等位基因分布差异未见统计学差异。ApoE基因型E3/E3、E3/E4分别占比:74.9%、15.5%;其次是E2/E3（6.7%）、E4/E4（1.3%）、E2/E4（1.0%）、E2/E2（0.5%）;等位基因ε2、ε3、ε4分别占比:4.4%、86.0%、9.5%;正常与异常血脂水平组ApoE基因型、等位基因分布差异未见统计学差异。单因素分析、多因素分析及Pearson相关性分析表明SLCO1B1、Apoe基因型与血脂水平无相关性。 结论 SLCO1B1、APOE基因多态性对血脂水平无相关性。      

ApoE与SLCO1B1基因多态性与老年脑梗死患者颅内动脉粥样硬化狭窄的相关性

目的 分析ApoE与SLCO1B1基因在老年脑梗死患者颅内动脉粥样硬化狭窄中的分布情况,及动脉狭窄程度与血脂的关系.方法 选取2018年2月至2019年2月北京中医药大学东方医院脑动脉粥样硬化患者200例为脑梗死组,以北美症状性颈动脉内膜剥脱术研究法分级标准划分动脉粥样硬化狭窄分级,其中无狭窄患者26例、轻度狭窄患者4...     

闽东地区SLCO1B1基因型分布及其对血脂的影响

目的：探究闽东地区人群SLCO1B1基因型的分布,结合血脂情况,研究SLCO1B1基因型对血脂水平的影响。方法：收集2020年3月至2021年2月于宁德师范学院附属宁德市医院进行SLCO1B1基因型检测的2 655例宁德籍贯患者SLCO1B1基因型及服用他汀类等降脂药前的血脂水平,采用统计学方法分析SLCO1B1与血脂水平的相关性。结果：闽东地区人群SLCO1B1*1b(388A>G)基因型分布为AA 5.80%、AG34.73%、GG 59.47%,SLCO1B1*5(521T>C)基因型分布为TT 77.25%、TC 21.21%、CC1.54%;SLCO1B1*5(521T>C)CC型的携带者,高密度脂蛋白胆固醇（HDL-C）水平显著升高（P<0.05）。结论：SLCO1B1*5(521T>C)基因型可能成为预测血脂异常的新靶点,闽东地区12.15%的人群SLCO1B1*5(521T>C)携带C等位基因,结合既往研究,服用他汀类药物需关注患者肌毒性的风险。     

一例Rotor综合征SLCO1B1和SLCO1B3基因突变分析

目的初步探讨1例Rotor综合征患者的临床特点和SLCO1B1和SLCO1B3基因突变情况,从分子遗传学角度分析该疾病的发生机制。方法收集患者临床资料,从外周血白细胞提取基因组DNA,采用二代测序进行四千种已知单基因遗传性疾病筛查,用Sanger测序法分析验证二代测序发现的突变位点。结果患儿主要临床表现为反复皮肤及巩膜黄染,实验室检查示高胆红素血症,直接、间接胆红素双向增高。高通量测序发现患儿携带SLCO1B1基因c.1738 CT纯合突变和SLCO1B3基因c.360_481 del纯合突变。c.1738 CT突变为无义突变,已有文献报道,推测导致蛋白的第580位氨基酸密码子由精氨酸变为终止密码子。c.360_481 del突变为移码突变,蛋白编码区的第360至481位碱基缺失。该变异未见文献报道,也未见SNP数据库收录。此变异使蛋白缺失40个氨基酸的同时还造成开放阅读框移码,可能造成蛋白功能丧失。结论 SLCO1B1和SLCO1B3基因突变导致的有机阴离子转运多肽OATP1B1和OATP1B3功能缺陷是该Rotor综合征患者临床表现的分子遗传基础。     

SLCO1B1、ApoE基因多态性对瑞舒伐他汀治疗血脂异常超高危动脉粥样硬化性心血管疾病患者的影响

目的 探究SLCO1B1、载脂蛋白(Apo)E基因多态性对瑞舒伐他汀治疗血脂异常所致超高危动脉粥样硬化性心血管疾病(ASCVD)患者的影响。方法 268例血脂异常的超高危ASCVD患者,按照基因型检测结果分组。观察治疗前后各组总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、血清肌酐(Cr)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、肌酸激酶(CK)水平,研究期间患者肌痛发生情况。结果 所有入组患者中ApoE等位基因分布为e2 25例,e3 201例,e4 42例;基因型分布：E2/E2 6例,E2/E3 29例,E3/E3 150例,E2/E4 9例,E3/E4 73例,E4/E4 1例。SLCO1B1中521 T/C位点基因型分布分别为：TT 190例,TC 66例,CC 12例;SLCO1B1中388 A/G位点基因型分布分别为：AA 8例,AG 100例,GG 160例。符合Hardy-Weinberg平衡定律(P>0.05)。治疗前,TC+CC组与TT组各指标比较差异无统计学意义(P>0.05);治疗后,TC...     

ApoE基因与人类老年性疾病的关系及ApoE基因敲除小鼠在人类老年疾病研究中的应用

心脑血管疾病的病因与发病机制非常复杂,病毒因素、遗传因素、染色体及免疫功能都与其相关.目前已经发现多个基因与心脑血管疾病发生有关,其中,载脂蛋白E(Apo E)基因在心脑血管疾病中的作用被越来越多的认识.国外通过对大规模的人群进行分析,发现ApoE基因的多态性和老年性疾病息息相关[1].     

血脂水平与载脂蛋白E和SLCO1B1基因多态性与晚期支架内再狭窄的相关性研究

目的 对比分析晚期支架内再狭窄(in-stent restenosis,ISR)与无ISR患者的临床特点、血脂水平、载脂蛋白E(apolipoprotein E,ApoE)以及SLCO1B1基因的多态性,探讨影响晚期ISR的临床危险因素.方法 入选2018年1月至2020年12月我院行冠状动脉造影证实晚期ISR的患者共...     

血脂水平、ApoE和SLCO1B1基因多态性与晚期支架内再狭窄的相关性研究

目的 对比分析晚期支架内再狭窄(in-stent restenosis, ISR)与无ISR患者的临床特点、血脂水平、载脂蛋白E (apolipoprotein E, ApoE)以及SLCO1B1基因的多态性,探讨影响晚期ISR的临床危险因素。方法 入选2018年1月至2020年12月住院行冠状动脉造影证实晚期ISR的患者共61例,另外入选行冠状动脉造影证实无晚期ISR的患者共119例为对照组。比较两组的临床特点、血脂水平以及ApoE以及SLCO1B1基因的多态性。所有患者根据低密度脂蛋白胆固醇（low-density lipoprotein cholesterol, LDL-C）水平分为＜1.4mmol/l组,1.4~1.8 mmol/L组以及＞1.8 mmol/L组,=比较不同组别晚期ISR的发生率。结果 晚期ISR组与无ISR组患者ApoE、SLCO1B1基因型以及等位基因的频率并无统计学差异（P＞0.05）,将不同基因型和等位基因频率分别进行组内两两对比,结果也无统计学差异（P＞0.05）。两组患者总胆固醇(total cholesterol ,TC)、LDL-C、载脂蛋白B(apolipoprotein B, ApoB)、ApoB/ApoA比值以及非高密度脂蛋白胆固醇（non-high-density lipoprotein cholesterol, n-HDL-C）水平均有统计学差异,晚期ISR组上述指标均比对照组偏高（P<0.05）。3. ＜1.4 mmol/L组的ISR发生率为17.9%,1.4~1.8mmol/l组的ISR发生率为31.3%,＞1.8 mmol/L组的ISR发生率为39.4%。不同LDL-C水平的组间总体ISR发生率并无统计学差异（P＞0.05）。进一步行组间两两对比,小于＜1.4mmol/l组的ISR发生率为与＞1.8mmol/l组的ISR发生率有差异（P<0.05）。 结论 冠状动脉支架术后的患者,其ApoE或SLCO1B1的基因多态性与晚期ISR的发生率无明确关系。晚期ISR患者血脂水平较无ISR患者升高明显,将LDL-C降至1.4mmol/l以下可能有助于减少晚期ISR的发生。     

Polymorphisms in drug transporter genes (ABCB1, SLCO1B1 and ABCC2) and hepatitis induced by antituberculosis drugs

Unusual drug accumulation is a common mechanism underlying serious drug-induced liver injury. Polymorphisms in three drug transporter genes (ABCB1, SLCO1B1 and ABCC2) may be risk markers for hepatitis induced by the unusual accumulation of anti-tuberculosis drugs (ATDs). We therefore investigated whether polymorphisms and haplotypes of these genes are associated with ATD-induced hepatitis by comparing the frequencies and distributions of single nucleotide polymorphisms and haplotypes of these three drug transporter genes among 67 patients with ATD-induced hepatitis and 159 patients tolerant to ATDs using a multivariate logistic regression analysis. We found that the frequencies of polymorphisms and haplotypes of ABCB1, SLCO1B1 and ABCC2 were similar in patients with ATD-induced hepatitis and ATD-tolerant controls. The present results suggest that these drug transporters do not play important roles in the pathogenesis of ATD-induced hepatitis in Korean patients.     

Genetic link with cholelithiasis among pediatric SCA Tunisian patients: Examples of UGT1A1, SLCO1A2 and SLCO1B1

Aims and background: Hyperbilirubinemia is often observed in chronic hemolysis and results in the formation of pigment cholelithiasis that could be increased by the presence of defected enzymes involved in the bilirubin metabolism. Indeed, this is the first report that interested in the study of polymorphisms in genes encoded for enzymes involved in the bilirubin metabolism: rs 4149056 of SLCO1B1 and rs4149000 of SLCO1A2 in combination with rs8175347 and rs887829 of UGT1A1 in order to find a correlation between the polymorphisms studied and the presence of gallstones in a population of sickle cell anemia (SCA) pediatric Tunisians.

Material and methods: Our study involved 102 unrelated Tunisian subjects. All SCA patients are children (less than 16 years old) and were characterized by hyperbilirubinemia and 52 of them have cholelithiasis. The polymorphisms of the candidate genes were analyzed for all subjects by PCR/sequencing. Genotype and allele frequencies between cases and controls were compared using Pearson's chi-square test with a significance threshold of P?<?0.05 (compare 2, version 1.02).

Results: The novelty of this report is that children carrying the combined genotype of the rs studied: (TA7TA7)/TT/TC/GA have a higher risk to develop gallstones (P?=?0.0027, RR?=?18.27 (20.0061–915.28)).

Conclusion: Altogether our data provide the implication of UGT1A1 and SLCO1A2 in sickle cell anemia-related cholelithiasis.     

Effects of statin treatments and polymorphisms in UGT1A1 and SLCO1B1 on serum bilirubin levels in Chinese patients with hypercholesterolaemia

ObjectivesIn vitro and animal studies showed that statins could increase bilirubin levels by activation of haem oxygenase-1, whereas the effect of statins on serum bilirubin levels in humans remains controversial. The organic anion transporting polypeptide 1B1 (OATP1B1, gene SLCO1B1) and UDP-glucuronosyltransferase 1A1 (UGT1A1) play an important role in the disposition of bilirubin. This study investigated 1) whether common polymorphisms in UGT1A1 and SLCO1B1 influence bilirubin levels; 2) whether statin treatments affect bilirubin levels; and 3) whether the polymorphisms examined influence the drug effect.MethodsAssociations between common polymorphisms in UGT1A1 and SLCO1B1 and the serum bilirubin levels on no lipid-lowering treatment were analyzed in 379 Chinese patients with hypercholesterolaemia. Effects of simvastatin 40 mg daily and rosuvastatin 10 mg daily on the bilirubin levels were compared in 236 subjects with good compliance to both statins.ResultsThe UGT1A1 polymorphisms associated with reduced enzyme activity were significantly associated with increased baseline bilirubin levels. The bilirubin levels were increased from a geometric mean (95% CI) of 10.9 (10.3–11.4) μmol/L at baseline to 11.6 (11.1–12.0) μmol/L with rosuvastatin and 12.5 (11.9–13.0) μmol/L with simvastatin and the increase was greater with simvastatin (P < 0.001). There was no relationship between polymorphisms in UGT1A1 or SLCO1B1 and changes in bilirubin levels with the two statins.ConclusionsThis study showed that the polymorphisms in UGT1A1, but not SLCO1B1, were associated with serum bilirubin levels in Chinese patients. Statins increased bilirubin levels and this effect was independent of the polymorphisms in UGT1A1 and SLCO1B1.     

Polymorphisms of the macrophage inflammatory protein 1 alpha and ApoE genes are associated with ulcerative colitis

Background and aims  An increased production of macrophage inflammatory proteins 1 alpha (MIP-1α) has been reported to be associated with ulcerative colitis (UC). We investigated whether a polymorphism site in MIP-1α was associated with UC in a Chinese population. Additionally, considering the abnormal lipoprotein metabolism in subjects with UC, we also sought to determine whether genetic variation in the apolipoprotein E (ApoE) gene may play a role in the development of UC. Materials and methods  We examined the MIP-1α −906 (TA)₄/(TA)₆ polymorphism and the ApoE polymorphism in a cohort of 162 unrelated UC patients and 220 healthy controls by using restriction fragment length polymorphism assay. Results  A significantly increased frequency of the MIP-1α −906 (TA)₆/(TA)₆ genotype (P = 0.0031, odds ratio [OR] = 1.851, 95% confidence interval [CI] 1.228–2.791), as well as of the ApoE ε4+ genotype (P < 0.001, OR = 2.869, 95% CI 1.768–4.657), in patients with UC was proven. Moreover, the carriage of both MIP-1α −906 (TA)₆/(TA)₆ genotype and ApoE ε4+ genotype confers greater risk for the development of UC (P < 0.001, OR = 5.432, 95% CI 2.761–10.689). Conclusion  These findings suggest that variation in the MIP-1α and ApoE genes and their interaction may increase susceptibility to UC. Identifying these novel susceptibility genes, as well as their interactions, will help our understanding of the disease mechanisms of UC and may identify targets for developing novel treatment measures.