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,...     

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...     

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...     

郑州地区SLCO1B1和ApoE基因多态性分布情况

目的 调研SLCO1B1与载脂蛋白E（ApoE）基因多态性在郑州地区的分布情况,评估其对服用他汀类药物的风险。 方法 入选2018年7月～2019年7月间在河南省中医院1037例心脑血管疾病住院患者,应用荧光探针-PCR技术检测全血中SLCO1B1与ApoE基因型。统计分析其基因型在受检者的年龄和性别中的分布特点,对比分析其他地区的相关数据。 结果 发现受检患者中SLCO1B1 I类基因型(*1a/*1a+*1a/*1b+*1b/*1b）、II类基因型（1a/*5+*1a/*15+*1b/*15）和III类基因型（*5/*5+*5/*15+*15/*15）分别占75.6%、22.7%和1.6%;ApoE E2基因型（E2/E2+E2/E3）、E3基因型（E2/E4+E3/E3）和E4基因型（E3/E4+E4/E4）分别占13.6%、70.5%和15.9%。分析发现SLCO1B1和ApoE基因型组合在年龄和性别间分布差异均无统计学意义,与武汉、长沙、广州地区心脑血管疾病患者相比,郑州地区SLCO1B1和ApoE基因型组合分布差异无统计学意义。 结论 郑州地区心脑血管疾病患者SLCO1B1和ApoE基因多态性分别以I类基因型和E3基因型为主,且两种基因型各组合均不受年龄及性别的影响,基因型组合分布无地域特征。     

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。     

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。     

载脂蛋白B基因多态性及血脂水平与慢性丙型肝炎的相关性

目的:探讨载脂蛋白B(Apo B)基因Xba Ⅰ位点多态性和血脂水平与慢性丙型肝炎之间的关系．方法:通过病例对照研究设计,采用聚合酶链式反应- 限制性片段长度多态性(PCR-RFLP)技术观察77例慢性丙型肝炎患者和62例健康对照者的Apo B基因Xba Ⅰ位点的多态性,采用全自动生化分析仪进行肝功、血脂水平的分析比较．结果:慢性丙型肝炎组和对照组Apo B基因Xba Ⅰ位点 X X-,X-X-基因型构成不等,慢性丙型肝炎组X 等位基因频率低于对照组(0．071 vs 0．121,P=0．136),且病例组中肝硬化组X 等位基因频率低于慢性肝炎组,但未显示统计学的显著差异．病例组中不同病毒载量组间 Apo B基因Xba Ⅰ位点基因型分布存在显著差异,HCV RNA≥80 000 copies／L组X 等位基因频率低于HCV RNA<80 000 copies／L组(0．048 vs 0．179,P=0．035)．病例组中X X-基因型的血清胆固醇(CHO)水平、低密度脂蛋白(LDL)水平及Apo B水平均高于X-X-组,而且 Apo B水平的差异具统计学显著性(P=0．019);血清高密度脂蛋白(HDL)水平低于X-X-组,但无统计学差异．慢性丙型肝炎患者血清Apo B水平和LDL水平与血清HCV RNA水平之间均呈直线负相关关系(分别为r= -0．538,P=0．005;r=-0．460,P=0．016),但与谷丙转氨酶(ALT)水平无相关性．结论:Apo B基因Xba Ⅰ位点的多态性与我国人群对 HCV的易感性没有直接联系,但与慢性丙型肝炎患者的病毒载量有关．X 等位基因频率可影响慢性丙型肝炎患者Apo B水平．慢性丙型肝炎患者血清LDL水平和 Apo B水平与血清HCV RNA水平显著相关．     

ApoE基因多态性与血脂水平及冠心病的关系

目的 探讨载脂蛋白基因多态性对血脂代谢的影响及冠心病的相关性。方法 对100例冠心病患者和50名正常对照者,采用酶法测定血浆脂质和载脂蛋白（Apo）水平。载脂蛋白E（ApoE）基因型采用聚合酶链反应－限制性片段长度多态性（PCR－RFLP）的方法。结果 冠心病组ApoE4／3基因型高于对照组（P＜0.05）,冠心病患者ApoE4/3基因型携带者总胆固醇和ApoB水平高于其它基因型者（P＜0.05）,其它血脂指标差异无显著性（P＞0.05）。结论 ApoE基因多态性对血脂水平有明显作用,ApoE4基因携带者冠心病的危险性增加。     

西北地区中老年人群ApoE基因分布特征及血脂水平与认知功能障碍的关系

目的 探讨我国西北地区中老年人群ApoE基因分布特征及其血脂水平与轻度认知障碍（MCI）、阿尔兹海默病（AD）患者发病的关系。方法 以门诊就诊和住院的陕西、甘肃、青海等地区患者为研究对象,根据MCI及AD诊断标准,从中筛查出MCI组120例,AD组64例,正常对照组65例;采用基因芯片法行ApoE基因型测定及血脂检测,并进行统计学分析。结果 本研究中6种基因型均有测出;所选3组人群的ApoE基因型分布符合Hardy-Weinberg遗传平衡定律;3组间的基因型分布E3/E3纯合子频率最高(72.3%),E2/E2型最少（1.5%）,其中,MCI组及AD组E3/E4和E4/E4基因型频率明显高于对照组,而E2/E3型则低于对照组(均P<0.05);MCI组与AD组之间的等位基因分布频率差异无显著性;从血脂水平与基因多态性关系上,AD组患者血清TC、LDL-C水平明显增高,与对照组比较,差异有显著性(P<0.05);MCI及AD组患者中ApoEε4基因型TC、LDL-C 水平明显高于ApoEε2基因型(P<0.05),组间对照显示MCI及AD组ApoEε4基因型TC、LDL-C水平均高于对照组(P<0.05),但MCI与AD组ApoEε4基因型TC、LDL-C水平无明显差异。结论 西北地区中老年人群的ApoE基因分布具有一定的地域特性,其人群MCI及AD的患病与ApoE基因的多态性及血脂水平存在一定的关联。     

Association of APOE-C1 gene cluster polymorphisms with gallstone disease

BACKGROUND: Genetic polymorphisms in apolipoprotein genes may be associated with alteration in lipid profile and susceptibility to gallstone disease. AIM: To find out the association of APOE HhaI and APOC1 HpaI polymorphisms with gallstone disease. SUBJECTS: HhaI polymorphism of APOE and HpaI polymorphism of APOC1 were analysed in DNA samples of 214 gallstone patients and 322 age- and sex-matched healthy controls. METHODS: For genotyping DNA samples of all study subjects were amplified using polymerase chain reaction, followed by restriction digestion. All statistical analyses were done using SPSS v11.5 and ARLEQUIN v2.0 softwares. RESULT: APOC1 HpaI polymorphism was found to be significantly associated with gallstone disease. Frequency of H2H2 was significantly higher (P = 0.017) in patients than in controls and it was imposing very high risk (OR 9.416, 95% CI 1.125-78.786) for gallstone disease. When data were stratified in male and female, H2H2 was associated (P = 0.011) with disease in females only. Analysis at allele level revealed no association. APOE HhaI polymorphism and APOE-C1 haplotypes showed no association with gallstone disease. CONCLUSION: APOC1 HpaI polymorphism is associated with gallstone disease and shows gender-specific differences. APOE HhaI polymorphism may not be associated with gallstone disease.     

Association of two apolipoprotein A-I gene MspI polymorphisms with lipid and blood pressure levels

INTRODUCTION: Two MspI polymorphisms in the ApoA-I gene (G-75A and C83T) have been shown to be associated with plasma HDL-cholesterol levels. METHODS: We used a PCR-based RFLP method to determine the association of these polymorphisms with lipid parameters in 271 non-diabetic, normotriglyceridaemic Chinese subjects, of whom 104 were patients with hypertension, with 10.2% having hypercholesterolaemia and the remainder were controls. RESULTS: As expected, the hypertensive group had higher blood pressure and indices of obesity, and a more adverse lipid profile. No differences in the ApoA-I G-75A genotype or allele frequency distributions between the controls and patients were identified. However, there was a significantly lower frequency of the CT genotype (p=0.012) and T allele (p=0.011) in the affected subjects with hypercholesterolaemia or hypertension. Similarly, blood pressure and triglyceride levels were significantly lower and HDL-cholesterol levels significantly higher in the subjects with the CT genotype compared to those with the CC genotype (p<0.05). However, the G-75A genotypes did not appear to influence the lipid or blood pressure levels. The -75A allele frequency was higher in our healthy controls than an equivalent Caucasian population (31.1% vs. 18.3%, p<0.001), whereas the 83T allele frequency was similar between the healthy Chinese and Caucasian groups. CONCLUSION: The 83T allele may be associated with a better lipid profile and blood pressure levels in this group of Chinese subjects.     

Association of apolipoprotein A5 gene polymorphisms and serum lipid levels

Background and aims

Apolipoprotein (APO) A5 gene polymorphisms have been associated with increased plasma triglyceride (TG), but the results are inconsistent. The present study was undertaken to detect the APOA5 gene polymorphisms and their associations with lipid profiles in the Guangxi Hei Yi Zhuang and Han populations.

Methods and results

Genotyping of the APOA5 −1131T>C, c.553G>T and c.457G>A was performed in 490 subjects of Hei Yi Zhuang and 540 participants of Han Chinese aged 15-89 years. The −1131C allele frequency was higher in high total cholesterol (TC) than in normal TC subgroups in both the ethnic groups (P < 0.05). The c.553T allele frequency was higher in high TG than in normal TG subgroups (P < 0.01), in high APOB than in normal APOB subgroups in Hei Yi Zhuang (P < 0.05), or in females than in males in Han (P < 0.01). The c.457A allele frequency in Han was higher in high TG than in normal TG subgroups, in low APOA1 than in normal APOA1 subgroups, in males than in females, or in normal APOB than in high APOB subgroups (P < 0.05-0.01). The levels of TC, low-density lipoprotein cholesterol and APOB in Hei Yi Zhuang were correlated with −1131T>C genotype or allele, and the levels of TG were associated with c.553G>T genotype (P < 0.05). The levels of TG, APOA1 and APOB in Han were correlated with c.457G>A genotype or allele, and the levels of TC were associated with −1131T>C allele (P < 0.05).

Conclusions

The differences in the lipid profiles between the two ethnic groups might partly result from different APOA5 gene-environmental interactions.     

ABCB1 gene polymorphisms and haplotype analysis in colorectal cancer

Purpose  The aim of this study was to determine the significance of three most common single-nucleotide polymorphisms (SNPs) of ABCB1 gene in the development of colorectal cancer and to estimate the influence of these SNPs to surviving patients' treatment combination adjuvant therapy 5-fluorouracil/leucovorin. Haplotype structure of ABCB1 was analysed, and degree of linkage disequilibrium (LD) between SNPs of ABCB1 was estimated. Materials and methods  Tumour specimens of 95 patients with colorectal cancer and blood samples of 95 healthy cases were studied. Genotyping of ABCB1 gene was performed by automated sequencing or polymerase chain reaction-restriction fragment length polymorphism method. Comparison of frequencies of alleles/genotypes/haplotypes between the studied group (colorectal cancer samples) and the control group (blood samples) were analysed. These results were correlated with the surviving patients after treatment of adjuvant chemotherapy. Results  Significant differences in ABCB1 _1236C>T (p = 0.00043) and ABCB1 _2677G>T/A (p = 0.04) genotype distribution and T₁₂₃₆ allele distribution (CT₁₂₃₆ or TT₁₂₃₆ vs CC₁₂₃₆; p = 0.0499, OR = 0.55, Fi–Yule coefficient = 0.14) were found. A strong LD between ABCB1 _1236C>T and ABCB1 _2677G>T/A SNPs (D′ = 0.621, r ² = 0.318) was detected. All SNPs were located in one haplotype block. There were significant differences in haplotype distributions between colorectal cancer patients and healthy population (p = 0.03). Significant differences in survival probability of colorectal cancer patients' treatment chemotherapy according to allele of ABCB1 _3435C>T was observed. Survival probability of patients with wild-type C₃₄₃₅ allele were higher than among patients without this allele (p = 0.04572). Conclusions  These results suggested that three studied SNPs of ABCB1 were located in one haplotype block. Differences in ABCB1 _1236C>T and ABCB1 _2677G>T/A genotypes and T₁₂₃₆ allele distribution between investigated populations indicate significant impact of these SNPs on risk of development of colorectal cancer. Polymorphism ABCB1 _3435C>T may be a prediction marker of cancer chemotherapy effectiveness. Differences in haplotype distributions between colorectal cancer patients and healthy population suggested that other potential SNPs, especially in regulatory region of ABCB1 gene, may influence P-glycoprotein expression and function.     

Apolipoprotein B gene polymorphisms are associated with lipid levels in men of South Asian descent.

Three polymorphic sites of the apolipoprotein B gene - the insertion/deletion signal peptide, XbaI and EcoRI sites - were examined in a sample of 107 healthy men and in 46 men with evidence of coronary heart disease selected from a large population survey of South Asians aged 40-69 in London, U.K. There were no significant differences in allele frequencies between cases and controls. Frequencies of the ins (insertion) and X- (absence of XbaI cutting site) alleles were higher in South Asians than in Europeans studied previously (South Asians versus Europeans ins: 0.80 vs. 0.68, P less than 0.025; X-: 0.71 vs. 0.47-0.56, P less than 0.001). The del allele was associated with higher levels of total cholesterol (P less than 0.05) and the X+ allele with lower levels of HDL cholesterol (P less than 0.05), and thus both polymorphisms were associated with differences in the ratio of HDL cholesterol to total cholesterol (ins/del, P less than 0.01; XbaI, P less than 0.001). Mean waist-hip girth ratio was lower in the 10 men homozygous for the X+ allele than in the 42 men with X-/X+ and 55 men with X-/X- genotypes; the means (+/- SEM) were 0.92 +/- 0.02, 0.97 +/- 0.01 and 0.96 +/- 0.01 respectively (P = 0.03). These data suggest that genetic variation in linkage disequilibrium with the XbaI and ins/del polymorphisms of the apo B gene contributes to the determination of total cholesterol and HDL cholesterol levels and possibly to obesity in South Asians.     

苏中苏南地区高脂血症人群ApoE基因多态性分析

目的 探讨江苏省苏中苏南地区汉族人群高脂血症患者中载脂蛋白E(ApoE)不同基因型的分布差异,从而对他汀类药物在高脂血症患者中的使用提供数据支持,为临床用药提供参考。方法 回顾性分析2019年8月至2022年1月于江苏省苏北人民医院或苏州大学附属第一医院诊断为高脂血症的676例患者的临床资料,对患者的ApoE 388T＞C(rs429358)、526C＞T(rs7412)相关基因位点的多态性进行了检测,并根据基因分型将患者分为ApoE2、ApoE3和ApoE4组。分析各组患者总体及不同性别ApoE基因多态性和基因型分布情况。采用SPSS 26.0统计软件进行数据分析。根据数据类型,分别采用方差分析或χ²检验进行组间比较。结果 3组患者共检出6种ApoE基因表型,由多到少分别为E3/E3 458例(67.75%),E3/E4 109例(16.12%),E2/E3 86例(12.72%),E4/E4 11例(1.63%),E2/E4 10例(1.48%),E2/E2 2例(0.30%)。ApoE基因突变符合Hardy-weinberg遗传平衡(P>0.05),所有纳入患者来源于同一个孟德尔遗传。ApoE基因型分布在不同性别之间差异无统计学意义(P>0.05)。结论 苏中苏南地区高脂血症人群ApoE的基因多态性分布不均匀,在不同性别中无显著差异,ApoE基因多态性分布特点对临床精准调脂治疗具有一定的参考价值。     

MicroRNA-938及其靶基因 TGFBR1单核苷酸多态性与出血性脑卒中的关联研究

目的探讨转化生长因子β受体1（TGFBR1）基因位点rs12346650及结合该基因的miR-938编码基因位点rs2505901单核苷酸多态性（SNP）与出血性脑卒中（HS）的关联。 方法采用病例-对照研究方式,以自2008年1月至2013年7月淮安市第一人民医院和淮阴区医院收治的239例急性HS患者为病例组,993例无脑卒中史的社区人群为对照组。收集性别、年龄、身高、体质量等基本人口信息,及糖尿病史、高血压病史,测量血压并检测血糖（GLU）、甘油三酯（TG）、胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）。采用聚合酶链式反应-限制性内切酶片段长度多态性（RFLP）的方法进行基因分型。 结果病例组和对照组间rs2505901和rs12346650的基因型、等位基因型频率差异均无统计学意义（P>0.05）。应用Logistic回归模型校正混杂因素年龄、性别、Ⅱ型糖尿病、TC、TG、HDL-C和LDL-C后,结果仍无统计学意义（P>0.05）。进一步按性别对两个位点与HS的关联性进行分层分析,男性中rs2505901位点显性模型有统计学意义[比值比（OR）=0.641,95%置信区间（CI）：0.417~0.984]。rs12346650位点相加模型和隐性模型均有统计学意义（OR=1.369,95%CI：1.020~1.836;OR=2.092,95%CI：1.243~3.520）。但校正混杂因素后,模型差异无统计学意义（P>0.05）。在女性人群中,而校正协变量后rs12346650位点隐性模型有统计学意义（OR=0.318,95%CI：0.114~0.891）。 结论本研究初步发现TGFBR1基因rs12346650、MIR938基因rs2505901多态性与HS存在关联。