A Population Association Study of Four Candidate Genes (Hexokinase II,Glucagon-like Peptide-1 Receptor,Fatty Acid Binding Protein-2, and Apolipoprotein C-II) with Type 2 Diabetes and Impaired Glucose Tolerance in Japanese Subjects

In order to define the major genetic factor(s) for the development of Type 2 (non-insulin-dependent) diabetes mellitus in Japanese subjects, a population association study of candidate genes involved in either glucose or lipid metabolism was carried out using microsatellite DNA polymorphisms. Each polymorphic locus near the four candidate genes, hexokinase II (HKII), glucagon-like peptide-1 receptor (GLP1R), fatty acid binding protein-2 (FABP-2), and apolipoprotein C-II (apoC-II) genes, were amplified by polymerase chain reaction (PCR) using ³²P-labelled primers and each subject was genotyped for the association study. The HKII, GLP1R, FABP-2, and apoC-II polymorphisms exhibited 18, 10, 7, and 10 alleles, respectively. While polymorphism information contents (PICs) of these polymorphisms were relatively high, allele frequencies in these polymorphisms did not differ among subjects with Type 2 diabetes, impaired glucose tolerance (IGT) and non-diabetic controls. These results suggest that the HKII, GLP1R, FABP-2, and apoC-II genes are not the major inherited factors for the development of Type 2 diabetes or IGT in Japanese subjects, although minor contributions cannot be ruled out.     

长沙地区汉族人群载脂蛋白H基因多态性的研究

目的 探讨长沙地区汉族人群载脂蛋白H(apolipoproteinH，apoH)基因多态性的分布规律。方法 采用PCR-单链构象多态(single conformation polymorphism，SSCP)技术和DNA直接测序法检测100例长沙地区汉族正常人的apoH基因8个外显子的多态标记，并与其他人种进行比较。结果 发现长沙地区汉族人群apoH基因的4种位点多态性，其中3号外显子G341A(Ser88Asn)多态位点GG、GA和AA基因型频率分别为0.900、0．090和0．010，G和A等位基因频率分别为0．945和0．055；7号外显子G817T(Leu247Val)多态GG、GT和TT基因型频率分别为0．610、0．340和0．050，G和T等位基因频率分别为0．780和0．220；8号外显子G1025C(Try316Ser)多态GG、GC基因型频率分别为0．880和0．120，G和C等位基因频率分别为0．940和0．060；8号外显子C1080T多态CC、CT基因型频率分别为0．930和0．070，C和T等位基因频率分别为0．965和0．035。结论 长沙地区汉族人群apoH基因存在4种位点多态性，不同多态位点基因频率分布与其他人种比较有显著性差异。     

葛根总黄酮对载脂蛋白E基因缺陷小鼠动脉粥样硬化斑块形成的影响

目的探讨葛根总黄酮对载脂蛋白E基因缺陷小鼠主动脉窦动脉粥样硬化斑块形成的影响。方法将载脂蛋白E基因缺陷小鼠随机分为模型组、葛根总黄酮低剂量组、葛根总黄酮高剂量组及阿托伐他汀阳性药物组。常规生物化学法测定血清总胆固醇、甘油三酯及高密度脂蛋白胆固醇水平;采用主动脉根部连续石蜡切片、苏木素伊红染色观察组织形态学改变,测定载脂蛋白E基因缺陷小鼠主动脉窦动脉粥样硬化斑块大小、动脉粥样硬化斑块与管腔面积比。结果4组小鼠共检出斑块65个,4组虽都有典型的粥样斑块或/及纤维斑块等中晚期动脉粥样硬化病变形成,但组织学观察发现模型组部分斑块体积较大,汇合成片,管壁弥漫性增厚,管腔较狭窄,而葛根总黄酮治疗组及阿托伐他汀阳性药物组动脉粥样硬化斑块病变较局限,管腔狭窄程度较轻,并且葛根总黄酮高、低剂量组及阿托伐他汀阳性药物组斑块面积与管腔面积之比值显著低于模型组(分别为0.11%±0.04%、0.27%±0.04%和0.76%±0.33%,P<0.01),葛根总黄酮高剂量组斑块面积与管腔面积比值显著低于葛根总黄酮低剂量组(P<0.01)。结论葛根总黄酮一定程度抑制载脂蛋白E基因缺陷小鼠动脉粥样硬化斑块进展,该作用可能与降低小鼠血脂作用无明显关系。     

载脂蛋白E基因多态性与脑血管病的关系

目的　探讨载脂蛋白 E ( APOE)基因多态性与脑血管病 ( CVD)的关系。方法　应用聚合酶链反应—限制性长度多态性技术 ( PCR-RFLP) ,检测 30例脑出血 ( CH)及 6 3例脑梗死 ( CI)患者的 APOE基因型 ,并与 6 6名同龄健康对照组比较。结果　 CH组 APOE基因型ε4及ε4携带者的频率明显高于对照组 ( P<0 .0 5 ) ,ε3及ε3/3频率显著低于对照组 ( P<0 .0 1 ) ;CI组 APOE基因型 ε3/4明显高于对照组 ( P<0 .0 5 )。结论　 APOE基因 ε3/4与 CI的发生相关 ,等位基因 ε4可能是 CVD的一种遗传易感因子 ,ε3/3可能与 CVD的保护有关。     

Analysis of Plasma Albumin,Vitamin D,and Apolipoproteins A and B as Predictive Coronary Risk Biomarkers in the REGICOR Study

Introduction and objectives

New biomarkers could improve the predictive capacity of classic risk functions. The aims of this study were to determine the association between circulating levels of apolipoprotein A1 (apoA1), apolipoprotein B (apoB), albumin, and 25-OH-vitamin D and coronary events and to analyze whether these biomarkers improve the predictive capacity of the Framingham-REGICOR risk function.

载脂蛋白C3基因rs5128多态性与不同体质指数冠心病患者血脂水平及冠状动脉狭窄程度的相关性

目的探讨中国汉族人群载脂蛋白C3(ApoC3)基因rs5128多态性与不同体质指数(BMI)冠心病(CHD)患者血脂水平及冠状动脉狭窄程度的相关性。方法根据BMI将312例CHD患者分为正常体重组(205例)和超重/肥胖组(107例)。收集所有患者的生理生化资料和冠状动脉造影数据,采用Gensini评分法评价CHD患者的冠状动脉狭窄程度。提取外周血白细胞DNA并应用聚合酶链反应-限制性片段长度多态性法对ApoC3rs5128多态性分型。结果超重/肥胖组体重、BMI、高血压患病率、甘油三酯(TG)、脂蛋白a、TG/高密度脂蛋白胆固醇(HDLC)、总胆固醇(TC)/HDLC、低密度脂蛋白胆固醇(LDLC)/HDLC和载脂蛋白B100(ApoB100)/载脂蛋白AI(ApoAⅠ)水平高于正常体重组,HDLC和ApoAⅠ水平低于正常体重组(P0.05)。在正常体重组中,G等位基因携带者高血压患病率显著高于CC基因型患者(P0.05);在超重/肥胖组中,G等位基因携带者TG和TG/HDLC水平显著高于CC基因型患者(P0.05)。在正常体重组和超重/肥胖组中,rs5128多态性基因型和等位基因频率在不同冠状动脉狭窄程度亚组中的分布差异无统计学意义(P0.05)。结论在超重/肥胖CHD患者中,rs5128多态性G等位基因与血浆TG和TG/HDLC水平升高显著相关,但与冠状动脉狭窄程度无明显关联。     

Genetic association of apolipoprotein E polymorphisms with inflammatory bowel disease

AIM:To study the association of apolipoprotein E(APOE) polymorphisms with the susceptibility ofinflammatory bowel disease(IBD) in Saudi patients.METHODS:APOE genotyping was performed to evaluate the allele and genotype frequencies in 378 Saudi subjects including IBD patients with ulcerative colitis(n = 84) or Crohn's disease(n = 94) and matched controls(n = 200) using polymerase chain reaction and reverse-hybridization techniques.RESULTS:The frequencies of the APOE ε2 allele and ε2/ε3 and ε2/ε4 genotypes were significantly higher in IBD patients than in controls(P 0.05),suggesting that the ε2 allele and its heterozygous genotypes may increase the susceptibility to IBD.On the contrary,the frequencies of the ε3 allele and ε3/ε3 genotype were lower in IBD patients as compared to controls,suggesting a protective effect of APOE ε3 for IBD.The prevalence of the ε4 allele was also higher in the patient group compared to controls,suggesting that the ε4 allele may also increase the risk of IBD.Our results also indicated that the APOE ε4 allele was associated with an early age of IBD onset.No effect of gender or type of IBD(familial or sporadic) on the frequency distribution of APOE alleles and genotypes was noticed in this study.CONCLUSION:APOE polymorphism is associated with risk of developing IBD and early age of onset in Saudi patients,though further studies with a large-size population are warranted.     

载脂蛋白B、AⅠ及二者比值与缺血性卒中患者颅内动脉粥样硬化性狭窄的相关性

目的 探讨载脂蛋白(apolipoprotein B,ApoB)、载脂蛋白AⅠ(apolipoproteinA Ⅰ,ApoA Ⅰ)和ApoB/ApoA Ⅰ比值与缺血性卒中患者颅内动脉粥样硬化性狭窄(intracranial atherosclerotic stenosis,ICAS)的关系.方法 回顾性收集大动脉粥样硬化性卒中患者,基于血管影像学资料将患者分为ICAS组和非ICAS组,收集血压、血脂、血糖、ApoB、ApoA Ⅰ、ApoB/ApoA Ⅰ比值以及人口统计学资料,比较上述指标在两组之间的差异.结果 共纳入360例大动脉粥样硬化性卒中患者,ICAS组177例(49.2％),非ICAS组183例(50.8％).两组之间高血压、糖尿病和冠心病的患者构成比以及低密度脂蛋白胆固醇、ApoB、ApoA Ⅰ水平和ApoB/ApoA Ⅰ比值存在显著性差异(P均＜0.05).多变量logistic回归分析显示,高血压[优势比(odds ratio,OR)1.75,95％可信区间(confidence interval,CI)1.04 ～2.93;P=0.035]、糖尿病(OR 2.09,95％ CI 1.31 ～3.32;P=0.002)、冠心病(OR 2.68,95％ CI1.09 ～6.57;P=0.031)以及ApoB≥0.84 g/L(0.84 ～ 1.00 g/L:OR 2.68,95％ CI 1.30 ～ 5.56; 1.00 ～1.16 g/L:OR 3.95,95％ CI 1.87 ～8.40;＞ 1.00 g/L:OR6.41,95％ CI 2.82 ～ 14.49)和ApoB/ApoA Ⅰ比值≥0.60(0.60～0.73:OR 1.92,95％ CI 1.14 ～3.24;0.74～0.91:OR 1.79,95％ CI 1.06 ～3.02;＞0.91:OR 3.30,95％ CI 1.92 ～5.67)为ICAS的独立危险因素,而ApoA Ⅰ＞1.28 g/L为ICAS的独立保护因素(OR0.39,95％ CI0.16～0.98;P=0.044).结论 在急性缺血性卒中患者中,ApoB水平和ApoB/ApoA Ⅰ比值增高是ICAS的独立危险因素,而ApoA Ⅰ水平增高为ICAS的独立保护因素.ApoB/ApoA Ⅰ比值可作为中国人群缺血性卒中患者ICAS的生物学标记物.