花生四烯酸5-脂氧合酶激活蛋白基因多态性与心肌梗死关系的研究

目的探讨在中国北方汉族人群中花生四烯酸5-脂氧合酶激活蛋白(ALOX5AP)基因单核苷酸多态性T(8733)C与心肌梗死的关系。方法采用PCR-重测序法对随机选取的无亲缘关系的48例中国北方汉族个体进行ALOX5AP基因单核苷酸多态性筛查,对经冠状动脉造影证实的125例心肌梗死患者和158例正常对照者,采用聚合酶链反应?限制性片段长度多态性(PCR-RFLP)方法检测ALOX5AP基因T(8733)C多态性基因型和等位基因分布情况。结果通过筛查发现7个多态。心肌梗死患者ALOX5AP基因T(8733)C3种基因型(TT型、TC型和CC型)及C等位基因分布频率分别为35.2%、48.8%、16.0%和40.4%,正常对照者分别为32.9%、50.0%、17.1%和42.1%,其差异均无统计学意义(P>0.05);按性别分层进行亚组分析,心肌梗死患者与正常对照者ALOX5AP T(8733)C多态的基因型和等位基因频率差异亦均无统计学意义。结论ALOX5AP基因T(8733)C多态性与中国北方汉族人群心肌梗死的发生可能无关。     

人类腺病毒5型早期区域1 A激活基因阻遏子rs3753921多态性与中国北方汉族人群冠心病发病的关联研究

目的 探讨人类腺病毒5型早期区域1A激活基因阻遏子(cellular repressor of E1A-stimulated genes,CREG)基因rs3753921单核苷酸多态与中国北方汉族人群冠心病发病的相关关系.方法 对经冠状动脉造影证实的338例冠心病患者和287例健康对照者,采用聚合酶链反应-重测序法检测CREG基因rs3753921单核苷酸多态位点在两组间的基因型和等位基因分布.结果 CREG基因rs3753921单核苷酸多态3种基因型(TT型,CT型和CC型)在冠心病组分布频率分别为65.7%,30.2%和4.1%,在对照组分别为59.2%,35.5%和5.2%,两组间的基因型分布皆符合Hardy-Weinberg平衡定律,3种基因型在两组间的分布差异无统计学意义(P>0.05).C等位基因在冠心病组和对照组间的分布频率分别为19.2%和23.0%.差异亦无统计学意义(P>0.05).按性别及年龄分层进行亚组分析,CREG基因rs3753921单核苷酸多态的基因型和等位基因频率在冠心病组和对照组间差异无统计学意义.结论 CREG基因rs3753921单核苷酸多态性与中国北方汉族人群冠心病发病可能无相关关系.     

ALOX5、ALOX5AP基因多态性与髓系白血病易感性的关系

目的:探讨花生四烯5-脂氧合酶基因(arachidonate 5-lipoxygenase gene,ALOX5) rs2029253,rs2228064和rs2228065位点以及5-脂氧合酶激活蛋白基因(5-lipoxygenase activating protein gene,ALOX5AP)rs10507391和rs4769874位点的单核苷酸多态性(single nucleotide polymorphisms,SNP)与髓系白血病发病风险的相关性。方法:经医院伦理委员会批准、患者知情同意,选取150例髓系白血病患者为髓系白血病(ML)组,134例健康人群为对照组。提取基因组DNA,采用聚合酶链反应及限制性片段长度多态技术(PCR-RFLP)联合PCR产物直接测序法检测ALOX5、ALOX5AP基因5个位点的基因型。结果:ALOX5基因rs2029253位点在ML组和对照组中的A等位基因频率分别为43.0%和34.3%,而等位基因G的频率分别为57.0%、65.7%;基因型AA、AG和GG在ML组中的分布频率分别为32.2%,21.5%和46.3%,而在对照组中的分布频率分别为15.7%,37.3%和47.0%。基因型AA和等位基因A可能增加髓系白血病的发病风险(OR=2.26,95%CI:1.43-4.56,P0.05;OR=1.44,95%CI:1.02-2.03,P0.05);基因型AG与等位基因G可能降低对髓系白血病的易感性(OR=0.46,95%CI:0.27-0.78,P0.01;OR=0.69,95%CI:0.50-0.98,P0.05)。而ALOX5基因rs2228064、rs2228065位点多态性在ML组与对照组间的分布差异无统计学意义(P0.05)。ALOX5AP基因rs10507391位点等位基因A在髓系白血病组和对照组中频率分布分别为30.7%和36.2%;基因型AA、AT和TT在ML组中分布频率分别为1.3%,58.7%和40.0%,在对照组中的分布频率分别为9.7%,53.0%和37.3%;基因型AA可能降低髓系白血病的发病风险(OR=0.13,95%CI:0.03-0.57,P0.05);而ALOX5AP rs4769874位点基因型与等位基因分布频率在ML组与对照组间的分布差异无统计学意义(P0.05)。结论:ALOX5 rs2029253位点基因型AA、AG和等位基因A、G以及ALOX5AP rs4769874位点AA基因型与髓系白血病发病的遗传易感性相关。     

ALOX5AP基因单核苷酸多态性与缺血性脑卒中患者颈动脉斑块的相关性分析

目的探讨5-脂氧合酶激活蛋白(ALOX5AP)基因单核苷酸多态性与缺血性脑卒中患者颈动脉斑块的关系,为颈动脉斑块的缺血性脑卒中早期诊断、治疗和发病机制研究提供依据。方法选取737例缺血性脑卒中患者,按有无颈动脉斑块分为斑块组和无斑块组,应用多重聚合酶链反应(PCR)及基因序列分析技术分析各组患者ALOX5AP基因8个位点多态性分布情况。结果斑块组的甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、非高密度脂蛋白胆固醇(non-HDL-C)、收缩压和血葡萄糖(Glu)水平均明显高于无斑块组(P0.05)。对ALOX5AP基因8个位点基因型和等位基因频率分析发现,斑块组与无斑块组间差异无统计学意义(P0.05)。ALOX5AP基因8个位点组成的2个单倍型构成在斑块组与无斑块组间差异无统计学意义(P0.05)。结论 ALOX5AP基因多态性与缺血性脑卒中患者颈动脉斑块形成无关。     

五脂氧化酶激活蛋白基因多态性及冠心病易患风险

目的：探讨五脂氧化酶激活蛋白基因（-5lipoxygenase activating protein gene,ALOX5AP）突变与冠心病的关系。方法：采用高分辨率溶解曲线法（high resolution melting,HRM）分析150例冠心病患者和280例健康对照者ALOX5AP基因的单核苷酸多态性（SNPs）。结果：ALOX5AP的A22879C位点的CC基因型增加了冠心病3.691倍患病风险;T8733A位点的AA基因型增加了冠心病2.718倍患病风险;T8733A位点的TA杂合基因型增加了冠心病2.962倍患病风险。结论：ALOX5AP的A22879C位点和T8733A位点多态性是冠心病的易患风险因素。     

5-脂氧合酶激活蛋白基因多态性与中国汉族人群脑卒中遗传相关性研究

目的 探讨5-脂氧合酶激活蛋白(ALOX5AP)基因的SG13S114和SG13S32两个SNP位点多态性与中国汉族人群脑卒中的相关性.方法本研究共纳入507例脑卒中患者(动脉粥样硬化性脑梗死158例,腔隙性脑梗死243例,脑出血106例)和513例对照组人群.采用聚合酶链式反应(PCR)和限制性片段长度多态性(RFLP)技术检测基因的多态性.运用SPSS16.0软件进行基因型、等位基因和单倍型等的关联分析.多元素Logistic回归方法调整传统危险因素后分析基因多态性与脑卒中发病风险的独立相关性.结果 SG13S114和SC13S32位点等位基因频率和基因型频率在病例组与对照组间比较差异无统计学意义.但经传统危险因素高血压分层后,SG13S114 TT基因型能够显著降低无高血压人群患脑卒中的发病风险(OR=0.54,95% CI0.30～0.98).两位点单倍型构成在脑卒中组及其各亚型组与对照组间比较差异无统计学意义.结论本地区中国汉族人群中ALOX5AP基因SG13S114和SG13S32两个位点多态性与脑卒中无显著关联,而SG13S114 TT基因型能显著降低无高血压人群脑卒中的发病风险,提示该基因可能与本地区无高血压人群脑卒中发病相关.     

载脂蛋白A5基因多态性与冠心病的相关性研究

目的研究太原汉族人群中载脂蛋白A5(ApoA5)-1131T/C基因多态性与冠心病(CHD)的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测了249例CHD患者和176例健康人群的ApoA5-1131T/C的多态性基因型和等位基因的分布。结果两组间ApoA5-1131T/C等位基因和基因型频率存在明显差异,等位基因C的频率在CHD组显著低于对照组(37.1%VS42.0%,P<0.05)。结论 ApoA5的基因多态1131T/C与CHD的发病率有一定的相关性(P<0.05)。     

中国北方汉族人群TRIB1基因rs2235108多态性与2型糖尿病合并冠心病的相关性

目的探讨中国北方汉族人群TRIB1基因rs2235108多态性与2型糖尿病(T2DM)合并冠心病(CHD)的关系。方法用PCR-限制性片段长度多态性(PCR-RFLP)检测了147例健康人对照组、96例T2DM组和75例T2DM合并CHD组TRIB1基因rs2235108多态性基因型和等位基因频率分布,分析基因多态性对T2DM和T2DM合并CHD的影响。结果我国北方汉族人群TRIB1基因rs2235108多态性CC基因型频率为81.8%,CT+TT为18.4%,C、T等位基因频率分别为90.5%、9.5%。3组研究对象的TRIB1基因rs2235108多态性基因型和等位基因频率分布差异无统计学意义(P>0.05)。3组内不同基因型间各项生化指标差异均无统计学意义(P>0.05)。logistic回归分析显示,年龄、HDL-C、高血压病史是T2DM合并CHD的独立危险因素。结论 TRIB1基因rs2235108多态性与T2DM合并CHD无明显关联性,不是我国北方汉族人群T2DM合并CHD发病的独立危险因素。     

ALOX12基因多态性与糖尿病和糖尿病肾病的相关性研究

目的研究ALOX12基因位点rs1126667(R261Q)单核苷酸多态性(SNP)与2型糖尿病(T2DM)及糖尿病肾病(DN)的相关性。方法在北方汉族人群中采用病例-对照方法选择223例T2DM患者(其中DN 134例、T2DM无肾病89例)和120名健康体检者(正常对照组)。应用单碱基延伸反应和基质辅助激光解吸电离飞行时间质谱技术对该基因SNP进行研究。结果 ALOX12基因rs1126667位点符合Hardy-Weinberg平衡定律。正常对照组G/G、G/A、A/A 3种基因型的频率为26%、47%和27%;T2DM组的频率分别为30%、48%和22%,相对危险度(OR)分别为1、0.8、0.76;DN组的频率分别为31%、45%和24%,OR值分别为1、0.88、0.94;T2DM无肾病组的频率分别为28%、54%和18%,OR值分别为1、1.06、0.61,各组间差异均无统计学意义(P0.05)。正常对照组、T2DM组、DN组和T2DM无肾病组A等位基因频率分别为50%、46%、47%、45%,各组间差异无统计学意义(P0.05)。结论在北方汉族人群中未发现ALOX12基因多态性与T2DM、DN有关。     

中国北方汉族人群TRIB1基因rs17321515多态性与2型糖尿病的相关性研究

目的 探讨中国北方汉族人群TRIB1基因rs17321515多态性与2型糖尿病的关系.方法 应用聚合酶链反应限制性片段长度多态性(PCR-RFLP)技术检测了148例对照组,98例2型糖尿病组和76例2型糖尿病并发冠心病组TRIB1基因rs17321515多态性基因型,分析了不同组间基因型和等位基因频率分布特点,并探讨了基因多态性对糖化血红蛋白(HbA1c)、血糖、血脂水平的影响.结果 三组研究对象间的TRIB1基因rs17321515多态性基因型和等位基因频率分布差异无统计学意义(P>0.05).中国北方汉族人群rs17321515多态性基因型AA,AG,GG频率分别为0.151,0.500,0.349,A,G等位基因频率分别为0.401,0.599,与不同国家地区间人群分布差异无统计学意义(χ2=3.543,P=0.471).2型糖尿病并发冠心病组中AG+GG基因型患者TG水平明显高于AA型,差异有统计学意义(P<0.05).未发现TRIB1基因rs17321515多态性与性别相关.Logistic回归分析显示,A等位基因是2型糖尿病并发冠心病的危险因素(95%CI=1.032～4.742,OR=2.212,P=0.041).结论 TRIB1基因rs17321515多态性与2型糖尿病并发冠心病有关联,A等位基因可能是我国北方地区汉族人群2型糖尿病并发冠心病发病的危险因素.     

Haplotype-based association of four lymphotoxin-alpha gene polymorphisms with the risk of coronary artery disease in Han Chinese

Lymphotoxin-alpha (LTA), a pro-inflammatory cytokine, has been implicated in the pathogenesis of coronary atherosclerosis. Meanwhile, association of some single nucleotide polymorphisms (SNPs) of LTA gene with coronary artery disease (CAD) has been evaluated; however, the results are irreproducible. We therefore investigated the relationship between four SNPs of LTA gene and CAD in Han Chinese: G+10A (rs1800683, 5'-untranslated region), A+80C (rs2239704, 5'-untranslated region), T+496C (Cys13Arg, rs2229094, exon 2), and C+804A (Thr26Asn, rs1041981, exon 3). Genotyping was performed in 438 CAD patients and 330 healthy controls. Single-locus analysis showed that the genotype and allele frequencies of G+10A polymorphism exhibited marginal differences between CAD patients and controls, although no statistical significance was observed after the Bonferroni correction. Logistic regression analysis revealed that GG genotype of G+10A polymorphism was significantly associated with the risk of CAD under the dominant mode, whereas no significant association was detected between A+80C polymorphism and CAD. In contrast, individuals carrying TT or TC genotype of T+496C polymorphism showed a decreased CAD risk relative to those with CC genotype under the recessive mode. Likewise, CC genotype of C+804A polymorphism was associated with a protective effect on CAD under the dominant mode. Further, in haplotype analysis, the haplotype G-C-T-C (in order of rs1800683, rs2239704, rs2229094 and rs1041981) was significantly associated with a decreased risk of CAD after assigning the most common haplotype A-C-T-A as a reference. In conclusion, we show a protective effect of the haplotype G-C-T-C on the occurrence of CAD, suggesting the involvement of LTA in CAD pathogenesis.     

内皮型一氧化氮合酶基因多态性与冠心病的关联研究

目的对内皮型一氧化氮合酶(eNOS)基因-786T/C、4a4b、894G/T等3个多态性位点与中国汉族人群冠心病(CAD)发病的相关性进行联合研究。方法 148例中国汉族CAD患者和115例正常对照进行以下遗传学分析:应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和PCR技术分析2个单核苷酸多态性(SNP)位点即-786T/C和894G/T,以及1个可变串联重复序列(VNTR)位点4a4b,检测各位点基因型和等位基因频率,采用HaploView4.0及SPSS13.0软件经χ2检验比较两组间各位点基因型及等位基因频率的差异。结果 CAD组中eNOS基因-786T/C位点CC基因型频率以及4a4b位点4a/4a基因型频率明显高于对照组,差异有统计学意义(P<0.05)。CAD组和对照组在eNOS基因的894G/T位点等位基因和基因型频率分布均无统计学意义(P>0.05)。结论 eNOS基因-786T/C和4a4b多态性与中国汉族人群CAD存在关联,C等位基因和4a等位基因可能是CAD发病的危险因素。eNOS基因894G/T位点与CAD可能无关联。     

Endothelial nitric oxide synthase G894T gene polymorphism in Chilean subjects with coronary artery disease and controls

BACKGROUND: Nitric oxide (NO) from the endothelium, produced by oxidation of l-arginine to L-citruline for the action at the endothelial nitric oxide synthase (eNOS), is considered an important atheroprotective factor. The Glu298Asp (G894T) polymorphic variant of the eNOS gene has been implicated in the development of coronary artery disease (CAD). We investigated the association between occurrence of CAD documented by angiography and the G894T polymorphism of the NOS3 gene in Chilean individuals. METHODS: A total of 112 unrelated patients with diagnosis of CAD and 72 controls were included in this study. G894T gene polymorphism was analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: The frequency of TT homozygous genotype for G894T polymorphism was 7% in CAD patients and 1% in the control group. However, the genotype distribution and allele frequencies were not significantly different between CAD and control subjects (P>0.05). Moreover, the odds ratio for CAD associated with the T variant failed to reach statistical significance (OR=1.5; 95% CI: 0.87-2.59, P>0.05). CONCLUSION: These findings suggest that the G894T polymorphism of the eNOS gene was not associated with CAD in Chilean individuals.     

Vitamin D receptor gene polymorphism BsmI is not associated with the prevalence and severity of CAD in a large-scale angiographic cohort of 3441 patients

BACKGROUND: Recent studies found a relationship between Vitamin D and atherosclerosis. A common genetic polymorphism of the Vitamin D receptor (VDR) has been associated with coronary artery disease (CAD) in small study populations. To assess its influence on the prevalence and severity of CAD we studied a large-scale population. METHODS: A total of 3441 consecutive patients were referred for diagnostic coronary angiography. The BsmI Vitamin D receptor polymorphism was analyzed by polymerase chain reaction. Angiography was used to define phenotypes with clear coronary arteries (n = 775), coronary sclerosis (diameter stenosis < 50%; n = 579), CAD (diameter stenosis > 50% in at least one vessel; n = 1524). Patients with CAD at a young age (females aged less than 65 years, males aged less than 55 years; n = 563) were specially defined as premature CAD. The risk profile of traditional cardiovascular risk factors was obtained for every patient. RESULTS: The genotype frequencies of the VDR BsmI polymorphism did not differ between all four phenotypes (P = 0.756). The allele frequencies for the B allele were 0.43 vs. 0.44 vs. 0.42 vs. 0.45 in the four phenotypic groups (P = 0.827). All traditional cardiovascular risk factors (hypercholesterolaemia, smoking, hypertension, diabetes mellitus, severe obesity, male gender) were significantly (P < 0.001) associated with the angiographic phenotype. CONCLUSIONS: The VDR gene variant BsmI was not associated with prevalence and severity of CAD in a large-scale cohort phenotyped by angiography.     

Genetic variation in the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) is associated with myocardial infarction in the German population

Genetic variation in the genes ALOX5AP (arachidonate 5-lipoxygenase-activating protein) and LTA4H (leukotriene A4 hydrolase) has previously been shown to contribute to the risk of MI (myocardial infarction) and stroke in Icelandic and Scottish populations. Both genes encode proteins playing a role in the synthesis of the pro-inflammatory leukotriene B mediators, possibly providing a link between MI and inflammation. The aim of the present study was to investigate whether these associations could be confirmed in a large study of German MI patients. Two previously described four SNP (single nucleotide polymorphism) haplotypes of the ALOX5AP gene (termed haplotype A and B) and one SNP (rs2660899) of the LTA4H gene conferring the greatest risk of MI in previous studies were genotyped in 1211 unrelated MI cases from the German MI Family Study and in 1015 healthy married-in spouses serving as controls. Haplotype B in the ALOX5AP gene was associated with an increased risk of MI in the German population, confirming previously reported associations of this haplotype with CAD (coronary artery disease) in populations from Scotland and Italy. No association with the risk of MI was detected for haplotype A of the ALOX5AP gene or for SNP rs2660899 representing the LTA4H gene. In conclusion, haplotype B of the ALOX5AP gene is associated with an increased risk of MI in a large German study. The present study is the third independent report from a European population describing an increased risk of CAD for carriers of haplotype B of the ALOX5AP gene, which substantiates further a role of this gene in the pathogenesis of CAD in Europeans.     

新疆汉族GGCX基因rs11676382位点多态性与心房颤动的相关性研究

目的研究汉族GGCX基因rs11676382位点多态性与心房颤动(AF)的相关性。方法以200例汉族未服用华法林的心房颤动患者作为研究组,200例健康汉族患者作为对照组,所有患者均采集外周血提取基因组DNA,采用聚合酶链反应,限制性片段长度多态性技术(PCRRFLP)检查患者GGCX基因rs11676382多态性的基因型和等位基因频率分布,观察GGCX基因rs11676382多态性与心房颤动的关系。结果GGCX基因rs11676382位点在入选人群中的基因型及等位基因分别为CC、CG和GG型,其基因型频率在心房颤动组和对照组分别依次为82.5%、16.5%、1.0%和85.0%、0.5%、14.5%,分布趋势相同,差异无统计学意义(P0.05);C和G等位基因频率在心房颤动组和对照组分别为99.0%,1.0%和99.5%,0.5%,C和G等位基因频率在两组间的差异无统计学意义(P0.05)。结论 GGCX基因rs11676382多态性与未服用华法林的心房颤动无相关性。     

IL-16 rs11556218 gene polymorphism is associated with coronary artery disease in the Chinese Han population

Objective

Our aim was to investigate the association between IL-16 gene polymorphisms (rs4778889 C/T and rs11556218 G/T) and coronary artery disease (CAD).

Design and methods

The initial cohort consisted of 300 CAD patients and 397 controls from the Chinese Han population. Genotyping was performed by using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). The positive association between polymorphism and CAD was replicated in another independent cohort, which included 424 CAD cases and 332 controls.

Results

In the initial study, the allele and genotype frequencies of rs4778889 were not different between in CAD and controls (P > 0.05). However, The G allele frequency of rs11556218 was significantly higher in the CAD cases than in the controls (CAD, 46.8% vs. controls, 22.8%, P < 0.001). The risk of CAD was significantly higher in the G allele carriers than in the non-carriers (P < 0.001, adjusted odds ratio = 7.27; 95% confidence interval, 4.13–12.8). In the replication cohort, G carriers of rs11556218 also had a higher risk of CAD (P = 0.005, adjusted OR = 2.33; 95% confidence interval, 1.45–3.74).

Conclusion

Our study suggested that IL-16 rs11556218 G/T polymorphism is significantly associated with the risk of CAD in the Chinese Han population.     

ADRB2基因多态性与aSAH迟发性脑血管痉挛的 关联性研究

目的:探讨中国北方汉族人群中,动脉瘤性蛛网膜下腔出血(aSAH)后迟发性脑血管痉挛(DCVS)与β2肾上腺素能受体(ADRB2)基因多态性的关系。方法:aSAH患者206例纳入研究,按照是否合并DCVS分为DCVS组128例和无DCVS组78例,采用聚合酶链反应-限制性片段长度多态性法检测ADRB2基因A46G位点和C79G位点多态性。结果:单因素分析结果显示ADRB2基因A46G位点等位基因模型(A vs.G)和显性基因模型(A/A vs.A/G+G/G)均与DCVS发生相关;多因素Logistics回归分析结果显示ADRB2基因+46位点等位基因G和基因型(A/G+G/G)与aSAH患者发生DCVS的危险因素(OR=1.414,95%CI:1.142~4.817,P=0.039;OR=1.337,95%CI:1.076~3.191,P=0.045);C79G位点各基因模型与DCVS相关性均无统计学意义。结论:对于中国北方汉族aSAH患者,ADRB2基因A46G位点多态性与DCVS发生相关。