PGC-1α基因多态性与冠心病的相关性分析

目的研究过氧化物酶体增殖物激活受体7共激活因子1α（PGC-1α）基因的单核苷酸多态性（single-nucleotidepolymorphism,SNP）住点rs2970847与中国汉族人群冠心痛（coronaryheartdisease,CHD）的相关性。方法本研究共选取中国汉族冠心病患者231人（男性151,女性80）,正常对照组478人（男性297,女性181）。采用限制性酶切片段长度多态性（Restriction Fragment Length Polymorphism,RFLP）的方法对rs2970847进行基因分型。并测定所有入选对象的体重指数、血糖、总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白等指标。结果冠心病患者中,rs2970847位点的CC基因型为144人（62．3％）,CT基因型为75人（32．5％）,TT基因型为12人（5．2％）;而正常对照中,CC基因型为235A-（49．2％）,CT基因型为201人（42．1％）,TT基因型为42人（8．8％）。rs2970847位点与冠心痛显著相关（P=0．0009）,纯合子CC基因型可以增加冠心病的患病风险（ORCC：2．14,95％CI=1．09-4．21）。结论PGC—1α基因多态位点rs2970847与冠心痛具有显著相关性,其CC基因型是冠心病的危险因素。     

IL-7RA基因rs6897932位点多态性与冠心病严重程度的相关性研究

目的探讨IL-7RA基因rs6897932位点多态性与冠心病严重程度的相关性。方法回顾性选取2018年1月至2020年12月在上海交通大学医学院附属瑞金医院古北分院和上海交通大学医学院附属瑞金医院心内科住院治疗的冠心病患者350例为冠心病组,另选同期在同医院经过冠状造影诊断非冠心病的患者160例为对照组。对受试者临床资料进行对比分析,限制性内切酶酶切将IL-7RA基因rs6897932位点多态性进行分型,采用χ2检验判断基因型分布是否符合Hardy-Weinberg平衡检验,同时分析IL-7RA基因rs6897932位点与冠心病以及冠心病严重程度的相关性。结果冠心病组和对照组中冠心病家族史、高血压史、饮酒、总胆固醇、高密度脂蛋白胆固醇、尿酸对比,差异无统计学意义(P> 0.05);冠心病组中年龄、男性占比、糖尿病史人数占比、高脂血症人数占比、空腹血糖、吸烟人数占比、甘油三酯、低密度脂蛋白胆固醇、同型半胱氨酸、B型钠尿肽和脂蛋白a水平均明显高于对照组,差异均有统计意义(P <0.05)。冠心病组和对照组IL-7RA基因rs6897932位点有C和T两种等位基因,CC、CT和T...     

rs1840680 single nucleotide polymorphism in Pentraxin 3: a potential protective biomarker of severe community-acquired pneumonia

ObjectiveSingle nucleotide polymorphisms (SNPs) of pentraxin 3 (PTX3) are associated with various outcomes of lung infections. This study aimed to analyze the relationship between PTX3 polymorphisms and the severity of community-acquired pneumonia (CAP).MethodsThis is a retrospective case-control study comprising 43 patients with severe CAP (SCAP) and 97 patients with non-severe CAP. Three SNPs in the PTX3 gene (rs2305619, rs3816527, and rs1840680) from peripheral blood samples were genotyped by real-time polymerase chain reaction. The association between each SNP and the CAP severity was analyzed by logistic regression analysis.ResultsWe found that the rs1840680 polymorphism was significantly associated with CAP clinical severity. However, no such association was observed for the genotypes and allele frequencies of rs2305619 or rs3816527. The PTX3 rs1840680 AG genotype was an independent factor for a lower risk of SCAP after multivariate logistic regression analysis. Male sex and coronary heart disease were associated with an increased risk of SCAP.ConclusionsThe PTX3 rs1840680 AG genotype was found to be associated with a lower risk of SCAP, and may serve as a potential protective biomarker to help clinical judgment and management.     

The genes of atherosclerosis and cardiovascular diseases

The aim of the work was to study polymorphism of atherosclerosis-related genes in patients with different forms of coronary heart disease (CHD) and chronic cerebral ischemia (CCI) in comparison with long-living subjects. Analysis included the distribution of genotypes and alleles of functional polymorphisms of lipid metabolism genes, viz. HindIII--polymorphism of lipoproteinase (LPL) gene; HhaI--polymorphism of apoE gene; TaqIB--polymorphism of cholesterol ether transfer protein (CETP) gene; I/D--polymorphism of angiotensin converting enzyme (ACE) in CHD and CCI patients of different age groups including long livers and those presenting with different clinical variants of CHD and CCI (FC II-III stable angina of effort, acute myocardial infarction, post-infarction cardiosclerosis, acute coronary syndrome) and control subjects. The study revealed potential molecular-genetic markers for primary and secondary prophylaxis of CHD and CCI. It was shown that DD genotypes of ACE gene, H+/+ of LPL gene and E3E4 are associated with an enhanced probability of myocardial infarction (IM) in CHD patients and can be regarded as high risk markers. The DD genotype is associated with an increased risk of recurrent MI, life-threatening post-IM complications and severe cardiac insufficiency as well as peculiar personality and behavioural traits (animosity and type A behaviour)--psychological risk factors of CHD and predictors of delayed application for medical aid. E2 allele of the ApoE gene and H allele of the LPL gene occur much more frequently in CHD patients aged above 90 years (long livers) than in younger subjects; hence, their value as markers of stable ischemic disease. Protective effect in terms of favourable clinical course of CCI and life expectancy is especially pronounced in subjects with a combination of genotypes with E2E3 + H+H-, E2E2 + H+H-, E3E3 + H-H-genes of ApoE and LPL. B2B2 genotype of CETP gene increases the risk of stable CCI and B1B1 genotype of CETP gene enhances predisposition to cardiovascular pathology.     

Chromosome 9p21.3 coronary heart disease locus genotype and prospective risk of CHD in healthy middle-aged men

BACKGROUND: We investigated whether chromosome 9p21.3 single-nucleotide polymorphisms (SNPs), identified in coronary heart disease (CHD) genome-wide association scans, added significantly to the predictive utility for CHD of conventional risk factors (CRF) in the Framingham risk score (FRS) algorithm. METHODS: In the Northwick Park Heart Study II of 2742 men (270 CHD events occurring during a 15-year prospective study), rs10757274 A>G [mean frequency G = 0.48 (95% CI 0.47-0.50)] was genotyped. Using the area under the ROC curve (A(ROC)) and the likelihood ratio (LR) statistic, we assessed the discriminatory performance of the FRS based on CRFs with and without genotype. RESULTS: rs10757274 A>G was associated with incident CHD, with an effect size as reported previously [hazard ratio in GG vs AA men of 1.60 (95% CI 1.12-2.28)], independent of CRFs and family history of CHD. Although the A(ROC) for CRFs alone [0.62 (95% CI 0.58-0.66)] did not increase significantly (P = 0.14) when rs10757274 A>G genotype was added [0.64 (95% CI 0.60-0.68)], including genotype gave better fit (LR P = 0.01) and including rs10757274 moved 369 men (13.5% of the total) into more accurate risk categories. To model polygenic effects, 10 hypothetical, randomly assigned gene variants, with similar effect size and frequencies were added. Two variants made significant A(ROC) improvements to the FRS prediction (P = 0.01), whereas further variants had smaller incremental effects (final A(ROC) = 0.71, P <0.001 vs CRFs; LR vs CRFs P <0.0001). CONCLUSIONS: Although overall, rs10757274 did not add substantially to the usefulness of the FRS for predicting future events, it did improve reclassification of CHD risk, and thus may have clinical utility.     

The influence of genotype on vascular endothelial growth factor and regulation of myocardial collateral blood flow in patients with acute and chronic coronary heart disease

Abstract

Objective: To test the hypothesis that mutations in the vascular endothelial growth factor (VEGF) gene are associated with plasma concentration of VEGF and subsequently the ability to influence coronary collateral arteries in patients with coronary heart disease (CHD). Methods: Blood samples from patients with chronic ischemic heart disease (n=53) and acute coronary syndrome (n=61) were analysed. Coronary collaterals were scored from diagnostic biplane coronary angiograms. Results: The plasma concentration of VEGF was increased in patients with acute compared to chronic CHD (p=0.01). The genotype frequencies differed significantly from Hardy-Weinberg equilibrium in three of 15 examined loci. Four new mutations in addition to the already described were identified. The VEGF haplotype did not seem to predict plasma VEGF concentration (p=0.5). There was an association between the genotype in locus VEGF-1154 and coronary collateral size (p=0.03) and a significant association between the VEGF plasma concentration and the collateral size (p=0.03). Conclusion: VEGF plasma concentration seems related to coronary collateral function in patients with CHD. The results did not support the hypothesis that polymorphisms in the untranslated region of the VEGF gene were associated with the concentration of circulating VEGF. Increased understanding of VEGF in the regulation of myocardial collateral flow may lead to new therapies in CHD.     

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。     

湖北汉族人群TRIB1基因多态性分布特征及其与冠心病的关联性分析

目的研究tribbles同源物1（果蝇）（TRIB1）基因内含子区和3′UTR区2个标签单核甘酸多态性（TagSNP）（内含子区：rs235110;3′UTR区：rs235108）与冠心病的关系及其在湖北省汉族人群中的分布特征。方法采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对湖北地区236名健康汉族人和139例冠心病患者的TRIB1基因单核苷酸多态性（SNP）进行分析。并用PCR产物纯化后测序验证酶切结果。同时检测研究对象的血浆三酰甘油（TG）和总胆固醇（TC）水平。结果TRIB1基因的2个TagSNPs的分布特征符合Hardy-Weinberg平衡定律（rs2235110：χ^2=0.481,P=0.488;rs2235108：χ^2=0.570,P=0.450）。TG水平在冠心病组rs2235110位点基因型亚组内,差异有统计学意义（P〈0.05）。上述多态性位点在冠心病患者和正常人群中的分布无差异。rs2235110具有中等多态信息量（PIC）（rs2235110位点PIC=0.368 7,H=0.487 5）,几乎达到其PIC的理论最大值。结论本研究人群的rs235108、rs235110各位点的基因型和等位基因频率可代表湖北省汉族人群的分布特征,与HapMap数据库中其他SNP构成单倍型联用可作为一个理想的遗传标记。但没有发现其与冠心病的相关性。     

中国人群雌激素受体α基因PvuⅡ位点多态性与冠心病相关性的Meta分析

目的系统评价中国人群雌激素受体α基因PvuⅡ位点多态性与冠心病的相关性。方法计算机检索CBM、CNKI、万方数据库、VIP及MEDLINE、Cochrane Library、EMbase、Springer、Ovid等数据库,收集中国人雌激素受体α基因PvuⅡ位点多态性与冠心病易感相关性的病例对照研究,检索时间从建库至2010年11月。在评价纳入研究质量并提取有效数据后,采用RevMan 5.0软件进行Meta分析。结果共纳入9个研究,包括冠心病1464例,对照人群1203例。Meta分析结果显示,就雌激素受体α基因PvuⅡ位点T/C多态性与冠心病相关性而言,C等位基因与T等位基因[OR=0.95,95%CI(0.77,1.17),P=0.63]、基因型TC+CC与TT[OR=0.97,95%CI(0.73,1.28),P=0.81]、基因型TC与TT[OR=0.93,95%CI(0.68,1.26),P=0.64]、基因型CC与TT[OR=0.869,5%CI(0.57,1.31),P=0.49]人群发生冠心病的风险差异均无统计学意义。结论现有研究证据显示,中国人群中雌激素受体α基因PvuⅡ位点多态性可能与冠心病易感性无关。     

SLC2A3 variants in familial and sporadic congenital heart diseases in a Chinese Yunnan population

BackgroundSolute carrier family 2 member 3 (SLC2A3), is a member of a superfamily of transport protein genes. SLC2A3 played an important role in embryonic development. Previous research reported SLC2A3 duplication was reportedly associated with congenital syndromic heart defects. However, it is not clear whether the gene is associated with non‐syndromic congenital heart disease. Our study aimed to elucidate the relationship between its variation and congenital heart disease.MethodsGenomic DNA extracted from the peripheral blood leukocytes of two families with CHD were sequenced with whole‐exome sequencing to identify variations, used Sanger sequencing to investigate SLC2A3 variants in 494 Chinese patients with CHD and 576 healthy unrelated individuals.ResultsIn members from the two families, three with CHD had the SLC2A3 (rs3931701) C > T variant. Of the 494 patients with CHD, 394 had gene variants (86 had the TT type and 308 had the CT type). Of the 576 healthy controls, 272 participants had gene variants (36 had the TT type and 236 had the CT type). The TT type [p < 0.0001, odds ratio (OR) =7.262, 95% confidence interval (CI) =4.631–11.388] and CT type (p < 0.0001, OR =3.967, 95% CI =2.991–5.263) of SLC2A3 (rs3931701) significantly increased the risk of sporadic ASD in a Chinese Yunnan population.ConclusionsSingle nucleotide variations of SLC2A3, particularly, the SLC2A3 (rs3931701) C > T variant increased the risk of CHD among the studied population.     

von Willebrand factor plasma levels,genetic variations and coronary heart disease in an older population

Summary. Background: High von Willebrand factor (VWF) levels are associated with an increased risk of coronary heart disease (CHD). However, it remains unclear whether VWF is causally related to the occurrence of CHD or primarily mirrors endothelial dysfunction, which predisposes to atherosclerosis and subsequent CHD. Objectives: Because VWF is largely determined by genetic factors, we investigated whether VWF antigen levels (VWF:Ag) and the risk of CHD are affected by common variations in the VWF gene. Methods: We included 7002 participants (≥ 55 years) from the large prospective population‐based Rotterdam Study in the discovery cohort. The extension cohort of the Rotterdam Study, consisting of 3011 participants, was used as a replication cohort. We determined VWF:Ag levels and genotype data of 38 single‐nucleotide polymorphisms (SNPs) in VWF. Subsequently, hazard ratios for CHD were calculated and genetic analyses were performed to assess the relationship between SNPs, VWF:Ag levels and CHD risk. Results: We identified and replicated three SNPs that were associated with VWF:Ag: rs216321 (β = 0.10 [95% confidence interval, CI, 0.06;0.13]) (Ala852Gln), rs1063856 (β = 0.05 [95% CI 0.03;0.07]) (Thr789Ala) and rs2283333 (β = 0.09 [95% CI 0.05;0.21]) (intron 15). However, genetic polymorphisms in the VWF gene were not associated with the risk of CHD. Conclusions: In this study we have shown that genetic variations in VWF strongly affect VWF plasma levels, but are not associated with the risk of CHD. Our findings therefore do not support a strong causal relationship between VWF and CHD in elderly individuals of ≥ 55 years, but suggest that VWF is primarily a marker of CHD.     

Congenital heart disease risk loci identified by genome-wide association study in European patients

Genetic factors undoubtedly affect the development of congenital heart disease (CHD) but still remain ill defined. We sought to identify genetic risk factors associated with CHD and to accomplish a functional analysis of SNP-carrying genes. We performed a genome-wide association study (GWAS) of 4034 White patients with CHD and 8486 healthy controls. One SNP on chromosome 5q22.2 reached genome-wide significance across all CHD phenotypes and was also indicative for septal defects. One region on chromosome 20p12.1 pointing to the MACROD2 locus identified 4 highly significant SNPs in patients with transposition of the great arteries (TGA). Three highly significant risk variants on chromosome 17q21.32 within the GOSR2 locus were detected in patients with anomalies of thoracic arteries and veins (ATAV). Genetic variants associated with ATAV are suggested to influence the expression of WNT3, and the variant rs870142 related to septal defects is proposed to influence the expression of MSX1. We analyzed the expression of all 4 genes during cardiac differentiation of human and murine induced pluripotent stem cells in vitro and by single-cell RNA-Seq analyses of developing murine and human hearts. Our data show that MACROD2, GOSR2, WNT3, and MSX1 play an essential functional role in heart development at the embryonic and newborn stages.     

Association study of genetic variants at TTC32‐WDR35 gene cluster with coronary artery disease in Chinese Han population

BackgroundTTC32‐WDR35 gene cluster has been genome‐wide significantly associated with coronary artery disease (CAD). However, the common variants in this region contributing to CAD risk remain elusive.MethodsWe performed a case‐control study enrolling 935 CAD cases and 935 age‐sex‐frequency‐matched controls from unrelated southwest Chinese Han population. Five variants were determined by TaqMan assay.ResultsThis study indicated that rs721932 CG genotype was associated with CAD risk (OR = 0.68, 95% CI: 0.54‐0.86; P = .001). Stratified analysis showed that the risk associated with rs12617744 AA genotype was robust in male (OR = 0.62, 95% CI: 0.42‐0.93, P = .02). The gene dosage of the risk allele at rs12617744 showed a significant association with left circumflex artery disease (P = .027) and the number of vascular lesions in patients (P = .034). Moreover, the gene dosage of rs721932 risk allele was associated with vascular lesion numbers (P = .048) and the progression of CAD (P = .028). Compared with carriers of major alleles, the AA genotype of rs12617744 and GG genotype of rs721932 were both associated with plasma HDL level (P = .009 and 0.004, respectively). Expression quantitative trait locus (eQTL) results showed significantly different TTC32 expression of subjects as a function of SNPs (rs2278528, rs7594214, and rs721932) genotype in the artery. Besides, FPRP analysis did support the strong links between polymorphisms and CAD risk.ConclusionsSNP rs721932 at TTC32‐WDR35 Gene Cluster was associated with CAD risk, and rs12617744 was associated with the risk of CAD among males. Both SNPs may contribute to the regulation of plasma HDL levels and possibly to the severity of CAD in Chinese Han population.     

Gelatinase B C(‐1562)T polymorphism in relation to ischaemic heart disease

Objective. Matrix metalloproteinases, such as gelatinase B, are important in connective tissue remodelling processes associated with atherogenesis and plaque rupture. The T allele of the gelatinase B C_(‐1562) T polymorphism has been reported to be associated with an almost 2‐fold increase in promoter activity and with the extent of coronary artery disease (CAD). The aim of this study was to analyse the relation of this gene variation to the risk and severity of CAD and the risk of myocardial infarction (MI). Material and methods. This case‐control study comprised 535 healthy controls and 2731 participants who had undergone coronary angiography. Results. In the total sample, the gelatinase B promoter polymorphism was not associated with the risk of CAD and MI or with the extent of CAD defined either by the number of diseased coronary arteries or – in patients with coronary angiography – by a score for coronary heart disease (CHD) according to the Gensini score. However, patients with TT genotype had higher CHD scores than the other genotypes in subgroups of individuals with high apolipoprotein B levels, high lipoprotein (a) plasma concentrations and high fibrinogen levels, or with combinations of increased levels of these coronary risk factors. These observations were made in the entire sample of individuals with coronary angiography and in the population of patients with documented CHD. Conclusions. Obviously, the gelatinase B C_(‐1562)T gene polymorphism is not a risk indicator for CAD and MI. With respect to the extent of CHD, the impact of this gene variation may be restricted to individuals with high apolipoprotein B, lipoprotein (a) and/or fibrinogen levels.     

白细胞介素6基因-174G/C和-634C/G多态性与冠心病的相关性研究

目的探讨白细胞介素6(interleukin6,IL6)基因启动子上游174G/C和634C/G基因多态性,在冠心病患者和正常人群中的分布及与冠心病的相关性。方法应用聚合酶链反应限制性片断长度多态性技术,对汉族199例冠心病患者及189名正常人群,白细胞介素6基因174G/C、634C/G位点进行研究,同时结合血脂、脂蛋白和载脂蛋白水平,探讨两者之间的关系。结果正常人群和冠心病患者的174G等位基因频率均为0.99。174C等位基因频率均为0.01。634C等位基因频率在正常人群和冠心病患者分别为0.82和0.76,G等位基因频率分别为0.18和0.24,两者差异有统计学意义(P<0.05)。冠心病患者634GG基因型频率(0.08)明显高于对照组(0.02)(P<0.05)。结论白细胞介素6基因174位点多态性与冠心病无关,而634位点多态性与冠心病有相关性。G等位基因可能是汉族人群冠心病的易感性标志。     

江苏地区汉族人群CD14启动子C(-260)T多态性与冠心病的相关性研究

目的 分析江苏地区汉族人群白细胞分化抗原14(CD14)基因启动子C(-260)T多态性与冠心病之间的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术分析193例经冠脉造影确诊的冠心病患者及225例健康对照者CD14基因启动子-260位点多态性.并分别采用生化方法和ELISA法检测研究对象的血脂和外周血sCD14水平.结果 CD14启动子-260多态性位点基因型分布和等位基因频率在冠心病组和对照组间比较均无统计学差异(P均＞0.05).结论 CD14基因启动子C(-260)T位点多态性与江苏地区汉族人群冠心病不存在相关性,它可能不是汉族人群冠心病发病的遗传学易感因素.     

促酰化蛋白基因301T>C多态性与新疆维吾尔族冠心病及血脂的关系

目的探讨促酰化蛋白(acylation stimulating protein,ASP)基因301T>C多态性与新疆地区维吾尔族冠心病及血脂的关系。方法 385例冠心病患者(冠心病组)与483例冠状动脉造影结果阴性患者(对照组),2组采用聚合酶链反应-限制性片段长度多态性技术检测301T>C多态性,并检测其血脂水平。结果冠心病组ASP基因301T>C的3种基因型分布频率分别为TT型44.7%、CT型43.1%、CC型12.2%;对照组分别为TT型53.8%、CT型40.2%、CC型6.0%,2组基因型分布差异有统计学意义(P<0.01);Logistics回归分析结果显示,CC基因型个体患冠心病风险是TT基因型的0.784倍(OR=2.189,95%CI:1.251～3.830);冠心病组301T>C基因型亚组间三酰甘油水平差异有统计学意义(P<0.05);CC基因型三酰甘油水平高于TT基因型(P<0.05)。结论 ASP基因301T>C多态性与新疆维吾尔族人群冠心病的发生有一定相关性,CC基因型可能是冠心病发生的危险因素之一。     

Gelatinase B C(-1562)T polymorphism in relation to ischaemic heart disease

OBJECTIVE: Matrix metalloproteinases, such as gelatinase B, are important in connective tissue remodelling processes associated with atherogenesis and plaque rupture. The T allele of the gelatinase B C((-1562)) T polymorphism has been reported to be associated with an almost 2-fold increase in promoter activity and with the extent of coronary artery disease (CAD). The aim of this study was to analyse the relation of this gene variation to the risk and severity of CAD and the risk of myocardial infarction (MI). MATERIAL AND METHODS: This case-control study comprised 535 healthy controls and 2731 participants who had undergone coronary angiography. RESULTS: In the total sample, the gelatinase B promoter polymorphism was not associated with the risk of CAD and MI or with the extent of CAD defined either by the number of diseased coronary arteries or--in patients with coronary angiography--by a score for coronary heart disease (CHD) according to the Gensini score. However, patients with TT genotype had higher CHD scores than the other genotypes in subgroups of individuals with high apolipoprotein B levels, high lipoprotein (a) plasma concentrations and high fibrinogen levels, or with combinations of increased levels of these coronary risk factors. These observations were made in the entire sample of individuals with coronary angiography and in the population of patients with documented CHD. CONCLUSIONS: Obviously, the gelatinase B C((-1562))T gene polymorphism is not a risk indicator for CAD and MI. With respect to the extent of CHD, the impact of this gene variation may be restricted to individuals with high apolipoprotein B, lipoprotein (a) and/or fibrinogen levels.     

冠心病患者肝X受体基因多态性研究

目的 探讨肝X受体基因-115A（rs12221497）和-6A（rs11039155）多态性位点与冠心病遗传易感性的关系.方法 采用单荧光标记探针技术检测243例冠心病患者、256例正常对照组肝X受体基因-115A和-6A基因型.结果 （1）AA基因型携带者与GA基因型携带者患冠心病的风险为GG基因型携带者的1.732倍（ P〈0.05）, -115A等位基因携带者患冠心病的风险是-115G等位基因携带者的1.81倍（ P〈0.01）;（2）Logistic回归分析提示,-115A位点等位基因A是冠心病的独立危险因素;（3）汉族人群不存在LXR-6A（rs11039155）这一SNPs位点.结论 肝X受体基因-115A（rs12221497）多态性与汉族人群冠心病遗传易感性独立相关.     

Haplotype and genotype effects of the F7 gene on circulating factor VII,coagulation activation markers and incident coronary heart disease in UK men

Background: Evidence for the associations of single nucleotide polymorphisms (SNPs) in the F7 gene and factor (F)VII levels and with risk of coronary heart disease (CHD) is inconsistent. We examined whether F7 tagging SNPs (tSNPs) and haplotypes were associated with FVII levels, coagulation activation markers (CAMs) and CHD risk in two cohorts of UK men. Methods: Genotypes for eight SNPs and baseline levels of FVIIc, FVIIag and CAMs (including FVIIa) were determined in 2773 healthy men from the Second Northwick Park Heart Study (NPHS‐II). A second cohort, Whitehall II study (WH‐II, n = 4055), was used for replication analysis of FVIIc levels and CHD risk. Results: In NPHS‐II the minor alleles of three SNPs (rs555212, rs762635 and rs510317; haplotype H2) were associated with higher levels of FVIIag, FVIIc and FVIIa, whereas the minor allele for two SNPs (I/D323 and rs6046; haplotype H5) was associated with lower levels. Adjusted for classic risk factors, H2 carriers had a CHD hazard ratio of 1.34 [95% confidence interval (CI): 1.12–1.59; independent of FVIIc], whereas H5 carriers had a CHD risk of 1.29 (95% CI: 1.01–1.56; not independent of FVIIc) and significantly lower CAMs. Effects of haplotypes on FVIIc levels were replicated in WH‐II, as was the association of H5 with higher CHD risk [pooled‐estimate odds ratio (OR) 1.16 (1.00–1.36), P = 0.05], but surprisingly, H2 exhibited a reduced risk for CHD. Conclusion: tSNPs in the F7 gene strongly influence FVII levels. The haplotype associated with low FVIIc level, with particularly reduced functional activity, was consistently associated with increased risk for CHD, whereas the haplotype associated with high FVIIc level was not.