冠状动脉粥样硬化性心脏病患者脂蛋白酯酶基因的单核苷酸多态性的初步研究

目的　探讨脂蛋白酯酶基因 (lipoprotein lipase,L PL)单核苷酸多态性 (single nucleotidepolymorphisms,SNP)与冠状动脉粥样硬化性心脏病 (简称冠心病 )的关系。方法　利用聚合酶链反应扩增110名健康人和 10 2例冠心病患者 L PL 基因第 6外显子和第 6内含子的片段 ,采用温度调控高效液相色谱技术对扩增的片段进行了筛查 ,对筛查到的杂合片段进行序列测定 ,并与正常序列进行对照分析。结果　在L PL 基因第 6内含子中发现了 3个尚未报道的 SNP(42 12 t/ c、45 0 9t/ c、45 76 a/ c)。它们的频率在被检测的冠心病患者和健康人群中存在差异 ,其中 42 12 t/ c、45 76 a/ c两组间差异显著 (P<0 .0 5 )。结论　补充了 L PL基因 SNPs的数据库信息。L PL基因 SNPs的研究可能对冠心病等复杂疾病机理的认识有重要价值     

Common genetic variants of lipoprotein lipase that relate to lipid transport in patients with premature coronary artery disease

Two common coding sequence mutations of lipoprotein lipase (serine⁴⁴⁷-ter, producing a carboxy terminal truncation; and asp⁹-asn variants) were studied in 329 Caucasian subjects, of whom 243 had angiographic features of premature atheroscelerosis (220 with coronary artery disease; 23 with coronary and peripheral artery disease). As expected, the mean levels of cholesterol, triglycperides, LDL-cholesterol, ApoB and Lp(a) were significantly higher in the arterial disease group than in the controls. HDL levels were lower in the patient group. With regard to the common mutations, plasma triglycerides and VLDL-triglycerides were lower in subjects possessing the Serine⁴⁴⁷-Ter mutation (p=0.06 and <0.05, respectively). When the lipid distributions were analysed by tertiles, the Ser⁴⁴⁷-Ter mutation was significantly less frequent in the highest tertiles for triglycerides (p<0.02), and VLDL (p<0.04). The Asp⁹-Asn substitution was significantly more frequent in the lowest tertiles for ApoAI (p=0.05). Case-control analyses of genotypic distributions between the two groups with or without arterial disease did not show any significant differences. The possible functional effects of these common mutants of lipoprotein lipase are discussed.     

The Asn9 variant of lipoprotein lipase is associated with the — 93G promoter mutation and an increased risk of coronary artery disease

Two mutations in the lipoprotein lipase (LPL) gene, a T to G transition at position −93 of the proximal promoter region and an Asp9Asn substitution in exon 2, were examined in 762 Dutch males with angiographically-diagnosed coronary artery disease (CAD) and 296 healthy normolipidemic Dutch males. The two mutations exhibited strong linkage disequilibrium (D'=0.975). A significantly higher proportion of cases (4.86%) than controls (1.37%) carried the −93G/Asn9 allele (p=0.008). In the combined sample of cases and controls, adjusted mean plasma total cholesterol (TC) levels were significantly higher in −93G/Asn9 carriers (6.20±0.13 mmol/l) than in non-carriers (5.93±0.03 mmol/l; p=0.048), while mean high-density lipoprotein cholesterol (HDL-C) levels were lower in carriers (0.88±0.03 mmol/l) than in non-carriers (0.98±0.01 mmol/l; p=0.002). There was a trend towards higher triglyceride (TG) levels in carriers (1.96±0.14 mmol/l) compared with non-carriers (1.73±0.03 mmol/l) (p=0.08). Additionally, carrier frequencies in tertiles of TC, HDL-C, TG, and LPL activity, suggested an association of the −93G/Asn9 variant with higher TC and TG levels, and with lower HDL-C and LPL activity levels. Logistic regression revealed a significant odds ratio (OR) for the combined −93G/Asn9 genotype in CAD cases relative to controls (OR: 5.36; 95% CI: 1.57–18.24), with age, body mass index (BMI), smoking, and plasma total- and HDL-cholesterol levels included in the model. In conclusion, we show that the LPL Asp9Asn mutation is in non-random association with a T→G substitution at position −93 of the proximal promoter region and that the combined −93G/Asn9 genotype predisposes to decreased HDL-C levels and an increased risk of CAD.     

The C-480T hepatic lipase polymorphism is associated with HDL-C but not with risk of coronary heart disease

High-density lipoprotein cholesterol (HDL-C) is a known predictor of coronary heart disease (CHD). Studies have shown that the C-480T polymorphism of the hepatic lipase (HL) gene is predictive of HDL-C; however, its observed relationship with the risk of CHD has been inconsistent. We analysed four biallelic polymorphisms in the HL gene in participants from three independent Western Australian populations. Samples were collected from two cross-sectional studies of 1111 and 4822 community-based subjects assessed for cardiovascular risk factors, and a third sample of 556 subjects with physician-diagnosed CHD. Genotypes were tested for association with plasma lipids and the risk of CHD. All polymorphisms were highly correlated (D' > 0.97, r(2) > 0.90); therefore, only C-480T was analysed. The -480T allele was significantly associated with an increase in HDL-C of between 0.08 and 0.16 mmol/l in all three populations (p < 0.001). No associations with other lipids were observed, nor was an association with CHD in a case-control study of males. The TT genotype was however associated with decreased risk of myocardial infarction among cases (odds ratio = 0.39, 95% confidence interval = 0.19-0.78, p = 0.008). These findings replicate those of previous studies in three independent populations and suggest that the genetic determinants of CHD are complex and cannot be entirely explained through intermediate phenotypes.     

Cholesterol ester transfer protein,apolipoprotein E and lipoprotein lipase genotypes in patients with coronary artery disease in the Turkish population

The aim of this study was to compare patients with coronary artery disease (CAD) to healthy objects, in order to explore a possible association between CAD and the variants in the gene encoding cholesterol ester transfer protein (CETP), apolipoprotein E (Apo E) and lipoprotein lipase (LPL). The relationship between CETP MspI, apo E and LPL PvuII gene polymorphisms and serum lipids were investigated in 173 patients with CAD and 111 healthy controls. The frequency of Apo epsilon4 (p < 0.05) and CETP M1 (p < 0.01) alleles were higher in the CAD group than in the control group. In the CAD group, those with the Msp M1 allele had higher levels of total cholesterol (TC) (p = 0026) and low-density lipoprotein cholesterol (LDL-C) than those with the Msp M2 allele. Subjects with an epsilon2 allele had the lowest levels of TC and LDL-C, while subjects with the epsilon4 allele had the highest. In the control group, CETP, the Msp M2 allele was associated with a higher level of high-density lipoprotein cholesterol (HDL-C) (p = 0.012) than the Msp M1 allele. The distributions of LPL genotype and allele did not differ between the CAD and control groups. The present study demonstrates that the CETP Msp1 and Apo E gene polymorphisms are associated with variations in lipids in patients with CAD and healthy controls in Turkish population.     

冠心病患者apoE基因调控序列-219(G/T)多态性及与血脂的关系

为了研究载脂蛋白E(apoE）基因调控序列－219（G／T）多态性与人类冠心病（CHD）及其血脂水平的关系，本文采用聚合酶链反应结合了限制性片段长度多态性方法。分析了108例健康人及86例冠心病患者的－219（G／T）基因型。PCR产物直接测序验下。我们发现冠心病组apoE－219（T／T）基因型频率（0．651）和T等位基因频率（0．767）分别显著高于对照组（0．444，0．653，P＜0．05）；冠心病组和对照组T／T基因型者血清总胆固醇高于G／G基因型者。这一结果提示apoE调控区基因多态性可能影响冠心病的发生。推测apoE－219（T／T）基因型是冠心病的危险因子之一。     

Vascular endothelial growth factor gene polymorphisms and coronary heart disease: a systematic review and meta-analysis

We performed this study to better elucidate the relationship between vascular endothelial growth factor (VEGF) polymorphisms and coronary heart disease (CHD). Eligible articles were searched in PubMed, Medline, Embase, Scopus and CNKI. A total of 24 studies containing 6489 CHD patients and 5664 control subjects were analyzed. Our overall and subgroup analyses suggested that rs699947 polymorphism was significantly associated with CHD susceptibility in both Caucasians and Asians, rs1570360 polymorphism was significantly associated with CHD susceptibility in Caucasians, and rs3025039 polymorphism was significantly associated with CHD susceptibility in Asians. Besides, rs3025039 polymorphism was significantly correlated with the number of affected coronary arteries, while rs699947 and rs2010963 polymorphisms were significantly correlated with poor collateral circulation in CHD patients. Overall, our findings indicate that VEGF rs699947, rs1570360, and rs3025039 polymorphisms may affect CHD susceptibility. Moreover, VEGF rs699947 and rs2010963 polymorphisms may serve as genetic biomarkers of poor collateral circulation after myocardial ischemia.     

Identification of a common variant in the lipoprotein lipase gene in a large Utah kindred ascertained for coronary heart disease: the -93G/D9N variant predisposes to low HDL-C/high triglycerides

Defects in the lipoprotein lipase (LPL) gene are associated with dyslipidemia in the general population. Several rare mutations in the gene, as well as two common coding region polymorphisms, D9N and N291S, exhibit deleterious effects on circulating lipid levels. Using a linkage-based approach, we have identified a large Utah kindred segregating the D9N variant in the LPL gene. The kindred was ascertained for premature coronary heart disease and was expanded based on familial dyslipidemia. A genomic scan identified a region of linkage including LPL, and mutation screening identified the segregating variant. In the kindred, the variant shows high penetrance for a hypoalphalipoproteinemia phenotype, but is also associated with hypertriglyceridemia and elevated insulin levels. The strength of linkage was dependent on the combination of phenotype definition and model parameters, favoring the use of a MOD score approach. Most other studies of LPL have proceeded by mutation screening of randomly chosen individuals or selected affected probands; this is the first example identifying a segregating LPL mutation using direct linkage.     

冠心病患者内皮脂肪酶基因Thr111Ile和Gly26Ser多态性与脂蛋白代谢的关系

目的: 探讨冠心病（CHD）患者内皮脂肪酶基因（LIPG）Thr111Ile和Gly26Ser 的多态性与脂蛋白代谢的关系。 方法: 438例冠状动脉造影患者，根据造影结果分为CHD组（242例）和对照组（196 例）。应用酶法测定患者的总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-c）、低密度脂蛋白胆固醇（LDL-c）水平。同时应用聚合酶链反应-限制性内切酶片段长度多态性（PCR-RELP）核苷酸分型技术检测Thr111Ile和Gly26Ser多态性，进行统计学分析。 结果: Thr111Ile在本研究人群中的基因频率分布为CC 76.7％、CT 23.3％、TT 0.0％，等位基因频率为C 88.3％、T 11.7%。CT组HDL-c水平高于CC组（P<0.05），经多因素逻辑回归分析，CT基因仍与高HDL-c水平呈显著相关（P<0.05），CHD与Thr111Ile多态性无显著相关（P>0.05）。未发现Gly26Ser基因变异。结论: 中国汉族人群中存在LIPG基因的Thr111Ile多态性。Thr111Ile多态性中的CT基因致HDL-c水平升高，但未发现其与CHD直接相关。本研究未发现Gly26Ser多态性。     

The LPL S447X cSNP is associated with decreased blood pressure and plasma triglycerides, and reduced risk of coronary artery disease

Linkage of the lipoprotein lipase (LPL) gene to blood pressure levels has been reported. The LPL S447X single nucleotide polymorphism (cSNP) has been associated with decreased triglycerides (TG), increased high density lipoprotein cholesterol, and a decreased risk of coronary artery disease (CAD), which may occur independently of its beneficial lipid changes. To investigate the relationship between LPL S447X cSNP and these parameters, we studied a cohort of individuals with familial hypercholesterolemia in whom blood pressures and information regarding the use of blood pressure lowering medications were available. Carriers of the S447X variant had decreased TG (1.21+/-0.47 vs. 1.52+/-0.67, p<0.001) and a trend towards decreased vascular disease (12.7 vs. 19.5%) compared to non-carriers. More interestingly, however, carriers of this cSNP had decreased diastolic blood pressure compared to non-carriers (78+/-10 vs. 82+/-11, p=0.002), evident in both men and women, youths and adults, with similar trends for systolic blood pressure. Furthermore, the decrease in blood pressure appeared independent of the decrease in TG (p=0.02), suggesting that the LPL protein may have a direct influence on the vascular wall. This suggests an additional mechanism whereby this variant may have protective effects, independent of changes in plasma lipid levels.     

肝脂酶基因启动子-250G/A多态性与2型糖尿病合并冠心病易感性的相关研究

目的 探讨汉族人群肝脂酶(hepatic lipase,HL)基因启动子-250G/A多态性与2型糖尿病(type 2 diabetes mellitus,T2DM)合并冠心病(coronary heart disease,CHD)的相关性.方法 采用聚合酶链反应-限制性片段长度多态性方法(polymerase chain reaction-restricted fragment length polymorphism,PCR-RFLP)检测364例T2DM+CHD组、357例T2DM组患者和356名健康对照者HL基因启动子-250G/A多态性,并分析其对脂类的影响.结果 T2DM组与对照组HL基因启动子-250G/A多态性基因型和等位基因频率差异无统计学意义(P>0.05);T2DM+CHD组GA+AA基因型频率低于对照组(0.431 vs 0.618,P=0.031);等位基因频率差异无统计学意义(P>0.05).调整混杂因素后,Spearman相关及线性回归分析,糖尿病患者(T2DM组和T2DM+CHD组),A等位基因与高密度脂蛋白胆固醇、载脂蛋白A1呈正相关;Logistic回归分析显示,A等位基因是冠心病发生的一个危险因素.结论 HL基因启动子-250G/A多态性与2型糖尿病合并冠心病的发生有关,并影响脂类代谢.     

Lp(a) phenotypes, other lipoprotein parameters, and a family history of coronary heart disease in middle-aged males

In a study of 95 presumably healthy, 40-42-year old males from Northen Sweden, the Lp(a) phenotype distribution differed between those who had, and those who did not have one or more close relatives (parent or sib) with coronary heart disease. In the former group, 60% of the males were Lp(a+), as opposed to 28% in the latter group. Thus, in the homogeneous population sample studied, analysis of the normal inherited Lp(a) variation permitted the identification of distinct subpopulations, with respect to familial occurrence of coronary heart disease. None of a series of other parameters distinguished such sub-populations. The results reported are in agreement with our previous finding of a close association between phenotype Lp(a+) and risk of contracting coronary heart disease.     

APOA5基因单核苷酸多态性与冠心病相关性研究

目的　探讨APOA5基因多态性与冠状动脉粥样硬化性心脏病 (coronaryheartdisease ,CHD)的相关性、与血脂关系及其在中国汉族人群中的分布。方法　用聚合酶链反应 限制性片段长度多态性分析APOA5与APOA4交界区域的T/C单核苷酸多态。结果　T/C单核苷酸多态位点等位基因T、C频率在CHD组和正常对照组分别为 0 .43 5、0 .5 65和 0 .3 74、0 .62 6。等位基因频率和基因型频率分布均符合Hardy Weinberg平衡定律。T/C基因多态性基因型频率 ,等位基因T、C频率在两组间差异有显著性(P <0 .0 5 ) ,且基因型CC的冠心病患者其血浆高密度脂蛋白水平显著高于其他基因型患者 (P <0 .0 1)。中国人T/C单核苷酸多态位点T、C等位基因频率与欧洲白人比较 ,差异存在非常显著性 ( 0 .3 74vs 0 .663、0 62 6vs 0 .3 3 7;P <0 .0 0 1)。结论　T/C单核苷酸多态性与CHD存在相关性 (P <0 .0 5 ) ,患者组CC基因型与血浆高密度脂蛋白水平密切相关 (P <0 .0 1)。     

脂蛋白(a)基因单核苷酸多态性与钙化性主动脉瓣疾病及冠心病的关系

目的 探讨脂蛋白(a)[Lp(a)]基因单核苷酸多态性(SNP)与钙化性主动脉瓣膜疾病(CAVD)、冠心病(CHD)的相关性。方法 前瞻性研究。纳入2018年1-12月天津市胸科医院心内科CAVD或CHD住院患者248例,根据心脏超声多普勒、冠状动脉造影或冠状动脉CT检查结果分为两组:CAVD组101例、CHD组147例;同时选取2018年3-12月天津市胸科医院体检中心排除CAVD或CHD的171位健康体检者为对照组。检测各组Lp(a)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、载脂蛋白A(ApoA)、载脂蛋白B(ApoB)等生化指标,采用SNaPshot SNP分型技术对Lp(a)基因rs7770628、rs6415084、rs10455872三个位点进行基因分型;采用二元logistic回归分析不同基因型及Lp(a)水平对钙化性主动脉瓣疾病及冠心病发病的影响,采用线性回归分析不同基因型及ApoB水平对Lp(a)水平的影响。结果 三组间比较,患者BMI和饮酒史差异均无统计学意义(P值均＞0.05),性别、年龄、吸烟史、糖尿病史、高血压病史差异均有统计学意义(P值均＜0.05)。Lp(a) 检测值在对照组、CAVD组、CHD组分别为23.6(9.4,48.6)、37.2(16.5,79.6)、46.7(21.5,104.6)nmol/L,三组间比较差异有统计学意义(H=13.337,P<0.01);LDL值各组分别为(2.74±0.80)、(3.07±0.81)、(3.14±1.18)mmol/L,三组间差异有统计学意义(F=3.662,P<0.05);HDL值各组分别为(1.24±0.93)、(1.18±0.30)、(1.09±0.33 )mmol/L,三组间比较差异有统计学意义(F=4.281,P<0.05);ApoA值各组分别为(1.42±0.25)、(1.30±0.26)、(1.26±0.26) g/L,三组间比较差异有统计学意义(F=7.339,P<0.01);ApoB检测值各组分别为0.97(0.82, 1.10)、1.04(0.87, 1.26)、1.12(0.88, 1.31)g/L,三组间比较差异有统计学意义(H=3.948,P<0.05)。Lp(a)基因rs7770628位点对照组、CAVD组、CHD组TT基因型分别为130(76.0%)、75(74.3%)、103(70.1%),CT基因型分别为36(21.1%)、23(22.8%)、40(27.2%),CC基因型分别为5(2.9%)、3(2.9%)、4(2.7%),三组间比较差异无统计学意义(F=1.718,P＞0.05);Lp(a)基因rs6415084位点对照组、CAVD组、CHD组TT基因型分别为5(2.9%)、2(2.0%)、4(2.7%),CT基因型分别为33(19.3%)、20(19.8%)、32(21.8%),CC基因型分别为133(77.8%)、79(78.2%)、111(75.5%),三组间比较差异无统计学意义(F=0.551,P＞0.05);Lp(a)基因rs10455872位点对照组、CAVD组、CHD组AA基因型分别为171(100%)、99(98.0%)、147(100%),AG基因型分别为0(0.0%)、2(2.0%)、0(0.0%),三组间比较差异无统计学意义(P=0.058)。经logistic回归分析,与对照组相比, CAVD组及CHD组的Lp(a)水平更高,其差异有统计学意义,但未发现Lp(a)基因rs7770628及rs6415084两个位点的基因分布频率的差异有统计学意义(P>0.05)。线性回归结果表明,rs7770628以及rs6415084两个基因位点的基因分布均与Lp(a)水平升高有关。rs10455872位点只有2例SNP基因型为AG,且皆出现于CAVD组。结论 Lp(a)基因rs7770628、rs6415084位点的基因分布均与Lp(a)的升高有关,Lp(a)高表达与CAVD以及CHD患病具有相关性。     

Paraoxonase-1 (PON1) promoter region polymorphisms,serum PON1 status and coronary heart disease

Introduction

Serum paraoxonase-1 (PON1) retards the oxidation of low-density lipoprotein and cell membranes and is atheroprotective. Polymorphisms in the promoter region of the PON1 gene have been shown to affect serum PON1 levels and have been related to the presence of coronary heart disease (CHD) in some studies. However, contradictory results have been reported with regard to promoter region polymorphisms and CHD presence; therefore we have re-examined the effects of the C-108T and G-909C promoter polymorphisms on PON1 levels and the presence of CHD in a large case-control study.

Material and methods

Paraoxonase-1 activity, concentration and the C-108T and G-909C polymorphisms were measured in 417 people with CHD and 282 healthy controls, in a case control study.

Results

Paraoxonase-1 activity and concentration were significantly lower in the CHD population compared to controls regardless of their C-108T and G-909C genotype (p < 0.001). Paraoxonase-1 activity was significantly different in the C-108T genotypes in both the control and CHD groups in the order TT < TC < CC (p < 0.01). Paraoxonase-1 concentration was significantly different in the CHD group only in the G-909C genotype in the order GG > GC > CC (p < 0.01). Haplotype analysis revealed no consistent patterns of PON1 activity in the CHD population; however, in the controls PON1 activity differed between haplotypes GGCC > GGTC > GGTT (p < 0.05) and GCCC > GCTC > GCTT (p < 0.02). Neither promoter polymorphism was associated with CHD presence.

Conclusions

Paraoxonase-1 status was significantly lower in people with CHD and was affected by the promoter region polymorphisms.     

Beta-blocker induced changes in the cholesterol: High-density lipoprotein cholesterol ratio and risk of coronary heart disease

Summary The lowering of blood pressure with beta-blocking drugs has had a low impact on coronary heart disease (CHD) mortality and the question has been raised whether adverse changes in plasma lipoproteins offset the benefits of blood pressure reduction. Comparison of plasma lipoprotein concentrations in hypertensive patients treated with commonly used beta-blockers with lipoprotein concentrations in patients with coronary heart disease shows that these drugs cause clinically important shifts in the cholesterol ratio [total cholesterol (TC): high-density lipoprotein cholesterol (HDLC)] and reductions in the atheroprotective lipoprotein HDLC. The magnitude of these changes is sufficient to increase the risk of heart attack two- to four-fold depending on the initial cholesterol ratio and the duration of treatment. Only beta-blockers with marked intrinsic sympathomimetic agonist activity (pindolol) or combined alpha-beta-blocking properties (Labetalol) appear free of adverse effects on plasma lipoproteins and triglycerides. Chronic treatment with other betablockers should be accompanied by cholesterol and HDLC measurements at the beginning of therapy. Plasma lipoprotein measurements at 3–6 month intervals seem mandatory in patients with cholesterol values greater than 6 mmol/l (230 mg/dl) and (TC):HDLC ratios above 5 at the start of treatment. The risk of a coronary event must be regarded as unacceptable when the cholesterol ratio exceeds a critical value of about 6. Further controlled studies are needed to evaluate the effects of beta-blockers in hypertension when administered for periods of up to a year or more. More information is required on the behaviour of lipoprotein subspecies and apoproteins. Since the changes in lipoproteins reported in studies referred to in this review may have been submaximal the risks and the benefits from beta-blocker therapy must be carefully considered.     

A single Ser259Arg mutation in the gene for lipoprotein lipase causes chylomicronemia in Moroccans of Berber ancestry

Lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of triglyceride-rich lipoproteins. Numerous LPL gene mutations have been described as a cause of familial chylomicronemia in various populations. In general, allelic heterogeneity is observed in LPL deficiency in different populations. However, a founder effect has been reported in certain populations, such as French Canadians. Although familial chylomicronemia is observed in Morocco, the molecular basis for the disease remains unknown. Here, we report two unrelated Moroccan families of Berber ancestry, ascertained independently in Holland and France. In both probands, familial chylomicronemia manifested in infancy and was complicated with acute pancreatitis at age 2 years. Both probands were homozygous for a Ser259Arg mutation, which results in the absence of LPL catalytic activity both in vivo and in vitro. In heterozygous relatives, a partial decrease in plasma LPL activity was observed, sometimes associated with combined hyperlipidemia. This mutation previously unreported in other populations segregated on an identical haplotype, rarely observed in Caucasians, in both families. Therefore, LPL deficiency is a cause of familial chylomicronemia in Morocco and may result from a founder effect in patients of Berber ancestry. Hum Mutat 10:179–185, 1997. © 1997 Wiley-Liss, Inc.     

结合珠蛋白基因1/2多态性与中国人冠心病易感性的关联研究

目的 通过分析冠心病患者及冠脉正常组中结合珠蛋白(haptoglobin,HP)基因1/2多态性分布,初步探讨HP基因1/2多态性与冠心病易感性的关系.方法 经冠脉造影确诊冠心病组189例,冠脉正常对照组242名;采用聚合酶链反应-限制性片段长度多态性技术检测所有受试者HP基因型.结果 冠心病组HP基因型分布与对照组相比差异有统计学意义(P=0.002),表现为HP2-2基因型在冠心病组的频率明显高于对照组(0.54vs.0.35,P=0.000),单因素分析显著增加冠心病的风险(OR=2.166,95%CI:1.467～3.196),HP2等位基因的频率也明显高于对照组(0.74 vs.0.61).同时,多因素Logistic回归分析表明HP2-2基因型是冠心病的独立危险因素(P=0.002;OR=2.101,95%CI:1.311～3.367).结论 HP2-2基因型与冠心病的发生相关,可能是冠心病发病的独立危险因子;HP2等位基因可能是中国人冠心病的易感基因.

Abstract：

Objective To assess the association of haptoglobin (HP)1/2 polymorphism with coronary heart disease (CHD) in Chinese Hans. Methods One hundred and eighty-nine CHD patients and 242 healthy controls confirmed with angiography were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was utilized to genotype the HP1 and HP2 alleles and genotype frequencies in cases and controls were compared. Results The frequency of HP2-2 genotype was significantly higher in CHDs than in controls (0. 54 vs. 0.35, P=0.000). The HP2-2 genotype significantly increased the risk for CHD in univariable analysis (OR= 2. 165, 95% CI: 1. 467-3. 196). Multifactor Logistic regression analysis indicated that HP2-2 genotype is an independent risk factor to CHD (P=0.002;OR=2. 101, 95% CI: 1. 311-3. 367). Similarly, the HP2 allele frequency in the CHD group was significantly higher than that in the control subjects (0.74 vs. 0. 61, P= 0. 000). Conclusion The HP2-2genotype is associated with CHD in Chinese. HP2-2 genotype may be an independent risk factor to CHD,and HP2 allele may be a genetic susceptibility factor to CHD in Chinese.     

凝血酶激活的纤溶抑制物及其编码基因多态性与冠心病的相关性研究

目的研究凝血酶激活的纤溶抑制物（TAFI）及其编码基因多态性与冠心病（CHD）之间的相关性。方法应用聚合酶链反应-限制性内切酶片段长度多态性分析技术（PCR-RFLP）对136例冠心病患者和85名健康对照者的TAFI编码基因Thr325Ile和Thr147Ala的基因多态性进行分析,同时采用酶联免疫吸附试验双抗体夹心法对所有受试者血浆TAFI的抗原及活性水平进行检测,探讨TAFI及其编码基因的基因多态性与CHD的关系。结果健康对照组和CHD组血浆TAFI的抗原与活性水平分别为（72.50±33.95）%、（21.75±13.79）μg/ml和（185.21±89.82）%、（91.29±43.48）μg/ml,两组之间的差异有统计学意义（P〈0.01）。在健康对照组和CHD组TAFI编码基因的基因多态性分布中,Thr325Ile编码基因的3种基因型和Thr147Ala编码基因的3种基因型两组之间基因型及等位基因的多态性分布频率差异无统计学意义（P〉0.05）。在Thr325Ile编码基因的3种基因型中,Thr325Thr基因型血浆TAFI的抗原水平明显高于其他两种基因型（Thr325Ile和Ile325Ile）,差异有统计学意义（Ρ〈0.01）,而后两种基因型之间差异无统计学意义（P〉0.05）;Ile325Ile基因型血浆TAFI的活性水平较其他两种基因型（Thr325Thr和Thr325Ile）低,差异有统计学意义（Ρ〈0.01）,而后两者之间的差异无统计学意义（P〉0.05）;在Thr147Ala编码基因的3种基因型（Ala147Ala、Ala147Thr和Thr147Thr）之间,血浆TAFI的抗原与活性水平的差异无统计学意义（P〉0.05）。结论 TAFI可能是CHD的危险因子;TAFI编码基因Thr325Ile的基因多态性对血浆TAFI的抗原与活性水平有一定的影响,但TAFI的两种编码基因Thr325Ile与Ala147Thr的基因多态性与CHD的发生并无明显的相关性。