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.     

乌鲁木齐地区维汉两民族中冠心病患者糖蛋白IIIa基因多态性研究(英文)

Adhesionandaggregationofplateletplayacentralroleinphysi-ologicandpathologicthrombusformation.Theplateletmembranere-ceptorglycoprotein(GP)IIb/IIIaiscentraltotheseprocessesatamolecularlevel,bindingvonWillebrandfactor,whichisresponsibleforplateletadhesiontoabnormalendothelium,andfibrinogen,abivalentproteincross-linkingplateletsandcausingplateletaggregation犤1犦.Plateletaggregationisparticularlyactiveatsitesoferodedorrupturedcoronaryatheroscleroticplaquesthatunderlieunstableanginaandmyocardiali…     

中国汉族人血小板反应素蛋白1基因单核苷酸多态性与冠心病的关联研究

目的 探讨血小板反应素蛋白1(TSP-1)基因第13外显子单核苷酸多态性(SNPs),致TSP-1蛋白第700位氨基酸丝氨酸转换为天冬氨酸(700N→S)与中国汉族人冠心病有无相关性.方法 应用聚合酶链反应-限制性片断长度多态性技术(PCR-RFLP),筛查南京医科大学第一附属医院和上海中医药大学附属岳阳医院2003年11月至2007年5月437例汉族冠心病患者和对照组423例TSP-1基因第13外显子钙,结合活性片段8831A→G,对筛查到含有突变的片段进行序列测定,并与正常序列进行对照分析.结果 2组均以AA型为主,测序仅检测到AG杂合型19例,未检测到GG纯合子.在2组中AG杂合型所占比例比较差异无统计学意义(2.5%比1.9%,P＞0.05).TSP-1基因8831A→G在中国汉族人中发生频率低,与汉族人冠心病发生无相关性(AG对AA:OR=1.699;95%CI 0.309～9.348,P＞0.05).结论 TSP-1基因8831A→G不是中国汉族人冠心痛发生的独立危险因素.     

乌鲁木齐地区维汉两民族中冠心病患者糖蛋白Ⅲa基因多态性研究

Objective To determine whether a variant(PlA2) of the membrane glycoprotein IIIa(GP IIIa) gene is associated with CAD. Furthermore,the association of the polymorphism with the classical risk factors was analyzed.Methods Blood was drawn from 105 patients (pt) and 56 controls, some of those undergoing angiography. A 266 base pair fragment of the GP IIIa gene was amplified by the polymerase chain reaction(PCR) and digested with the MspI restriction enzyme. Genotypes were identified after electrophoresis of digestion products in 2.0% agarose gel. Results Of the 105 patients(pt), 65 had acute (n=19) or previous MI,20 had unstable angina (UAP), and 20 had stable angina(SAP).The PlA2 allele was carried by 0% of CAD pt versus 1.8% of Non CAD control subjects in Chinese Urumqi Uygur and Han population. The PlA2 allele was carried by 0% of CAD pt versus 7.7% of Non CAD control subjects in Uygur population.The PlA2 allele was found in 0% of CAD pt versus 0% of Non CAD control subjects in Han population.Conclusions The PlA2 variant of the gene GP IIIa is not associated with CAD in Uygur population and Han population in Urumqi city of Xinjiang Uygur Autonomous Region.     

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。     

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.     

驱动蛋白分子6基因rs20455位点基因多态性与江苏地区汉族人冠心病的相关性研究

摘要：目的：观察江苏地区汉族人群驱动蛋白分子6（KIF6）rs20455位点基因多态性与冠心病（CHD）的关系。 方法：用聚合酶链反应-限制性片段长度多态性技术（PCR-RFLP）分别检测556例冠心病患者和322例体检健康者KIF6 rs20455基因型,计算等位基因分布频率;用全自动生化分析仪检测研究对象血脂、血糖水平。 结果：冠心病组和健康人对照组KIF6基因 rs20455位点TT、TC、CC基因型频率分别为0.291、0.507、0.201和0.323、0.450、0.227（χ²=2.647,P=0.266）;T、C等位基因频率分别为0.545、0.455和0.548、0.452（χ²=0.017,P=0.898）。Logistic回归分析显示,C等位基因不是发生CHD的危险因素（OR=0.862,P=0.326,95%CI为0.641~1.160）,年龄、高血压、LDL-C和HbA1c是冠心病发生的主要危险因素（OR分别为1.079、6.239、4.734、11.128,P均＜0.05）。 结论: KIF6 rs20455位点基因多态性与江苏地区汉族人群CHD的发生无关。     

我国汉族人群MEF2A基因多态性位点的检测及其与冠状动脉粥样硬化心脏病相关性的研究

目的检测我国汉族人群中MEF2A基因存在的多态性位点，调查这些多态性位点与冠状动脉粥样硬化性心脏病发生的相关性。方法用单链构象多态性和（或）聚合酶链反应产物直接测序法对257例冠状动脉粥样硬化性心脏病阳性病例、157例冠状动脉粥样硬化性心脏病阴性对照及242名健康体检者MEF2A基因的编码区和5′非翻译区进行全基因扫描、发现多态性位点，明确多态性各位点的等位基因频率和基因型频率，研究不同基因型与冠状动脉粥样硬化性心脏病发生的相关性。结果在MEF2A基因的编码区中共筛查到4处基因多态性位点，其中3处为单核苷酸多态性位点（891C／T，1305G／A，1353G／T），1处为三联核苷酸缺失多态性位点（1294～1296CCG／-）。经病例一对照研究显示，891C／T位点TT基因型频率在病例组和对照组分别为8．2％和3．9％，经统计学检验差异无统计学意义（P=0．088）。其余3个位点的等位基因频率和基因型频率在病例组和对照组之间分布相近，差异无统计学意义（P〉0．05）。结论MEF2A基因的4个多态性位点（891C／T，1305G／A，1353G／T，1294-1296CCG／-）与我国汉族人群中冠状动脉粥样硬化性心脏病的发生无显著相关性。     

Lipoprotein lipase gene polymorphisms in Croatian patients with coronary artery disease.

Modifications in lipoprotein lipase levels lead to elevated triglycerides and reduced high density lipoprotein (HDL), both of which are risk factors for coronary artery disease (CAD). Hence, we examined the influence of the -93T/G, D9N, N291S, and S447X polymorphisms in the lipoprotein lipase (LPL) gene on CAD risk and lipid levels in Croatian patients with and without angiographically confirmed CAD. The N291S polymorphism was significantly associated with CAD (OR = 0.36; 95% CI = 0.13, 0.99; p = 0.048). This association was only moderately affected by adjusting for various lipids (OR = 0.36; 95% CI = 0.12, 1.08; p = 0.068). HDL2-cholesterol and apolipoprotein A-I levels were significantly higher in non-carriers of the -93T/G and D9N polymorphisms in the CAD group (p = 0.017 and 0.028, respectively). The N291S genetic variant did not show any significant difference between carriers and non-carriers in either group studied for any of the lipids. Lower triglyceride and higher HDL2-cholesterol levels in the control group were associated with carriers of the S447X mutation (p = 0.043 and 0.056, respectively). LPL gene polymorphisms might be involved in predisposition to CAD and determination of lipid profiles.     

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。     

ABCG1基因启动子区多态性与中国南方汉族人群冠心病多支血管病变的相关性

目的：探讨中国南方汉族人群三磷酸腺苷结合盒转运体G1（ ATP binding cassette transporter G1, ABCG1）基因启动子区单核苷酸多态性与冠心病（ coronary artery disease , CAD）的相关性。方法采用病例对照研究,采用单碱基引物延伸的多重PCR法检测482例冠状动脉造影证实的CAD患者和513例对照者的ABCG1基因启动子区域rs1378577位点A／C多态性,分析该位点多态性与中国南方汉族人群CAD易感性和病变血管数的关系。结果 rs1378577 A／C等位基因和基因型频率在CAD组和对照组之间的分布比较差异无统计学意义（ P＞0.05）;校正了性别、年龄、吸烟状况、高血压、高脂血症、糖尿病等危险因素后, rs1378577 A／C基因多态性与CAD无相关性（ P＞0.05）;rs1378577 A／C多态性在CAD单支病变和多支病变之间的分布比较差异无统计学意义（ P＞0.05）;逻辑回归分析显示,以AA vs AC＋CC分析时rs1378577 A／C多态性可能与冠状动脉病变血管数相关（OR 0.724,95％CI 0.526～0.995,P＝0.047）。结论 ABCG1基因启动子区rs1378577位点A／C多态性可能与中国南方汉族人群冠心病多支血管病变相关。     

Genetic variant in visfatin gene promoter is associated with decreased risk of coronary artery disease in a Chinese population

BackgroundVisfatin is a newly identified pro-inflammatory adipokine expressed predominantly in visceral fat. Previous studies have suggested a role for visfatin in low-grade inflammation and regulation of lipid metabolism. Most recently, a genetic polymorphism ? 1535C > T located in the visfatin gene promoter has been identified, and suggested to be associated with the regulation of visfatin expression, lipid levels. However, it is unclear whether this polymorphism has a linkage with CAD.MethodsWe conducted a hospital-based case-control study with 257 CAD patients and 292 controls to examine the potential association of the Visfatin ? 1535C > T polymorphism with CAD.ResultsThe frequencies of the CC, CT, and TT genotypes in cases were significantly different from those of controls (χ² = 6.223, P = 0.045). Subjects with the variant genotypes (CT + TT) had a 40% decreased risk of CAD relative to CC carriers (adjusted OR = 0.60, 95%CI = 0.40–0.89). Furthermore, the adjusted OR of a TT genotype for CAD was 0.52 (95%CI = 0.31–0.87). There was a significant association between Visfatin ? 1535C > T polymorphism and triglyceride levels in both CAD patients and controls (P = 0.003, 0.018, respectively). In stratified analyses, the T allele was significantly associated with reduced risk of CAD in males, subjects with age < 59 years, and non-smokers. Moreover, a borderline statistical significance (P = 0.058 for trend) was observed between the variant genotypes and severity of CAD.ConclusionOur results suggested that Visfatin ? 1535C > T polymorphism might be associated with reduced risk of CAD in a Chinese population.     

Periostin基因多态性与苏皖汉族人群冠心病发病的初步研究

目的研究Periostin（POSTN）基因多态性与苏皖汉族人群冠心病发病的关系。方法采用聚合酶链反应一限制性片段长度多态法检测POSTN基因启动子区位点（SNPA-953T）基因型。观察POSTN基因突变率与冠心病发病的可能关系。结果证实在中国人群POSTNA一953T存在1Tr基因型。冠心病患者基因型分布：POSTNA-953T（AA型275例,AT型202例,TT型16例）。正常人群基因型分布：POSTNA-953T（AA型368例,AT型266例,TT型31例）。POSTN基因型分布冠心病组与正常人群间差异无显著性意义。结论POSTN基因多态性与冠心病发病危险未发现明显相关。     

Gender-specific effect of estrogen receptor-1 gene polymorphisms in coronary artery disease and its angiographic severity in Chinese population

BACKGROUND: The role of common polymorphisms of the estrogen receptor-1 in coronary artery disease (CAD) and it association with angiographic severity reminds conflicting in sexes and different races. METHODS: Two-hundred ten angiographically defined Chinese CAD patients and 174 control subjects were enrolled. DNA was obtained and the polymorphisms were analyzed by the polymerase chain reaction. The region containing the PvuII T/C and the XbaI A/G sites was amplified. PCR product was cleaved with the restriction endonucleases. RESULTS: No significant differences in PvuII and XbaI genotype and allele frequencies were noted between the CAD and controls.However, when stratified by gender, we noticed the PvuII genotype and allele frequencies were significantly different between CAD and controls, but in male group only, not in female group. Diabetes, hypertension, high LDL levels and the PvuII CC genotype were independent risk factors for CAD. PvuII CC was associated with the angiographic severity of CAD measuring by the number of diseased vessels as well. For XbaI, no association was found with the CAD susceptibility before and after gender stratification. CONCLUSION: This study revealed a gender-specific effect of PvuII polymorphism in Chinese CAD subjects. PvuII gene polymorphisms affect CAD susceptibility in man only. The PvuII CC is a risk factor for CAD and it is associated with angiographic CAD severity.     

Thrombospondin-4 A387P polymorphism is not associated with coronary artery disease and myocardial infarction in the Chinese Han population

Recently, conflicting data have been reported regarding the possible contribution of the TSP-4 (thrombospondin-4) A387P polymorphism to CAD (coronary artery disease) or MI (myocardial infarction). To investigate a possible association between the A387P polymorphism and CAD or MI in the Chinese Han population, we conducted a case-controlled study including 817 patients with angiographically verified CAD or those who survived an acute MI and 847 control subjects. The TSP-4 A387P polymorphism was determined by PCR and PCR-RFLP (restriction-fragment-length polymorphism) analysis. The prevalence of the 387P allele was 3.8% in the healthy controls, which was less frequent than those in Western populations (19.6-23.2%). No association of the A387P polymorphism with an altered risk of CAD, MI or premature MI was found in our present study (CG+CC compared with GG, P (CAD)=0.51, P (MI)=0.13, P (Premature MI)=0.17 respectively). We concluded that a relationship between the TSP-4 A387P polymorphism and CAD or MI was unlikely in our population. Additional investigations should be performed in populations at different risk of coronary events in order to elucidate further the possible contribution of this polymorphism to cardiovascular disease.     

血管紧张素系统基因多态性与早发冠心病的相关性研究

目的探讨血管紧张素转换酶（ACE）和血管紧张素Ⅱ1型受体（AT1R）基因多态性与早发冠心病（CAD）的关系。方法用PCR法检测41例早发CAD和64例迟发CAD患者体细胞ACE基因插入／缺失（I／D）多态性和AT1R-A1166C基因多态性，并与50例健康者对照。结果105例CAD患者ACE的DD基因频率分布与对照组比较差异有显著性（P〈0．05）；早发和迟发CAD患者与对照组比较，D等位基因和DD基因频率显著高于对照组（P〈0．05）。早发CAD组AT1R的CC基因型和C等位基因频率与对照组相比差异有显著性（P=0．036，P=0．008）。联合基因多态分析，早发CAD合并ACE-DD＋AT1 R—CC基因型频率显著高于对照组（P=0．036）；迟发CAD合并ACE-DD＋AT1 R—CC基因型频率与对照组比较差异无显著性（P=0．206）。结论早发CAD组与ACE的DD基因频率和ATIR的A1166C基因频率分布相关，ACE-DD基因频率与AT1R—CC基因频率在早发CAD的发病中具有协同作用。     

Association of polymorphisms in the ALOX15B gene with coronary artery disease

Background

Atherosclerosis is a multifactorial disease and the underlying cause of coronary artery disease (CAD), myocardial infarction and stroke. Two main features are involved in the progression of atherosclerosis, lipid retention and inflammation. 12/15-lipoxygenases are involved in inflammation and have been implicated in atherosclerosis. Genetic association studies of the 15-lipoxygenase 1 (ALOX15) in humans revealed a neutral to atheroprotective role of the enzyme. Recently the epidermis-type 15-lipoxygenase 2 (ALOX15B) has been identified in human atherosclerotic plaques but its role in human atherosclerosis is still unclear.

Methods

We screened the ALOX15B gene for polymorphisms and investigated the association of 18 detected polymorphisms with angiographically documented CAD in a case–control study (n = 496). In addition, we measured in vitro the enzyme activity and Michaelis–Menten kinetics of the detected non-synonymous polymorphic variants p.Arg486His (c.1457G > A), p.Gln656Arg (c.1967A > G) and p.Ile676Val (c.2026A > G).

Results

We found that the linked polymorphisms at position c.1458-38G > C, c.1579 + 71C > T and c.1656G > A are associated with CAD (OR: 0.51 (0.27–0.94), p-value: 0.03). In addition, we show that the activity and the kinetics of the three non-synonymous ALOX15B enzyme variants (p.Arg486His, p.Gln656Arg and p.Ile676Val) are similar to the wild-type enzyme.

Conclusions

Our data indicate that the ALOX15B gene may be associated with coronary artery disease. However, larger studies would be necessary to confirm the association of these polymorphisms with CAD. In contrast, our study did not find frequent non-synonymous polymorphisms in ALOX15B altering enzyme activity in Europeans.     

Interleukin-33 gene polymorphisms and chronic obstructive pulmonary disease in the Chinese Han population

ObjectiveTo investigate the relationship between interleukin (IL)-33 gene polymorphisms rs928413 and rs7044343 with chronic obstructive pulmonary disease (COPD) in the Chinese Han population.MethodWe assessed IL-33 rs928413 and rs7044343 polymorphisms by Sanger sequencing of PCR products amplified from the genomic DNA of 160 COPD patients and 123 healthy controls.ResultsThere was no significant difference in the distribution of rs928413 AA, AG, or AA genotypes or rs7044343 CC, CT, or TT genotypes between the two groups. However, COPD patients had a significantly higher frequency of the rs928413 G allele G (14.1% vs 7.3%, respectively). This allele was significantly associated with susceptibility to COPD (odds ratio [OR]: 2.04, 95% confidence interval [CI]: 1.12–3.57). The rs928413 dominant inheritance model was associated with COPD susceptibility (OR: 2.08, 95%CI: 1.09–4.04).ConclusionThe G allele of rs928413 and the rs928413 dominant inheritance model were associated with susceptibility to COPD in the Chinese Han population.