髓过氧化物酶基因多态性与原发性高血压遗传易感性的研究

目的:研究髓过氧化物酶(MPO)基因多态性与原发性高血压(EH)之间的遗传易感性.方法:采用分子流行病学方法,应用聚和酶链反应检测法107例EH和97例健康对照MPO基因型,比较不同基因型之间的分布频率及95%可信区间(CI),分析MPO基因多态性与EH易感性的关系.结果:正常人群GG、GA、AA基因型频率分别为56 7%、40 2%和3 1%,EH组分别为70 1%、29 0%和0 9%.携带GG者患EH的风险是基因型为至少一个等位基因A者的1 79倍 (95%CI 1 005~3 186).结论:本研究人群MPO基因多态与EH遗传易感性相关,等位基因A对EH易感性有保护作用.     

髓过氧化物酶463G／A基因多态性与急性冠脉综合征的相关性

目的研究髓过氧化物酶基因—463bp处G／A多态位性与急性冠脉综合征（ACS）的关系。方法选择急性冠脉综合征（ACS组）136人，包括急性心肌梗死58例和不稳定型心绞痛79例，对照组62人，采用病例一对照的研究方法，采用聚合酶链反应一限制性片段长度多态性技术进行髓过氧化物酶（MPO）基因463bp处G／A多态性基因型分析。结果携带至少一个等位基因的基因型（GG＋GA）患ACS的风险是A／A的2．11倍，携带G等位基因发生ACS的风险是携带A等位基因的2．20倍。结论MPO基因多态性与ACS的易感性有相关性，G等位基因可能是ACS的危险因素。     

髓过氧化物酶基因多态性与急性白血病及急性淋巴细胞白血病易感性Meta分析

目的:通过Meta分析方法探讨髓过氧化物酶(MPO)基因与急性白血病[包括急性髓性白血病和急性淋巴细胞白血病(ALL)]及ALL易感性的关系。方法:检索截止2016年3月31日前发表的有关MPO基因位点多态性与急性白血病及ALL易感性关联的病例对照研究的文献,采用Meta分析进行统计分析。结果:共有5篇文献被纳入Meta分析中。对于ALL组,MPO-463基因AA与GG比较:OR=1.36,95%CI=0.74~2.49,P=0.33;AA+GA与GG比较,OR=1.03,95%CI=0.80~1.34,P=0.82;AA与GG+GA比较:OR=1.39,95%CI=0.76~2.53,P=0.29;A与G比较,OR=1.06,95%CI=0.86~1.31,P=0.58;GA与GG比较:OR=1.00,95%CI=0.76~1.30,P=0.97。对于急性白血病组,AA与GG比较,OR=0.83,95%CI=0.36~1.92,P=0.67;AA+GA与GG比较,OR=0.52,95%CI=0.40~0.69,P0.000 01;AA与GG+GA比较,OR=1.01,95%CI=0.49~2.50,P=0.81;A与G比较,OR=0.64,95%CI=0.51~0.80,P=0.000 1;GA与GG比较,OR=0.51,95%CI=0.39~0.67,P0.000 01。结论:Meta分析结果表明,MPO-463位点A突变基因可以有意义地降低急性白血病易感性,而目前我们尚无足够的依据证明MPO-463基因能够影响ALL易感性。     

β纤维蛋白原-455G/A基因多态性与冠心病的关系

目的 分析β纤维蛋白原（血浆纤维蛋白原B）基因启动子区－455 bp位点多态性与冠心病的关系。方法 采用聚合酶链反应限制性片长多态性分析法检测240例冠心病患者和240例正常对照者的β纤维蛋白原基因启动子区－455 bp位点多态性,并测定血浆纤维蛋白原水平。结果 （1）冠心病组GA/AA基因型及A等位基因频率（分别为45.4%和25.2%）均高于对照组（分别为26.7%和15.2%）,差异有统计学意义（P均＜0.05）;（2）冠心病组各基因型的血浆纤维蛋白原水平均高于对照组同基因型,两组携带GA基因型者的血浆纤维蛋白原水平高于同组携带GG基因型者,携带AA基因型者血浆纤维蛋白原水平高于同组携带GA基因型者,差异有统计学意义（P均＜0.05）。结论 β纤维蛋白原基因启动子区－455 bp位点多态性与冠心病有关,A等位基因是冠心病的易感危险因素,可能通过影响血浆纤维蛋白原水平与冠心病产生联系。     

MPO G-463A基因多态性与大肠癌遗传易感性的研究

目的探讨髓过氧化物酶（MPO）G-463A基因多态性与大肠癌易感性的研究。方法取103例大肠癌组织和143例癌旁正常大肠组织（对照组）的石蜡切片样本，应用聚合酶联反应（PCR）及限制性片断长度多态性（RFLP）进行检测。结果MPO基因型（GG、GA、AA）在大肠癌组的分布为47．57％、31．07％、21．35％，对照组为27．97％、37．06％、34．97％，两组间比较差异有统计学意义（P〈0．05）；禽MPOG-463A等位片段的基因型在大肠癌组中的分布为40．O％，对照组为52．55％，两组间比较差异有统计学意义（P〈0．05）。结论MPOG-463A基因多态性可能是大肠癌发病的一个基周型危险因素，MPO基因463位点的A等位基因在大肠癌组中的表达较高，可能具有对肿瘤进行早期诊断和判断预后的潜在价值。     

乙醛脱氢酶2基因 rs671多态性和新疆汉族人群原发性高血压的关联性研究

目的：探讨乙醛脱氢酶2（ALDH2）基因 rs671多态性在新疆地区汉族人群原发性高血压（EH）发病中的作用。方法应用 Taqman 技术检测了474例汉族 EH 患者和358例正常血压者 ALDH2基因 rs671多态性。结果在男性人群中,饮酒组 rs671的 GA ＋AA 基因型频率和 A 等位基因频率均明显低于不饮酒组（P ＜0．01）;EH 组 rs671的 GA ＋AA 基因型频率和 A 等位基因频率均明显低于对照组（P ＜0．01）。而在女性人群中,EH 组和对照组 rs671的 3 种基因型频率和等位基因频率的分布差异无统计学意义（P ＞0．05）。非条件 Logistic 回归分析校正年龄、体重指数、糖尿病史、饮酒史等影响因素后,在男性人群中 rs671的 GA ＋AA 基因型者患 EH 的风险低于 GG基因型者（OR ＝0．656,95％CI：0．448～0．962,P ＜0．05）,GA ＋AA 基因型者收缩压水平明显低于GG 型者（P ＜0．05）。而在男性不饮酒者和女性人群中,GA ＋AA 基因型者和 GG 基因型者血压水平比较差异无统计学意义。结论ALDH2基因 rs671多态性可能和新疆汉族男性人群 EH 的发生相关,rs671的 GA ＋AA 基因型可能是汉族男性人群 EH 的一个保护因素。     

hTERT rs2736098、rs2075786及rs2736100位点多态性与中国人群肝癌易感性的meta分析

目的研究端粒酶逆转录基因多态性与中国人群肝癌易感性的关系。方法计算机检索中国知网(CNKI)、万方、pubmed、Web of science、EMBASE等数据库有关端粒酶逆转录基因多态性与中国人群肝癌易感性相关性的研究,按照标准纳入文献,提取数据,采用RevMan5.3和stata15.1软件进行meta分析。结果共纳入7篇文献,累计病例数2 564例,对照组2 770例。meta结果显示,rs2736098位点上,携带至少一个等位基因A的个体肝癌发病风险是携带GG基因型个体的1.28倍[OR=1.28,95%CI(1.01,1.62)];携带GA或AA基因型的个体罹患肝癌的风险是携带GG基因型个体的1.25倍[OR=1.25,95%CI(1.01,1.54)]。rs2075786位点上,携带等位基因T罹患肝癌的风险是携带等位基因C个体的1.92倍[OR=1.92,95%CI(1.52,2.43)]。结论 hTERT rs2736098位点,rs2075786位点多态性与中国人群肝癌易感性有关,rs2736100位点多态性并不能增加罹患肝癌的风险。     

细胞毒T淋巴细胞抗原4基因多态性与肝癌易感性的相关性

目的探讨细胞毒T淋巴细胞抗原4(CTLA-4)基因多态性与肝癌易感性的相关性。方法选择陕西省安康市中心医院2016年1月-2018年12月收治的70例肝癌患者,另以70例健康体检者作为对照。所有患者均检测CTLA-4基因外显子49位点的基因型分布。比较2组AA、AG、GG基因型分布与等位基因A、G的基因频率。采用Spearman相关性分析基因型分布与肝癌易感性之间的相关性,并进一步进行基因频率相对风险分析。结果 2组AA、AG、GG基因型的分布存在显著差异,肝癌患者均GG基因型居多,对照组以AG基因型居多(P0.001)。肝癌组G等位基因频率为71.43%,显著高于对照组51.43%(P0.05)。CTLA-4基因多态性与肝癌易感性之间存在明显相关性(r=0.701,P=0.012),携带G等位基因会增加肝癌患病风险[OR=4.101(2.227～10.031)]。结论 CTLA-4基因的外显子49位点基因多态性与肝癌易感性存在较大相关性,携带G等位基因的肝癌患病风险相对更大。     

原发性高血压患者颈总动脉超声等临床变量与髓过氧化物酶基因变异的关系

目的:探讨原发性高血压(EH)患者颈总动脉超声等临床变量与髓过氧化物酶(MPO)基因变异的关系。方法:应用聚和酶链反应(PCR)检测EH组107例及对照组97例患者MPO基因型,比较不同基因型之间的分布频率。同时使用B型彩色多普勒超声等检测2组患者的颈总动脉超声及其他临床变量,并进行对照分析。结果:正常人群GG、GA、AA基因型频率分别为56.7%、40.2%和3.1%,EH病例组分别为70.1%、29.0%和0.9%,EH组MPO基因AA+GA基因型频率低于对照组,二者比较有差异性(P=0.047)。EH患者的颈总动脉内径、内膜厚度等临床变量的变化与MPO不同基因型相关。结论:本研究人群MPO基因多态性与EH遗传易感性相关。EH患者的颈总动脉内径、内膜厚度及各临床变量的变化与MPO基因463G/A的变异有关。     

MTHFR基因和β纤维蛋白原455G/A基因多态性与脑梗死的遗传易感性

目的探讨MTHFR基因和β纤维蛋白原455G/A(βFib 455G/A)基因多态性与脑梗死的遗传易感性。方法运用PCR-RFLP检测154例脑梗死患者(脑梗死组)和83例健康体检者(对照组)MTHFR和βFib 455G/A基因多态性,同时检测纤维蛋白原(Fib)和血浆同型半胱氨酸水平等生化指标。结果脑梗死组患者MTHFR基因的CC、CT、TT基因型频率分别为21.4%、48.1%和30.5%,对照组分别为57.8%、25.3%和16.9%,脑梗死组TT基因型相对危险性为对照组的2.16倍;脑梗死组βFib 455G/A基因GG、GA、AA基因型频率分别为51.3%、40.3%和8.4%,对照组分别为72.3%、21.7%和6.0%。与对照组比较,脑梗死组患者GA基因型和A等位基因频率明显增高(P<0.05);具有CT+AA基因型或TT+GA基因型个体易患脑梗死,相对危险性为2.7和2.2。结论MTHFR基因突变后T等位基因和βFib基因突变后的A等位基因可能是脑梗死发生的一个遗传易感基因,MTHFR基因中CC型可能是脑梗死的保护因子,MTHFR基因和βFib 455G/A基因突变间可能存在协同作用。     

The Association between Myeloperoxidase-463G/A Gene Polymorphism and Coronary Artery Disease

Objectives To study the relationship between myeloperoxidase （MPO）-463G/A polymorphisms and susceptibility to coronary artery disease （CAD） in Han people of north Anhui province. Methods The case group consisted of 79 patients who had all angiographically proven CAD were retrospectively studied. Used polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） methods to decide the genotype of all the patients. Results The frequency of AA homozygotic type in Han people of Anhui province was 1.4%. The risk of CAD for person carrying at least one A allele genotype （ GA and AA） was 0. 37 times of GG genotype. The severity of coronary artery stenosis in CAD patients carrying at least one A allele genotype was 0. 197 times of GG genotype （ P 〈 0. 05 ）. Conclusions The frequency of AA homozygotic type and MPO-463G/A polymorphism in Han people of Anhui province influenced the risk of CAD. A allele had protective function in CAD.     

Association of the G-463A myeloperoxidase gene polymorphism with renal disease in African Americans with systemic lupus erythematosus

OBJECTIVE: Myeloperoxidase (MPO) is an enzyme expressed in neutrophils that is involved in tissue damage in inflammatory renal diseases. A functional G to A single-nucleotide polymorphism (SNP) is present at position -463 of the MPO promoter region and is associated with altered MPO expression. We hypothesized that the G-463A MPO SNP is a risk factor for developing lupus nephritis (LN) due to its potential influence on the inflammatory response. METHODS: DNA from 229 patients with SLE and 277 controls from the Carolina Lupus cohort, 58 African American patients from the Sea Island Lupus Cohort, and 51 African American patients from the Lupus Multiplex Registry and Repository were genotyped by PCR. A linear regression model was used to examine relationships between the MPO genotype, case/control status, demographic characteristics, and LN. RESULTS: There was no association of MPO genotype with systemic lupus erythematosus (SLE). However, the odds of developing LN were significantly higher among those with an A allele, compared to those without, in African American cases of all 3 cohorts. When the likelihood of developing LN was compared across MPO genotypes, the risk of developing LN was significantly higher among cases with a GA genotype versus GG (OR 2.11, 95% CI 1.12 to 3.97) and even higher with AA versus GG (OR 3.52, 95% CI 1.41 to 8.77). CONCLUSION: While the G-463A MPO SNP is not a risk factor for developing SLE, the low expressing A allele is a significant risk factor for developing LN that is gene dosage-dependent in African Americans.     

髓过氧化物酶和过氧化氢酶基因多态性及其酶活力与燃煤污染型地方性砷中毒关系的探讨

目的 了解燃煤污染型地方性砷中毒患者体内髓过氧化物酶(MPO)基因和过氧化氢酶(CAT)基因的多态性及其酶活力,分析其与砷中毒发生的关系.方法 以贵州省兴仁县交乐村燃煤污染型地方性砷中毒病区的130例砷中毒患者为病例(砷中毒)组,以居住在距病区约13 km非砷污染大果垛村的140例健康居民为对照组.采集两组人群静脉血,采用PCR-限制性片段长度多态性(PCR-RFLP)方法检测MPO基因-463 G/A位点和CAT基因-262C/T位点的多态性;采用紫外分光光度法检测MPO活力;采用比色法检测CAT活力.结果 砷中毒组MPO-463G/A位点GG、GA和AA基因型分布频率为47.24%(60/127)、44.09%(56/127)和8.67%(11/127),对照组为42.34%(58/137)、48.17%(66/137)和9.49%(13/137),两组比较差异无统计学意义(χ2=0.642,P>0.05).砷中毒组CAT-262C/T位点CC、CT和TT基因型分布频率为65.60%(82/125)、28.80%(36/125)和5.60%(7/125),对照组为76.51%(101/132)、18.94%(25/132)和4.55%(6/132),两组比较差异无统计学意义(χ2=3.845,P>0.05).未发现MPO-463G/A位点和CAT-262C/T位点多态性与砷中毒发病风险(比值比,OR)的关联度有统计学意义(MPO:Oradj=1.36,95%CI:0.74～2.50;CAT:Oradj=1.35,95%CI:0.69～2.63).砷中毒组MPO和CAT活力分别为(25.30±8.70)U/L和(2.80±1.09)×103U/L,对照组分别为(22.76±7.59)U/L和(3.90±1.01)×103U/L,两组比较差异有统计学意义(F值分别为0.760、0.855,P均<0.05).MPO-463G/A和CAT-262C/T不同基因型个体MPO和CAT酶活力比较,差异无统计学意义(F值分别为1.312、2.822,0.151、0.036,P均>0.05).结论 未发现MPO基因-463G/A位点和CAT基因-262C/T位点多态性与燃煤污染型地方性砷中毒的发病风险有关;砷可致MPO和CAT酶活力改变,此改变可能不受MPO-463G/A和CAT-262C/T多态性的影响.     

GG genotype of cyclin D1 G870A polymorphism is associated with non-cardiac gastric cancer in a high-risk region of China

Objective. Cyclin D1 (CCND1) is a regulatory protein involved in the cell cycle of both normal and neoplastic cells. Polymorphism of this gene at codon 242 in exon 4 (A870G) has an impact on the risk of several human cancers. The purpose of this study was to study the relation between the CCND1 A870G gene polymorphism and the risk of non-cardiac gastric cancer in a Chinese population. Material and methods. The study population consisted of 159 patients with non-cardiac gastric cancer and 162 cancer-free controls. CCND1 870A/G polymorphism was genotyped by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and sequencing. Results. CCND1 genotype distribution among the patients was significantly different from that among controls; AA (odds ratio (OR)=0.348, 95% CI: 0.163–0.742) and GA (OR=0.715, 95% CI: 0.506–1.012) genotypes were significantly lower in the gastric cancer patients than in the controls when subjects with the GG genotype served as the reference category. In other words, the risk of gastric cancer for subjects with the GG genotype was 2.8 times that of subjects with the AA genotype, and 1.4 times that of subjects with the GA genotype. Furthermore, in the stratification analyses, the risk of GG genotype was more evident in subjects ≥60 years of age and those positive for Helicobacter pylori (H. pylori) infection. Conclusions. The CCND1870 GG genotype is associated with an increased risk for non-cardiac gastric cancer in patients in a high-risk area of China. Larger studies with multiple polymorphisms are needed to verify this finding and the function of this polymorphism needs to be further investigated.     

细胞周期素D1基因多态性与胃癌关系的研究

目的 研究与肿瘤发生有关的细胞周期蛋白D1(CCND1)870A/G基因多态性与胃癌易感性的关系.方法 收集106例胃癌病例(包括胃体癌及胃窦癌)和108例非溃疡性消化不良患者的外周血白细胞,采用病例对照分子流行病学研究方法 ,以聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,进行CCND1基因型检测.结果 在病例组和对照组中CCND1 870位点野生型GG频率分别为19.8%和7.4%,携带AA基因型个体发生胃癌危险是携带GG型个体的0.28倍(P＜0.05,OR=0.281),即GG型个体更易感胃癌.分层分析表明,携带GG基因型个体分别在男性、年龄≥60岁及幽门螺杆菌感染亚组中患胃癌风险更高.结论 在中国胃癌高发区西安,CCND1 870A/G位点GG基因型人群更易感胃癌.     

白细胞介素-17F A7488G多态性与广东地区胃癌的关系

目的 分析白细胞介素(IL)-17F A7488G(p.His161Arg)多态性与广东地区胃癌遗传易感性及其与胃癌患者临床病理学特征和预后的关系.方法 采用聚合酶链反应-跟制性片段长度多态性(PCR-RFLP)法分析927例胃癌患者及777名健康对照者的IL-17F A7488G多态性,采用Logistic回归法和Cox比例风险法研究其对不同临床病理学特征的胃癌发病风险的影响并进行生存分析.结果 IL-17F A7488G基因型频率在胃癌患者与健康对照人群间差异有统计学意义(X2=16.55,P<0.01).与AA纯合子相比,IL-17F A7488G杂合变异基因型(GA)及纯合变异基因型(GG)显著增加胃癌的发病风险,OR值分别为1.51和1.61(95%CI分别为1.22～1.87和1.03～2.51,P值均<0.01).与AA携带者相比,携带G(GA或GG)等位基因者发生胃癌的风险显著增加(OR=1.53,95%CI:1.25～1.87,P<0.01).按临床病理特征行分层分析显示,IL-17F A7488GGA基因型与肠型、低中分化、非贲门癌、淋巴结转移等的发病风险增加有关.IL-17F A7488G不同基因型患者间生存率差异无统计学意义(P=0.534).结论 广东地区IL-17F A7488G多态性与胃癌易感性有关,IL-17F A7488G变异基因型增加胃癌的发病风险,但不是影响胃癌患者预后的危险因素.     

A Functional Polymorphism in the Interleukin-1 Receptor-1 Gene Is Associated with Increased Risk of Helicobacter pylori Infection but Not with Gastric Cancer

The proinflammatory cytokine interleukin-1 has been implicated in host susceptibility to Helicobacter pylori-associated disease. Recent studies suggest that this susceptibility may be under genetic control. It remains to be determined whether the relationship between IL-1 gene polymorphism and gastrointestinal disease in patients with H. pylori infection is due to the role of IL-1 in determining susceptibility to H. pylori infection per se or to the development of distinct pathological lesions. The aim of this study was to prospectively investigate the relationship between selected polymorphisms in three of the major IL-1 gene family members, seeking associations with H. pylori infection and/or gastric cancer. A total of 559 individuals were studied: 191 patients attending for gastroscopy, 98 with current or previous H. pylori, an additional 79 patients with gastric cancer, and 289 healthy controls. The major novel finding of the study was a marked difference in the genotype frequencies for the IL1R1 Hinfl SNP in those with current or previous evidence of H. pylori compared to those without. (GG, 53 vs 75%; GA, 40 vs 19%; AA, 7 vs 6%; P = 0.0079). The association indicates an increased risk of H. pylori infection or persistence in those with the IL1R1 Hinfl A allele (0.27 vs 0.156; P = 0.009; OR = 2.01). Our results suggest that the relationship among IL-1 gene polymorphism, H. pylori, and disease is more complex than initially proposed. More detailed studies of the IL-1 gene cluster are needed.     

Association between FGFR4 gene polymorphism and high-risk HPV infection cervical cancer

Objective: To discuss the association between FGFR4 gene polymorphism rs351855(Glu388Aly) and the susceptibility and chemotherapeutic effect of cervical cancer infected by high-risk type HPV. Methods: A total of 162 patients with high-risk HPV cervical cancer and 162 healthy women were collected and the genotypes of the FGFR4 rs351855 locus were detected. The genotype distributions in the two groups were compared. The cervical cancer patients were divided into four groups which namely good therapeutic effect group and bad therapeutic effect, recurrence or metastasis and no recurrence or metastasis group respectively, and the risks of different genotype on the curative effect and prognosis were analyzed by Logistic regression. The survival time of patients with different genotypes was compared. Results: There was no statistic difference in FGFR4 rs351855 genotype distribution between the patients group and control group(P0.05), among which the risk of chemotherapy failure on GA+AA patients was 3.257 times as much as that of the GG patients, and the risk of recurrence or metastasis of GA+AA patients was 2.783 times as much as that of the GG patients. For AA patients, the risk of chemotherapy failure and the risk of relapse and metastasis are 3.833 and 3.406 times, respectively, as much as that that of the GG patients. The overall survival of GA and AA patients was shorter than that of the GG patients, and significant difference was found(x~2=7.098, P=0.029). The difference in overall survival between GA+AA patients and GG patients was almost statistically significant(x~2=3.634, P=0.057). Conclusions: The FGFR4 rs351855 polymorphism is not associated with the susceptibility of high-risk HPV cervical cancer, but patients with gene A was at higher risk of unfavourable chemotherapy prognosis compared with patients with GG.