南京及周边地区冠心病患者CYP2C19基因多态性分析

目的 探讨南京及周边地区冠心病患者CYP2C19基因多态性的相关分布,分析性别和年龄与CYP2C19基因多态性的关系.方法 选取2015年5月至2016年4月期间在南京市第一医院拟使用氯吡格雷抗血小板治疗的冠心病患者共2997例.男性1963例,女性1034例;患者平均年龄66.3±11.4岁,＜65岁患者1284例,≥65岁患者1713例.采用“等位基因特异PCR”结合荧光探针技术检测CYP2C19基因多态性,并分别统计不同性别和不同年龄与基因多态性发生频率的关系.结果 本研究共检测到CYP2C19六种基因型:CYP2C19*1/*1,*1/*2,*1/*3,*2/*2,*2/*3,*3/*3,其基因频率分别为38.5％、41.1％、6.3％、11.1％、2.7％、0.3％,共对应三种代谢表型:快代谢型(*1/*1),占38.5％;中间代谢型(*1/*2、*1/*3),占47.4％;慢代谢型(*2/*2、*2/*3、*3/*3),占14.1％.等位基因CYP2C19*1、CYP2C19*2、CYP2C19*3的频率分别为62.2％、33.0％和4.8％.不同性别和不同年龄基因多态性差异无统计学意义.结论 南京及周边地区冠心病患者CYP2C19基因多态性分布与中国其他地区人群研究结果基本一致,与性别和年龄无相关性.     

CYP2C19基因多态性影响颈动脉血管内支架置入术后氯吡格雷疗效

目的:分析CYP2C19基因多态性对氯吡格雷治疗颈动脉血管内支架置入术(CAS)后患者氯吡格雷抵抗和支架内血栓形成的影响。方法:2014-10—2015-10在本院神经内科诊治的缺血性脑血管病需行CAS治疗的80例患者为研究对象。检测所有患者CYP2C19基因型,分析不同基因型患者所占比率,以及CYP2C19基因发生无功能突变(*2、*3)患者术后经氯吡格雷治疗3个月内氯吡格雷抵抗(CR)发生率和支架内血栓形成发生率的情况。结果:80例患者CYP2C19基因检测结果显示,*1/*2基因型所占比率最高,为37.50%,其次为*1/*1基因型(31.25%)。CYP2C19基因无功能突变(*2、*3)所占比率为68.75%,携带一个无功能突变基因(*1/*2、*1/*3)所占比率为45.00%,同时携带2个无功能突变基因(*2/*2、*2/*3、*3/*3)所占比率为23.75%。术后3个月后CR总发生率为25.00%,支架内血栓形成发生率为16.25%。CYP2C19*2基因携带者(*1/*2、*2/*2)CR发生率和支架内血栓形成发生率均高于CYP2C19*3基因携带者(*1/*3、*3/*3)(P0.01)。结论:CYP2C19*2基因是影响CAS术后患者CR发生和支架内血栓形成的重要因素,影响患者预后。     

福建汉族氯吡格雷药物代谢相关基因CYP2C19的多态性分布研究

目的 探讨中国福建汉族人群与氯吡格雷代谢相关的CYP2C19基因多态性的分布.方法 采用聚合酶链反应-限制性片段长度多态性检测以及直接测序对1001名无亲缘关系的福建汉族志愿者进行CYP2C19*2、CYP2C19*3以及CYP2C19* 17基因型的检测.结果 在全部对象中,CYP2C19*2、*3和*17的频率分别为32.4％、5.8％和0.4％.根据CYP2C19基因多态位点功能代谢分型,携带CYP2C19*2或*3的中间代谢型(*1/*2和*1/*3)与弱代谢型(*2/*2和*2/*3)分别占47.95％和13.99％.该结果与日本、韩国、新加坡、马来西亚、泰国人群及中国的傣族、蒙古族、黎族和回族相似(P＞0.05),但是与中国的哈萨克族及维吾尔族,以及伊朗、俄罗斯、意大利、波兰、挪威、加拿大印第安人、玻利维亚、埃及、坦桑尼亚等国家的人种差异有统计学意义(P＜0.05).结论 氯吡格雷药物代谢相关基因CYP2C19的分布存在种族(地区)差异.该多态在中国福建汉族人群中的分布与中国傣族、蒙古族、黎族、回族及部分东亚、东南亚人群无明显差异,但与中国哈萨克族和维吾尔族以及部分欧洲、南美洲和非洲人群相比有较多的中间代谢型及弱代谢型(P＜0.05).     

北京地区冠心病患者CYP2C19基因多态性检测

目的分析北京地区冠状动脉粥样硬化性心脏病(简称冠心病)患者CYP2C19基因多态性分布特点,探讨性别和年龄与CYP2C19基因多态性的关系。方法收集2017年4月至2018年3月于我院心脏内科就诊需服用氯吡格雷进行抗血小板治疗的冠心病患者260例,用实时荧光PCR方法对患者进行CYP2C19基因多态性检测,根据Hardy-Weinberg遗传平衡定律检测样本的群体代表性,计算各基因型、等位基因和代谢型分布的频率,比较年龄、性别与代谢型分布的相关性。结果 260例冠心病患者中,野生型纯合子CYP2C19*1/*1和突变杂合子*1/*2所占比例最多,分别为95例(36.55%)和103例(39.63%);等位基因*1所占比例最多(59. 80%);正常代谢型和中代谢型所占比例最多,分别为95例(36. 54%)和121例(46. 54%);不同性别、不同年龄的各基因代谢型分布差异无统计学意义。结论北京地区冠心病患者CYP2C19的基因分布与中国正常人群相似,性别、年龄与代谢型无相关性。     

北方地区汉族消化道疾病中CYP2C19基因多态性分析

目的探讨中国北方地区汉族消化道疾病患者中CYP2C19基因多态性的频率分布及其与消化道疾病的相关性。方法采用数字荧光分子探针杂交法测定1 429例北方汉族消化道疾病的CYP2C19基因型,并根据其药物代谢活性分为超快代谢(ultra-rapid metabolizer,UM)型、快代谢(extensive metabolizer,EM)型、中间代谢(intermediate metabolizer,IM)型和慢代谢(poor metabolizer,PM)型四种。结果 CYP2C19等位基因*1、*2、*3和*17的频率分别为64.3%、29.7%、4.9%和1.0%。CYP2C19 UM型患者占1.2%(17例),EM型占41.5%(593例),IM型占45.3%(647例),PM型占12.0%(172例)。幽门螺旋杆菌总体感染阳性率为75.3%,不同CYP2C19代谢型患者的感染阳性率差异无统计学意义。在非萎缩性胃炎、萎缩性胃炎、消化性溃疡、反流性食管炎、Barrett食管和胃癌等消化道疾病之间CYP2C19的代谢型分布差异无统计学意义。10例胃癌患者中有8例为IM型。结论 CYP2C19 IM型和EM型是北方地区汉族消化道疾病中常见的代谢类型,CYP2C19*2、*3及PM型的频率高于欧洲人群,而CYP2C19*17及UM型频率低于欧洲人群。     

CYP2C19、ALDH2和MTHFR基因多态性与冠心病的相关性研究

目的 探讨细胞色素P450 2C19 (cytochrome P450 2C19,CYP2C19)、乙醛脱氢酶2(acetaldehyde dehydrogenase 2,ALDH2)和亚甲基四氢叶酸还原酶(methylene tetrahydrofolate reductase,MTHFR)基因多态性与冠心病的相关性.方法 分别采用DNA微阵列芯片技术和PCR-芯片杂交方法,对187例冠心病患者和166名健康体检者的CYP2C19、ALDH2和MTHFR位点进行多态性分析.结果 CYP2C19*2/*2、ALDH2 AA和MTHFR TT基因型及频率在冠心病组分别为8.9％、12.3％和34.9％,在对照组分别为3.6％、1.8％和4.1％,两组比较,差异均具有统计学意义(P＜0.05);Logistic回归分析发现ALDH2和MTHFR基因多态性是冠心病发生的重要危险因素,ALDH2 GA和AA基因型:OR值=2.09,MTHFR CT和TT基因型:OR值=2.11.结论 ALDH2和MTHFR基因多态性可增加冠心病的发生风险.     

CYP2C19基因多态性与肺鳞癌发病的相关性

目的 探讨CYP2C19基因多态性与肺鳞癌发病的相关性.方法 选取2015年6月至2015年12月军事医学科学院附属医院收治的肺癌患者.入院后完善病例资料,检测CYP2C19基因表型,单因素及多因素分析CYP2C19基因与肺鳞癌发病的相关性,分析其是否为肺鳞癌发病的独立危险因素.结果 本研究共入组200例肺癌患者,其中肺鳞癌59例.肺鳞癌中,快代谢型患者显著多于其它类型的肺癌患者(66.10% vs.46.10%).多因素分析结果表明快代谢型患者与慢代谢型患者相比,其发生肺鳞癌的风险增大约5.9倍(OR=5.987,95%CI:1.118~3.272).结论 CYP2C19快代谢型改变是肺鳞癌发病的独立危险因素.     

细胞色素P450 2C19基因多态性与肺癌遗传易感性

目的 通过对肺癌组及对照组细胞色素P450 2C19(cytochrome P450 2C19,CYP2C19)等位基因进行基因分型,探讨CYP2C19基因中G681A和G636A多态性的分布与肺癌易感性的关系.方法 提取293例肺癌患者和300例健康对照组患者的外周血基因组DNA,用实时荧光PCR方法对CYP2C19进行基因分型.对肺癌组和健康对照组基因分布进行比较.结果 肺癌组CYP2C19* 2/*3基因型显著高于正常对照组,差异有统计学意义(18.77％ vs 5.67％;P=0.000),对照组CYP2C19* 1/*2基因型显著高于肺癌组,差异有统计学意义(30.67％ vs 13.99％;P=0.000).两组病例CYP2C19代谢型分布比较结果,肺癌组慢代谢型频率超过对照组一倍以上(33.45％ vs 15.33％).肺癌与各相关指标的多因素Logistic 相关分析结果显示,CYP2C19慢代谢型可能是肺癌发生的独立危险因素(P=0.000,OR:2.755,95％ CI:1.748 ～4.343).结论 CYP2C19慢代谢型可能与肺癌的发生有关.     

CYP2C9基因多态性与药物代谢

肝细胞色素 CYP2 C9催化一系列药物在体内的生物转化。CYP2 C9基因多态性形成的个体差异是相关药物代谢差异的主要原因 ,本文综述了 CYP2 C9基因的主要多态性类型在不同人群中的分布状况以及多态性与相关药物代谢的关系     

Genetic polymorphisms and phenotypic analysis of drug-metabolizing enzyme CYP2C19 in a Li Chinese population

CYP2C19 is a highly polymorphic gene and CYP2C19 enzyme results in broad inter-individual variability in response to certain clinical drugs, while little is known about the genetic variation of CYP2C19 in Li Chinese population. The aim of this study was to identify different CYP2C19 mutant alleles and determine their frequencies, along with genotype frequencies, in the Li Chinese population. We used DNA sequencing to investigate promoter, exons, introns, and 3’UTR of the CYP2C19 gene in 100 unrelated healthy Li individuals from Hainan Province, China. We also used SIFT and PolyPhen-2 to predict the protein function of the non-synonymous mutation in CYP2C19 coding regions. We identified 22 different CYP2C19 polymorphisms in the Li Chinese population, including three novel variants (-254A > G, 17807T > C and 58025C > T). The allele frequencies of CYP2C19*1A, *1B, *2A and *3A were 50%, 24%, 24.5%, and 1.5%, respectively. The most common genotype combinations were *1A/*1B (48%) and *1A/*2A (49%). Additionally, the mutation Ala161Pro was predicted to be intolerant and possibly damaging by SIFT and PolyPhen-2, respectively. Our results shed new light on CYP2C19 polymorphisms in Li individuals, which may help to optimize pharmacotherapy effectiveness by providing personalized medicine to this ethnic group.     

Association of CYP2C19*2 and *3 Genetic Variants with Essential Hypertension in Koreans

Purpose

The cytochrome P450 2C19 (CYP2C19) metabolizes arachidonic acid to produce epoxyicosanoid acids, which are involved in vascular tone and regulation of blood pressure. Recent findings suggest that CYP2C19 gene might be considered as a novel candidate gene for treatment of cardiovascular disease. The aim of the present study was to evaluate the association between two variants, CYP2C19^*2 (681G>A) and CYP2C19^*3 (636G>A) and the development of essential hypertension (EH) in Koreans.

Materials and Methods

We carried out an association study in a total of 1190 individuals (527 hypertensive subjects and 663 unrelated healthy controls). The CYP2C19 polymorphisms were genotyped using the SNaPShot™ assay.

Results

The distribution of alleles and genotypes of CYP2C19^*3 showed significant difference between hypertensive patients and normal controls (p=0.011 and p=0.013, respectively). Logistic regression analysis indicated that the CYP2C19^*3 (636A) allele carriers were significantly associated with EH [odds ratio, 0.691; 95% confidence interval (CI), 0.512-0.932, p=0.016], in comparison to wild type homozygotes (CYP2C19^*1/^*1). Neither genotype nor allele distribution of CYP2C19^*2 polymorphism showed significant differences between hypertensive and control groups (p>0.05).

Conclusion

Our present findings strengthen the evidence of an association between CYP2C19 gene polymorphism and EH prevalence. In particular, the CYP2C19^*3 defective allele may contribute to reduced risk for the development of EH.     

Distribution of polymorphisms in the CYP2C9 gene and CYP2C19/CYP2C9 haplotypes among Venezuelan populations

Background: Polymorphisms with decreased enzyme activity of their gene products have been reported in region CYP2C with population variations in haplotype structure.

Aim: To estimate the allelic and genotypic frequencies of variants CYP2C9*2 and CYP2C9*3 and of CYP2C9/CYP2C19 haplotypes in Venezuelan populations.

Subjects and methods: Six hundred and thirty-four individuals from nine admixed populations (AP) and the Warao indigenous group were studied. Allelic frequencies, linkage disequilibrium and genetic distances for haplotypes were calculated and compared within Venezuela and with data available in the literature.

Results: Heterogeneity in the distribution of CYP2C9 alleles and CYP2C9/CYP2C19 haplotypes among the AP and the Warao was observed. The joint frequency of haplotypes, with at least one non-functional variant, shows values in AP between 21–41%, while in Warao it reaches 5%. The haplotype that includes the Asian and rare Latin America CYP2C19*3 allele was detected in most AP and in Warao. Pairwise Fst values showed that the Warao was an outlier compared with the AP, while these are closer to European-derived populations. No significant correlation was found between haplotype frequencies and admixture.

Conclusions: These results support the need to understand the distribution of genomic biomarkers related to the metabolism of drugs, for planning national public health strategies.     

Genetic Polymorphism of CYP2C19 Gene in the Stanislas Cohort. A link with Inflammation

CYP2C19, a member of the cytochrome P450 family, metabolises arachidonic acid to produce epoxyeicosanoid acids, which are involved in vascular tone and inflammation. Thus, this study describes the possible relationship between a CYP2C19 polymorphism (681G>A) and three inflammatory markers: interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and high sensitivity C-reactive protein (hs-CRP) in healthy individuals.
In a sub-sample of 178 men and 181 women from the Stanislas study, we quantified plasma IL-6 and TNF-α concentrations by using an enzyme-linked immunosorbent assay, and serum hs-CRP concentration by immunonephelometry. The CYP2C19 681G>A polymorphism was genotyped using the kinetic thermocycling allele specific PCR method.
In the Stanislas cohort, the frequency of the allele CYP2C19*2 (681A) was 17.8%. Circulating levels of inflammatory factors were increased in individuals homozygous for the defective allele CYP2C19*2 (A) notably IL-6 in the whole sample ( P = 0.0008) and hs-CRP only in women ( P = 0.008), with a significant interaction with sex ( P = 0.005), in comparison to carriers of one copy or more of the wild type allele CYP2C19*1 (G). Only a trend of association ( P = 0.089) was found between this polymorphism and TNF-α concentration in the whole sample.
The association between CYP2C19*2 polymorphism and inflammatory markers' concentrations could suggest that CYP2C19 may be considered as a new candidate gene for cardiovascular risks via inflammation.