NR1I2基因多态性对华法林维持剂量个体差异的影响

目的探讨NR1I2相关单核苷酸多态性对华法林维持剂量个体差异的影响。方法共179名机械瓣膜置换术后患者纳入研究。NR1I2-25385C>T,NR1I2 7635G>A基因型检测采用直接测序法,VKORC1-1639 G>A,CYP2C9*3基因型检测采用PCR-RFLP法;判断患者是否入选的INR值、及华法林维持剂量均通过查阅患者定期复诊的电子病历获得;统计分析NR1I2-25385C>T,NR1I2 7635G>A的基因分布频率,及其与华法林维持剂量的相关性。结果 179名机械瓣膜置换术患者中,NR1I2-25385C>T的基因型频率分布为CC型62.6%、CT型31.3%和TT型6.1%;NR1I2 7635G>A的基因型频率分布为GG型30.7%、GA型49.2%和AA型20.1%。NR1I2-25385 C>T各基因型组的剂量分别为:CC型(3.0±1.2)mg,CT型(3.0±1.2)mg,TT型(2.8±0.8)mg;各组间的剂量无统计学差异。NR1I2 7635G>A各基因型组的剂量分别为:GG型(2.7±1.0)mg,GA型(3.1±1.1)mg,AA型(3.1±1.4)mg;GA与AA型组的华法林维持剂量显著高于GG型(P<0.05)。结论 NR1I2 7635G>A突变后与华法林维持剂量上调相关,患者在制定个体化给药方案时应参考NR1I2 7635G>A基因型。     

ABCB1基因多态性对肾移植受者环孢素血浓度的影响

目的:研究肾移植术后患者ABCB1基因多态性对环孢素（CsA）血浓度的影响。方法:采用PCR-RFLP（聚合酶链反应-限制性片段长度多态性）方法对339名服用CsA的肾移植患者进行ABCB1基因1236C>T、2677G>T/A和3435C>T多态性检测,荧光偏振免疫法检测肾移植患者CsA血浓度。结果:在339名肾移植患者中,ABCB1基因1236C>T、2677G>T/A和3435C>T突变等位基因频率分别为64.25%、51.54%和35.75%。ABCB1 1236C>T基因多态性检测显示,在移植术后1年,CC基因型个体的CsA血谷浓度明显高于CT和TT基因型个体（P<0.05）。2677G>T/A基因多态性检测提示,在移植术后7d,杂合子GA+GT基因型携带者的C₀高于GG和AA+TT+AT基因型携带者（P<0.05）。3435C>T基因多态性检测表明:在移植术后3个月,突变纯合子TT基因型携带者的C₀低于CC和CT基因型携带者（P<0.05）。其余各时间点,上述3种基因多态性对CsA血谷浓度无明显影响（P>0.05）。结论:ABCB1基因1236C>T、2677G>T/A和3435C>T多态性对极少数时间点的CsA浓度有影响,但对绝大多数时间点的环孢素浓度无影响。     

药物代谢酶和转运体基因多态性与中国癫痫患儿服用奥卡西平的活性代谢物血药浓度关联性研究

目的 研究代谢酶和转运体基因多态性对中国癫痫患儿服用奥卡西平的活性代谢物10-羟基卡马西平(monohydroxycarbazepine,MHD)血药浓度是否有显著影响。方法 前瞻性收集年龄0～14岁服用奥卡西平达稳态的谷浓度血浆样本,酶放大免疫法测定患者MHD血药浓度,双脱氧链终止法检测患儿代谢酶基因UGT2B7802T>C、UGT1A9I399C>T,以及转运体基因ABCB1 3435C>T和ABCC2 1249G>A多态性,应用单因素方差分析与Fisher最小显著差检验法分析代谢酶和转运体基因多态性与奥卡西平活性代谢物血药浓度的关联性。结果 研究共收集161例癫痫患儿的谷浓度血浆样本,单因素方差分析显示,转运体基因ABCB1 3435C>T与MHD血药浓度显著相关(P<0.05)。随后进行Fisher最小显著差检验,携带ABCB1 3435C>T突变等位基因患儿的血浆MHD浓度明显高于非携带者,未见其他代谢酶和转运体基因多态性显著影响MHD血药浓度。结论 转运体基因ABCB1 3435C>T与中国癫痫患儿奥卡西平活性代谢物血药浓度存...     

龙岩地区黄疸新生儿G6PD缺乏症基因突变类型分析

目的 探讨龙岩地区黄疸新生儿G6PD缺乏症基因突变类型。方法 选取我院新生儿科住院的黄疸患儿1 253例，对生化诊断G6PD缺乏的142例患儿采用Snapshot技术平台进行常见的12种G6PD基因突变检测。结果 142例患儿中男性135例，女性7例，均检出G6PD基因突变位点，共检出8种单一位点突变，分别是c.1376G>T(70例)、c.1388G>A(46例)、c.1024C>T(7例)、c.871G>A(5例)、c.95A>G(5例)、c.392G>T(4例)、c.1360C>T(2例)、c.487G>A(1例);2种复合突变c.1388C>A/c.1376G>T(1例)、c.1376G>T/c.871G>A(1例),其中c.1376G>T和c.1388G>A总占比81.69%。结论 龙岩地区黄疸新生儿人群G6PD缺乏症发病率较高，男性检出率显著高于女性；c.1376G>T、c.1388G>A是龙岩地区黄疸新生儿G6PD缺乏症较常见的基因突变类型。     

枣庄地区阿司匹林和氯吡格雷的基因多态性分布分析

目的：分析阿司匹林、氯吡格雷的疗效和安全性。方法：选取2021年1月—2022年12月在山东国欣颐养集团枣庄中心医院住院期间检测阿司匹林、氯吡格雷相关位点基因检测的患者,采用DNA连接酶测序法对患者血样的药物相关基因位点进行检验。结果：阿司匹林用药基因检测的675例患者中共检测5个药物相关基因位点,分别为PTGS1-842A>G、ITGB3-176T>C、PEAR1-9-3996G>A、GP1BA-482C>T、LTC4S-444A>C;氯吡格雷用药基因检测的308例患者中共检测3个药物相关基因位点,分别为CYP2C19^*2-681G>A,CYP2C19^*3-636G>A,CYP2C19^*17-806C>T。基因位点的基因频率分布均符合Hardy-Weinberg平衡定律,样本具有群体代表性。结论：阿司匹林、氯吡格雷用药基因检测可为患者精准治疗提供个体化的用药参考。     

VKORC1、CYP2C9、CYP4F2、EPHX1基因多态性对华法林剂量的影响

目的:探讨中国汉族人群VKORC1、CYP2C9、CYP4F2和EPHX1基因多态性对华法林剂量的影响。方法:采用限制性片段多态性技术和碱基淬灭探针技术检测197名心脏机械瓣膜置换术后患者的VKO RC1-1639G>A、CYP2C9 1075A>C、CYP4F2 rs2108622和EPHX1 rs2292566的基因多态性,结合患者的临床特征,分析各因素对华法林剂量的影响。结果:VKO RC1-1639G>A、CYP2C9 1075A>C、CYP4F2 rs2108622、EPHX1 rs2292566基因多态性以及体重和年龄分别解释了30.2%、7.0%、2.8%、3.6%、1.9%和1.7%的华法林个体剂量差异,多因素联合可解释46.7%的华法林个体剂量差异。结论:VKORC1-1639G>A和CYP2C9 1075A>C基因多态性是影响华法林稳定剂量重要的遗传因素;CYP4F2 rs2108622和EPHX1 rs2292566基因多态性以及年龄、体重对华法林的稳定剂量有影响,但较小。     

山西省21-羟化酶缺乏症基因型与临床表型相关性分析

目的研究山西省21-羟化酶缺乏症患儿的基因突变,探讨基因型和临床表型的相关性。方法回顾性分析2014年1月至2016年10月山西省儿童医院收治的15例21-羟化酶缺乏症患儿的临床资料,采用Sanger测序法进行CYP21A2基因突变分析。CYP21A2基因检测结果与其临床表型进行比较,分析基因型与临床表型的相关性。结果 (1)本组15例患儿均为经典型患者,其中失盐型(SW)8例,单纯男性化型(SV)7例。(2)15例患儿共检测出7种突变,包括IVS2-13A/C>G、I172N、R356W、E3Δ8bp、c.1064G>A、c.141C>A、c.121C>T。最常见的突变为IVS2-13A/C>G(40%),其余常见突变依次为R356W(17%)、I172N(17%)及E3Δ8bp(7%)。SW最常见的突变为IVS2-13A/C>G和R356W,其等位基因频率分别达50%和19%。SV患者最常见的突变为I172N,其等位基因频率为36%。(3)SW、SV中基因型与临床表型的阳性预测值分别为88%、100%。结论 IVS2-13A/C>G、R356W、I172N为21-羟化酶缺乏症患儿常见突变,山西省热点突变为IVS2-13A/C>G。经典型患儿基因型与临床表型具有明显相关性。     

ABCB1基因多态性与五酯胶囊对他克莫司增效作用的相关性研究

摘 要 目的：研究五酯胶囊对他克莫司增效作用与 ABCB1基因多态性的相关性研究。方法: 通过聚合酶链反应 限制性片段长度多态性(PCR RFLP)方法测定ABCB1 1236C>T(rs1128503)、ABCB1 2677G>T/A(rs2032582)和ABCB1 3435C>T(rs1045642)基因型,使用化学发光微粒子免疫分析技术(CMIA)检测他克莫司C0。采用协方差分析考察不同组别患者他克莫司C0/D的差异。结果: 无论是单独使用他克莫司,还是他克莫司与五酯胶囊合用,ABCB1 1236C>T、ABCB1 2677G>T/A、ABCB1 3435C>T 不同基因型及单倍型组的他克莫司C0/D均无显著差异（P>0.05）。结论: 五酯胶囊对他克莫司的增效作用与ABCB1 1236C>T、ABCB1 2677G>T/A、ABCB1 3435C>T基因多态性无关。     

服用他克莫司的肾移植患者ABCB1基因多态性与术后感染的相关性

目的:观察服用他克莫司(Tacrolimus)的肾移植受者ABCB1基因多态性对于术后感染发生的影响。方法:选取行肾移植手术并服用他克莫司的患者90例,根据术后是否存在感染分为感染组和对照组,检测所有患者的ABCB1基因型3435C>T,1236C>T和2677G>A/T。采用χ²检验,方差分析和独立样本T检验的方法对患者的基本临床资料进行检验。采用卡方检验比较感染组和未感染组的基因多态性频率分布差异。结果:患者C1236T,C3435T,G2677A/T等位基因频率,均符合Hardy-Weinberg平衡。感染组和非感染组患者的年龄,性别,体质量,临床诊断,吗替麦考酚酯(Mycophenolate Mofetil)的用量均没有显著性差异。2组患者的平均血药谷浓度在一年内均无统计学差异。C1236T单核苷酸多态性对肾移植术后感染发生的影响具有统计学意义(P=0.034)。G2677A/T突变的发生对肾移植术后感染发生的影响具有统计学意义(P=0.010)。结论:ABCB1基因多态性中,仅C1236T的SNP多态性与G2677A/T的突变对肾移植术后感染发生的影响具有统计学意义。     

PS-1基因外显子5～9的突变研究

目的：筛查PS-1基因外显子5-9的突变，了解PS-1基因突变在中国人群中的分布情况及在中国人群阿尔茨海默病（AD）发病中可能产生的影响。方法：利用PCR-SSCP分析技术对120例正常体检人群PS-1基因外显子5-9进行突变筛查。结果：在这5个外显子中未发现任何突变，但在内含子9中第16位核苷酸处发现一种基因多态性位点，T／G基因型频率为65．8％，T／T基因型的频率为34．2％，未发现GiG基因型；等位基因T的频率为67．1％，等位基因G的频率为32．9％。结论：PS-1基因外显子5-9的突变频率较低，可能不是中国人群AD的主要危险因素：内含子9多态性与AD之间的关系还需进一步研究证实。     

VKORC1基因多态性对汉族静脉血栓栓塞患者服用华法林剂量的影响

目的探讨VKORC11173C>T和3730G>A基因多态性与静脉血栓栓塞患者服用华法林剂量的关系。方法应用扩增受阻突变体系聚合酶链式反应技术(ARMS-PCR)对205例华法林治疗达标患者(INR2-3)的VKORC1的1173C>T和3730G>A位点进行基因分型。结果205例患者中,在VKORC11173位点,CC型患者2例(1.0%),CT型25例(12.2%),TT型178例(86.8%);C等位基因频率7.1%,T等位基因频率92.9%。在VKORC13730位点,AA型2例(1.0%),GA型26例(12.7%),GG型177例(86.3%);G和A的基因频率分别为7.3%和92.7%。VKORC11173位点和3730位点存在着强烈连锁不平衡关系(D’=0.77,r2=0.58)。VKORC1的基因型差异与华法林维持剂量相关,VKORC11173的CC、CT和TT型患者的华法林维持剂量分别为(8.13±0.88)mg.d-1、(5.33±2.03)mg.d-1和(3.86±1.52)mg.d-1。VKORC13070的AA、GA和GG型患者的华法林维持剂量分别为(8.13±0.88)mg.d-1、(5.48±2.05)mg.d-1和(3.83±1.49)mg.d-1。单因素方差分析的结果显示,VKORC1两位点基因型对华法林维持剂量具有显著相关性(P均小于0.0001)。结论VKORC11173和3730位点对VTE患者服用华法林剂量有明显的影响。     

Single nucleotide polymorphisms of the pregnane x receptor gene in Han Chinese and a comparison with other ethnic populations

The pregnane X receptor (PXR/NR1I2) gene is a master regulator for a number of cytochrome P450s (CYPs) and drug transporters. This study aimed to detect the single nucleotide polymorphisms (SNPs) of the PXR gene in Han Chinese (n = 186) and to compare the frequencies of polymorphisms of the PXR gene with those in Caucasian and African Americans reported in the literature. The SNPs of the PXR gene were analyzed using the polymerase chain reaction (PCR) and direct sequencing analysis. The mutant frequencies of A11156C and T11193C in Han Chinese were 55% (95% confidence interval (CI): 0.49-0.61) and 59% (95% CI: 0.52-0.64), respectively, higher than those of Caucasian Americans (16 and 16%, respectively) and African Americans (33 and 30%, respectively). However, the reported SNPs in exons 2 and 4 (PXR*2,*3,*4,*6,*9,*10,and *11) were not detected in Han Chinese. These results indicate that there are marked differences in the mutant frequencies of A11156C and T11193C of PXR between Han Chinese and other ethnic groups. The mutant frequency in the coding region (exons 2 and 4) of PXR was very low in Han Chinese. Further studies are needed to determine the impact of common SNPs of PXR in Han Chinese and other ethnic populations on the phenotypic activity of cytochrome P450s and drug transporters transactivated by PXR.     

Distributive characteristics of Ser49Gly and Gly389Arg genetic polymorphisms of β1-adrenoceptor in Chinese Han and Dai populations

AIM: Genetic polymorphisms causing Ser49Gly and Gly389Arg mutants of beta(1)-adrenoceptor may result in significant changes in the function of this receptor. The aim of the present study was to investigate the frequencies of the Ser49Gly and Gly389Arg mutant alleles in healthy Chinese populations and to investigate the differences between 2 Chinese ethnic groups (Han and Dai populations) with respect to the frequencies of these alleles. METHODS: A total of 225 Han Chinese and 175 Dai Chinese unrelated healthy volunteers were recruited for this study. Genomic DNA was extracted from peripheral blood leukocytes by using a standard manual chloroform-phenol extraction. Fragments spanning the 2 polymorphisms were amplified by using polymerase chain reaction with template genomic DNA and relevant primers. The DNA products including the polymorphic loci were subjected to restriction endonuclease digestion with Eco0109I and BcgI. Digested fragments were detected with an ultraviolet detector after electrophoresis (100 V for approximately 1.5 h). RESULTS: The frequencies of the Gly49 and Arg389 alleles were, respectively, 16.2% and 76.4% in the Han population and 14.6% and 75.7% in the Dai population. CONCLUSION: The polymorphisms causing the Ser49Gly and Gly389Arg mutations of the beta(1)-adrenoceptor existed in both healthy Han and Dai Chinese populations. The frequencies of the Ser49Gly and Gly389Arg mutant alleles were not significantly different in the Han and Dai populations. However, the frequency of the Gly389 variant seems to be significantly lower in these 2 populations than in an African-American population.     

中国健康汉族和维吾尔族人谷胱甘肽硫转移酶的基因多态性

目的 比较中国健康汉族人和维吾尔族人GSTM1、GSTT1和GSTP1基因多态性分布。方法 用多重PCR分析GSTM1和GSTT1基因多态性，PCR—RFLP检测GSTP15号外显子105位密码子基因多态性。结果 汉族人与维吾尔族人的GSTM1纯合缺失频率接近。分别为56.1％和53.2％。而汉族人的GSTT1纯合缺失频率（50．0％）较维吾尔族人（26．6％）高。汉族人GSTP1 105I／I、I／V和V／V基因型频率分别为60．7％，35．2％和4．1％；维吾尔族人分别为51．3％，40．2％and 8．4％。结论 维吾尔族人与汉族人，除GSTM1外，GSTT1与GSTP1突变基因型频率存在明显种族差异。     

A comparison of glutathione S-transferase mutant frequencies in healthy Han and Uygur Chinese.

OBJECTIVE: This study was to compare the frequencies of genetic polymorphisms of GSTM1, GSTT1, and GSTP1 in Uygur Chinese with those in Han Chinese. METHODS: GSTM1 and GSTT1 polymorphisms were analyzed by a PCR-Multiplex procedure, whereas GSTP1 polymorphism was analyzed by PCR-RFLP. RESULTS: The frequency of GSTM1 null genotype in Han Chinese (56.1%) was similar to that in Uygur Chinese (53.2%) (P = 0.592), whilst the frequency of GSTT1 null genotype in Han Chinese (50.0%) was significantly (P < 0.05) higher than that of Uygur Chinese (26.6%). GSTP1 had a genotype distribution of 60.7% I/I, 35.2% I/V and 4.1% V/V in Han Chinese, and 51.3% I/I, 40.2% I/V and 8.4% V/V in Uygur Chinese. CONCLUSION: There is marked ethnic difference in the mutant frequencies of GSTT1 and GSTP1, but not GSTM1, between Uygur and Han Chinese.     

Eleven novel single nucleotide polymorphisms in the NR1I2 (PXR) gene, four of which induce non-synonymous amino acid alterations

Eleven novel single nucleotide polymorphisms (SNPs) were found in the NR1I2 (PXR/SXR) gene from 205 Japanese subjects. The detected SNPs were as follows: 1) SNP, MPJ6_1I2001; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-TTTCTACCTCTAC/TTATTGAAAGGGC-3'. 2) SNP, MPJ6_1I2004; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-AGGCCCAAATGTG/AAGTGATGCATAG-3'. 3) SNP, MPJ6_1I2007; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-TGCCAGGCCTGCC/TGCCTGCGCAAGT-3'. 4) SNP, MPJ6_1I2008; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-GAGTGAGCAGTGG/CGCGCGCGGGCGG-3'. 5) SNP, MPJ6_1I2010; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-CAGAGGAGCAGCG/AGATGATGATCAG-3'. 6) SNP, MPJ6_1I2011; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-CTGGAAGTGGCCA/GGGAGGTTCAAAG-3'. 7) SNP, MPJ6_1I2013; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-TCTTCCTCTCGCC/TCCCAACTTCTGG-3'. 8) SNP, MPJ6_1I2017; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-ATTGAATGCAATC/TGGCCCCAGCCTG-3'. 9) SNP, MPJ6_1I2018; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-GGTGAGCACAGCA/GGGGGGTGAGGAC-3'. 10) SNP, MPJ6_1I2019; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-GAGCTCCGCAGCA/GTCAATGCTCAGC-3'. 11) SNP, MPJ6_1I2021; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-GGTGACACCTCCG/AAGAGGCAGCCAG-3'. The frequencies were 0.0293 for MPJ6_1I2021, 0.0073 for MPJ6_1I2011, and 0.0024 for the other 9 SNPs. All SNPs were found as heterozygous. Among these SNPs, MPJ6_1I2007, MPJ6_1I2010, MPJ6_1I2017 and MPJ6_1I2019 induce non-synonymous amino acid alterations (R98C, R148Q, R381W and I403V, respectively, in PAR1).     

用基因芯片技术测定健康人群P450 2C9基因多态性

目的 探讨基因芯片技术在P450 2C9基因分型中应用的可行性，研究中国人群P450 2C9基因多态性。方法 用基因芯片技术测定169例中国健康志愿者P4502C9基因分型，并用直接测序法对结果进行验证。结果 169例中国健康志愿者中，共发现9名P450 2C9*1／*3基因型，P450 2C9*3／*3基因型1名，无P4502C9*2，P450 2C9*4和P450 2C9*5变异。结论 基因芯片法适用于中国健康人群P450 2C9基因分型研究，健康人群：P450 2C9％3等位基因频率为0．03。