PRKAA1和UNC5CL基因位点多态性与胃癌的相关性研究

目的:研究PRKAA1和UNC5CL基因位点多态性与胃癌发病的关系。方法:以我院2014年1月~2016年12月收治的90例胃癌患者为观察组,选择同期在我院进行治疗的90例胃炎患者作为对照组。提取分析患者的全血DNA样品,对其PRKAA1和UNC5CL基因位点基因分型进行检测,并进行组间比较。结果:(1)与对照组比较,观察组PRKAA1基因的rs13361707位点的CC型基因出现频率、rs10074991位点的GG基因出现频率、rs10036575位点的TT基因出现频率均显著高于对照组,rs10036575位点的CT+CC基因出现频率显著低于对照组,差异均具有统计学意义(P0.05)。(2)观察组UNC5CL基因的rs2294693、rs742494位点的各基因分型的出现频率与对照组间比较差异无统计学意义(P0.05)。结论:胃癌患者的发病与PRKAA1基因多态性表达有一定的相关性,当rs13361707位点为CC型、rs10074991位点为GG型、rs10036575位点为TT型时,胃癌的发病率增加,当rs10036575位点为CT+CC型时,胃癌发病率降低。而胃癌患者的发病与UNC5CL基因位点多态性表达无明显相关性。     

干扰素诱导跨膜蛋白3rs12252单核苷酸多态性与乙型流感临床严重程度的相关性研究

为了研究干扰素诱导的跨膜蛋白3(Interferon-induced transmembrane protein 3,IFITM 3)rs12252单核苷酸多态性(Single nucleotide polymorphism,SNP)与乙型流感临床严重程度的相关性,在吉林省和湖南省收集了181名乙型流感轻症病例和83名乙型流感重症病例全血标本,提取两组病例基因组DNA并扩增相应的目的片段后,采用Sanger测序的方法对ITIM3rs12252SNP进行基因分型。同时选用千人基因组103名中国北京地区汉族人(CHB)为一般人群对照。统计分析结果表明,轻症病例IFITM 3rs12252基因型频率分布与一般人群对照无显著性差异,但重症病例rs12252CC基因型频率显著高于一般人群对照组。乙型流感重症病例IFITM3rs12252C等位基因频率显著高于轻症病例(P0.05),携带rs12252-C等位基因发展为乙型流感重症的风险是rs12252-T等位基因的1.818倍(Odds Ratio=1.818,95%CI:1.241~2.664)。并且重症病例中rs12252CC基因型频率显著高于轻症病例(P0.05),表明rs12252CC基因型与乙型流感重症相关。     

癫痫患儿SCN1A、MDR1 G2677TA、ABCB1 C3435T基因多态性与左乙拉西坦治疗效果的关系及疗效的影响因素分析

摘要 目的：探讨癫痫患儿SCN1A、MDR1 G2677TA、ABCB1 C3435T基因多态性与左乙拉西坦（LEV）治疗效果的关系及疗效的影响因素。方法：选择2019年6月至2021年7月在本院接受LEV治疗的癫痫患儿226例为研究对象,分析所有患儿基因型和等位基因分布情况;治疗3个月后根据治疗效果分为有效组和无效组,分析两组患儿SCN1A、MDR1 G2677TA、ABCB1 C3435T基因型及等位基因频率分布;采用单因素及多因素Logistic回归分析法分析影响临床疗效的因素。结果：癫痫患儿SCN1A rs4667869、SCN1A rs10497275、MDR1 G2677TA、ABCB1 C3435T基因型及等位基因分布频率有统计学差异（P＜0.05）。有效组SCN1A rs4667869的基因型GG、GC及等位基因G分布频率高于无效组（P＜0.05）,基因型CC及等位基因C分布频率低于无效组（P＜0.05）;有效组SCN1A rs10497275的基因型GA及等位基因G高于无效组（P＜0.05）,基因型AA及等位基因A分布频率低于无效组（P＜0.05）;有效组MDR1 G2677TA的基因型GT、TT及等位基因T高于无效组（P＜0.05）,基因型GG、AA及等位基因G分布频率低于无效组（P＜0.05）;有效组ABCB1 C3435T的基因型CC、CT及等位基因C分布频率高于无效组（P＜0.05）,基因型TT及等位基因T分布频率低于无效组（P＜0.05）。单因素分析显示,月发作频率和出生窒息史与LEV治疗癫痫患儿疗效有关。多因素Logistic回归分析显示,SCN1A rs4667869、SCN1A rs10497275、MDR1 G2677TA和ABCB1 C3435T基因型及等位基因、出生窒息史是LEV治疗癫痫患儿疗效的影响因素。结论：癫痫患儿SCN1A、MDR1 G2677TA和ABCB1 C3435T基因多态性与LEV治疗效果有关,其多种基因型是LEV治疗效果的影响因素。     

SLC6A4基因多态性与海洛因依赖的关联性研究

目的:探讨5-羟色胺转运体基因(solute carrier family 6 member 4,SLC6A4)基因4个单核苷酸多态性(single nucleotide polymorphism,SNP)位点与海洛因依赖之间的关系。方法:严格按照诊断标准,选取无亲缘关系的海洛因依赖个体397例(病例组)及健康对照个体402例(对照组)提取基因组DNA,采用SNaPshot SNP分型技术对SLC6A4基因4个SNP位点(rs1042173,rs3813034,rs6354,rs7224199)进行基因分型,比较病例-对照组间各位点等位基因、基因型频率的差异。结果:病例组和对照组SLC6A4基因rs1042173和rs3813034位点的基因型和等位基因频率比较存在显著性差异(P0.05),rs1042173的C等位基因(P=0.031,OR=1.317,95%CI=1.026-1.691)及rs3813034的C等位基因(P=0.013,OR=1.375,95%CI=1.069-1.768)是海洛因依赖的危险因素。病例组TCC单倍型(rs7224199、rs3813034和rs1042173)的比例较对照组显著增高(P0.05)。结论:SLC6A4基因rs1042173和rs3813034多态性可能与海洛因成瘾有关,携带有rs1042173的C等位基因和rs3813034的C等位基因的个体及携带TCC单倍型的个体可能更容易对海洛因产生依赖。     

北部湾人群Dectin-1的基因多态性与马尔尼菲青霉菌病易感性的相关性研究

目的:探讨北部湾人群C型凝集素-1(Dectin-1)基因多态性与马尔尼菲青霉菌病易感性的相关性。方法:选取北部湾地区的马尔尼菲青霉菌(PM)病患者71例为病例组,另选北部湾地区的71例体检正常者为对照组,直接测序检测rs16910526、rs16910527位点的基因型及等位基因频率,并分析其与马尔尼菲青霉菌病易感性的相关性。结果:(1)对照组和病例组之间rs16910526有三种基因型GG、GT、TT,两组之间基因型和等位基因频率比较差异不显著(P0.05)。(2)对照组和病例组之间rs16910527有三种基因型AA、AC、CC,且病例组AC的基因型频率显著高于对照组(P0.05)。(3)局限性、播散性PM患者rs16910526、rs16910527基因型和等位基因频率比较差异不显著(P0.05)。(4)rs16910526、rs16910527的4种单倍型:GT、AC、AT、TT,位于同一连锁不平衡区域内,且对照组和病例组A/C的分布频率比较差异具有统计学意义(P0.05)。结论:北部湾人群Dectin-1的rs16910527位点与马尔尼菲青霉菌病易感性相关,且A/C能提高马尔尼菲青霉菌病的易感性。     

急性髓系白血病ERG、MDR1及BAALC基因的表达水平及临床意义

目的:探讨急性髓系白血病(acutemyeloidleukemia,AML)患者骨髓单个核细胞的ETS相关基因(ETS related gene,ERG)、多药耐药基因1(Multidrug resistance gene 1,MDR1)、脑和急性白血病胞质(Brain and acute leukemia cytoplasmic,BAALC)基因的表达水平及临床意义。方法:选取90例成人AML患者为研究对象,均接受蒽环类药物诱导化疗联合阿糖胞苷等进行初步治疗,采用实时荧光定量检测PCR技术检测治疗后的骨髓单个核细胞ERG、MDR1、BAALC基因表达,并分析其与患者临床特征、危险度分层、治疗疗效、生存率的关系。结果:AML患者ERG、MDR1、BAALC基因均有强表达,三因子表达强弱同白细胞、血小板等临床指标无明显相关性(P0.05),不同危险度分层对应的ERG、MDR1、BAALC表达之间有明显差异,中危组、高危组患者表达强度均高于低危组(P0.05)。ERG、MDR1低表达组对应的疗效CR(93.1%%,89.6%)、OS(56.5%, 66.7%)较高表达组CR(61.4%, 81.3%)、OS(56.5%,66.7%)值更高(P0.05),不同BAALC表达者疗效CR及生存率OS比较差异无统计学意义(P0.05)。结论:AML患者单个核细胞的ERG、MDR1基因表达水平与其危险度分层、疗效和生存率呈负相关,以REG和MDR1同AML关系敏感,BAALC敏感度较低,联合检测REG、MDR1、BAALC基因表达可能提高AML患者危险度分层、疗效及预后判读的准确度。     

apelin基因rs2235306位点多态性与哮喘的相关性研究

目的:探讨apelin基因rs2235306位点多态性与哮喘的相关性。方法:以外周血全血DNA为模板,应用四引物扩增受阻突变体系PCR(Tetra-primer ARMS PCR,T-ARMS-PCR)方法对158例哮喘患者(AS)和79例健康个体(NC)apelin基因rs2235306位点基因型进行分析,同时进行肺功能检查(FEV1、FVC、FEV1/FVC)。结果:AS组和NC组apelin基因rs2235306位点等位基因T和C频率分布具有统计学意义(X2=6.906,P=0.009,OR=1.688,95%CI=1.140-2.497),AS组C等位基因频率显著高于健康对照组;AS组和NC组基因型分布具有统计学意义(X2=14.243,P=0.000,OR=3.894,95%CI=1.861-8.149),其中CC基因型患哮喘的风险较高,为TT+TC基因型的3.894倍。AS轻度组和AS中重度组基因型CC和TT+TC频率及等位基因T和C频率比较均无统计学意义。结论:apelin基因rs2235306位点多态性和哮喘的发病具有一定的相关性,C等位基因可能是哮喘的遗传易感基因,CC基因型携带者哮喘的患病风险可能增加,但与哮喘的严重程度无明显相关性。     

P21WAF1基因单核苷酸多态性和东北地区HPV相关宫颈癌的关系

研究P21WAF1基因单核苷酸多态性与中国东北地区人群HPV阳性宫颈癌风险的关系.以聚合酶链反应-直接测序的方法分析了340例宫颈癌患者标本P21WAF1基因rs1801270和rs3176352多态性,比较不同基因型与宫颈癌风险的关系.rs3176352多态在宫颈癌患者中的分布和正常对照组差异不显著,与宫颈癌风险无关.rs1801270多态在宫颈癌患者中的分布和正常对照组差异显著,宫颈癌患者中C等位基因频率、CC和AC基因型频率明显高于正常对照组(P＜0.05);与携带A等位基因者比较,携带C等位基因者罹患宫颈癌的风险增加1.366 7倍(95％ CI:1.1121～1.6792).P21WAF1基因rs1801270多态C等位基因是东北地区人群宫颈癌遗传易感因素.     

KDR rs1870377基因与经皮冠状动脉介入治疗术后氯吡格雷耐药相关性分析

摘要 目的：探讨与分析KDR rs1870377基因与经皮冠状动脉介入治疗（percutaneous coronary intervention, PCI）术后氯吡格雷耐药相关性。方法：2018年5月到2021年2月选在航天中心医院（北京大学航天临床医学院）老年医学一科住院的冠心病患者97例作为研究对象,所有患者在PCI术后判定氯吡格雷耐药情况,检测KDR rs1870377基因多态性状况并进行相关性分析。结果：在97例患者中,PCI术后氯吡格雷耐药22例(耐药组),耐药率为22.7 %。耐药组的空腹血糖、总胆固醇、甘油三酯等与非耐药组对比差异无统计学意义（P>0.05）。KDR rs1870377基因主要包括AA、CC、CA三种基因型,两组都与Hardy-Weinberg平衡定律相符合,研究对象具有群体代表性。耐药组的KDR rs1870377基因CC基因型高于非耐药组（P<0.05）,耐药组的等位基因C频率高于非耐药组（P<0.05）。Spearsman分析显示KDR rs1870377基因CC基因型、等位基因C与氯吡格雷耐药存在相关性（P<0.05）。多元Logistic回归分析显示KDR rs1870377基因CC基因型、等位基因C为导致PCI术后氯吡格雷耐药的重要因素（P<0.05）。结论：冠心病患者PCI术后氯吡格雷比较常见,也伴随有KDR rs1870377基因多态性,KDR rs1870377基因CC基因型、等位基因C为导致PCI术后氯吡格雷耐药的重要因素。     

广西壮族人群EBI3 基因rs6613A/T, rs4905A/G多态性分布特点

目的:分析广西壮族人群EBI3基因rs6613A/T、rs4905A/G多态性分布特点。方法:采用单碱基延伸的PCR技术对168例广西壮族人群EBI3 rs6613 A/T和EBI3 rs4905A/G进行多态性检测,对比国际人类基因组计划(Hap Map)公布的中国北京人、日本人、非洲人和意大利人的SNP分型数据,分析5个人群rs6613 A/T、rs4905A/G位点的基因型和等位基因频率差异。结果:在广西壮族人群中,EBI3基因rs6613 A/T位点AT基因型最常见,约为49.4%;T等位基因频率最高,约为52.1%;rs4905A/G多态性位点AC基因型最常见,约为48.2%;C等位基因频率最高,约为50.9%。EBI3基因型及等位基因频率分布于性别无显著相关性(P0.05)。广西壮族人群EBI3基因rs6613A/T位点基因型和等位基因频率与北京人差异无统计学意义(P0.05),但与非洲人、日本人、意大利人差异具有统计学意义(P0.05);EB-13基因rs4905A/G位点基因型和等位基因频率与北京人和日本人差异无统计学意义(P0.05),但与非洲人和意大利人比较差异具有统计学意义(P0.01)。结论:EBI3基因rs6613 A/T和EB-13 rs4905A/G多态性位点基因型和等位基因在广西壮族人群中的分布频率与其他种族和地区人群相比存在差异,这种差异可能是导致某些疾病在不同人群发病率和临床表现存在差异的原因之一。     

血清白介素8基因多态性与食管鳞癌根治术后的相关性分析

摘要 目的：探讨与分析血清白细胞介素8（IL-8）基因多态性与食管鳞癌（ESCC）根治术后的相关性。方法：2017年8月到2020年6月选择在本院诊治的食管鳞癌患者98例作为研究对象,检测血清IL-8表达水平。所有患者都给予根治手术治疗,随访患者的预后并进行相关性分析。结果：所有患者术后随访到2021年7月,平均随访时间为25.69±2.58个月,死亡28例,死亡率为28.6 %（死亡组）。两组血清IL-8表达水平表达具有差异（P<0.05）。所有患者的基因型频率均符合Hardy-Weinberg这一平衡法则,表明本文所选取的样本均具有群体代表性。IL-8基因启动子rs4073A/T的AA基因型较死亡组高,TT基因型较死亡组低,两组A、T等位基因频率分布对比有差异（P<0.05）。直线相关性分析显示：IL-8基因启动子rs4073A/T的AA基因型、A等位基因、血清IL-8表达水平与预后死亡率存在相关性（P<0.05）。多因素logistic回归分析显示：IL-8基因启动子rs4073A/T的AA基因型、A等位基因、血清IL-8表达水平为导致患者随访死亡的主要因素（OR=2.051,3.094,P<0.05）。结论：食管鳞癌根治术后患者依然存在一定的死亡率,患者死亡与血清IL-8基因多态性存在相关性,同时多伴随有IL-8的高表达。IL-8基因启动子rs4073A/T的AA基因型、A等位基因、血清IL-8表达水平为导致患者死亡的主要因素。     

新疆地区维吾尔族和汉族人群CaSR基因多态性与草酸钙肾结石关系的研究

目的:探讨新疆地区维吾尔族和汉族草酸钙结石与钙敏感受体(calcium sensitive receptor,Ca SR)基因多态性之间的关系。方法:选择398例临床确诊泌尿系草酸钙结石患者(200例维吾尔族,198例汉族)和399例正常对照者(200例维吾尔族,199例汉族),应用Sna Pshot方法对Ca SR基因两位点(rs1042636,rs1801726)的基因型及等位基因频率进行检测,并分析其与草酸钙结石发病的相关性以及对血钙、24 h尿钙水平的影响。结果:各组2个位点的基因型分布均符合Hardy-Weinberg平衡。汉族结石组与汉族对照组及维吾尔族结石族与维吾尔族对照组rs1042636、rs1801726位点基因型分布及基因频率差异均无统计学意义(P0.05)。维吾尔和汉族rs1042636基因型及等位基因频率比较差异有统计学意义(P0.05),且维吾尔族人群携带rs1042636等位基因A的风险高于汉族人群(病例组中OR值=2.145,%95CI=[1.602~2.866],P0.01;对照组中OR值=1.773,%95CI=[1.332~2.359],P0.01),其中维/汉病例组中等位基因频率分别为A=278(69.5%)/204(51.5%),G=122(30.5%)/192(48.5%);维/汉对照组中等位基因频率分别为A=264(66.0%)/208(52.3%),G=136(34.0%)/190(47.7%)。而病例组和对照组rs1801726基因型频率差异无统计学意义(P0.05);汉族病例组、对照组发现GG+AG基因型较AA基因型有较高的尿钙水平(病例组:P=0.007和对照组:P=0.006),维吾尔族人群该位点与两项指标无相关性。结论:Ca SR基因2个基因位点rs1042636、rs1801726可能不是新疆地区维吾尔族和汉族草酸钙结石发病的危险因子,两族rs1042636基因多态性分布存在差异,rs1042636位点基因多态性能影响汉族人群尿钙排泄,可能汉族调节钙排泄的遗传因素之一。     

Association Study between Polycystic Ovarian Syndrome and the Susceptibility Genes Polymorphisms in Hui Chinese Women

IntroductionPolycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders. Evidence of familial aggregation analysis and different clinical traits among different regions and ethnicities indicated that the pathogenesis of PCOS is associated with multiple genetic and environmental factors. Our previous research had identified three susceptibility loci (rs2479106, DENND1A; rs13405728, LHCGR; rs13429458, THADA) for PCOS in Han Chinese women. The overall aim of this study was to investigate the relationship between three susceptibility gene polymorphisms and PCOS in Hui ethnic women.Methods151 patients with PCOS (case group) and 99 healthy women (control group) were recruited from the Reproductive Medicine Center of the General Hospital of Ningxia Medical University. Clinical data and serum hormone characteristics of case and control groups were collected and analyzed. The three susceptibility single-nucleotide polymorphisms have been replicated in both case and control groups. Gene polymorphisms were detected by direct sequencing after polymerase chain reaction.ResultsThe Body Mass Index, LH, LH/FSH ratio and total testosterone were significantly elevated in PCOS patients compared to control group (P<0.05). The frequencies of genotype and allele in rs13405728 were significantly different between the PCOS and the control groups (P<0.05). Of the SNP rs13405728, the PCOS cases with TT genotype stayed at a higher level of total testosterone, TG and LDL than those with the CC and CT genotypes. In contrary, there was no statistical difference between the two groups for SNP rs13429458 and rs2479106 (P>0.05).ConclusionThe present study suggested that the SNP rs13405728 in the LHCGR gene was associated with PCOS in Hui ethnic women, and its TT genotype characterized with higher level of TT, TG and LDL.     

The Polymorphisms in LNK Gene Correlated to the Clinical Type of Myeloproliferative Neoplasms

ObjectiveLNK is an adapter protein negatively regulating the JAK/STAT cell signaling pathway. In this study, we observed the correlation between variation in LNK gene and the clinical type of myeloproliferative neoplasms (MPN).MethodsA total of 285 MPN cases were recruited, including essential thrombocythemia (ET) 154 cases, polycythemia vera (PV) 76 cases, primary myelofibrosis (PMF) 19 cases, and chronic myeloid leukemia (CML) 36 cases. Ninety-three healthy individuals were used as normal controls. V617F mutation in JAK2 was identified by allele-specific PCR method, RT-PCR was used for the detection of BCR/ABL1 fusion gene, and mutations and variations in coding exons and their flanking sequences of LNK gene were examined by PCR-sequencing.ResultsMissense mutations of A300V, V402M, and R415H in LNK were found in 8 patients including ET (4 cases, all combined with JAK2-V617F mutation), PV (2 cases, one combined with JAK2-V617F mutation), PMF (one case, combined with JAK2-V617F mutation) and CML (one case, combined with BCR/ABL1 fusion gene). The genotype and allele frequencies of the three SNPs (rs3184504, rs111340708 and rs78894077) in LNK were significantly different between MPN patients and controls. For rs3184504 (T/C, in exon2), the T allele (p.262W) and TT genotype were frequently seen in ET, PV and PMF (P<0.01), and C allele (p.262R) and CC genotype were frequently seen in CML (P<0.01). For rs78894077 (T/C, in exon1), the T allele (p.242S) was frequently found in ET (P<0.05). For rs111340708 (TGGGGx5/TGGGGx4, in intron 5), the TGGGG x4 allele was infrequently found in ET, PMF and CML(P<0.01).ConclusionMutations in LNK could be found in some of MPN patients in the presence or absence of JAK2-V617F mutation. Several polymorphisms in LNK gene may affect the clinical type or the genetic predisposition of MPN.     

LKB1基因多态性与2型糖尿病相关性研究

目的:探讨陕西汉族人群中LKB1基因位点rs741765(380CT)及rs6510599(459GA)单核苷酸多态性(SNPs)与2型糖尿病遗传易感性及相关临床代谢指标的关系。方法:采用等位基因特异性引物PCR(SASP-PCR)对2型糖尿病患者130例及健康对照组100例进行LKB1基因内含子6 rs741765(380CT)及内含子1 rs6510599(459GA)两个位点进行基因多态性筛查,并测序鉴定,分析其基因多态性位点与2型糖尿病临床代谢指标关系。结果:rs741765(380CT)基因突变情况:2型糖尿病患者TT基因型频率显著高于健康对照组(P=0.023);TT基因2型糖尿病组中糖化血红蛋白水平及低密度脂蛋白胆固醇水平在型中明显升高(P=0.030;P=0.002);健康对照组中,空腹血糖水平在TT基因型中明显升高(P=0.011)。rs6510599(459GA)基因突变情况:AA基因型频率在2型糖尿病组及健康对照组间无显著性差异(P0.05);该基因位点与临床指标亦无相关性(P0.05)。结论:陕西汉族人群中LKB1基因内含子6 rs741765(380CT)及内含子1 rs6510599(459GA)存在基因多态性。LKB1基因内含子6 rs741765(380CT)基因多态性与2型糖尿病的发病有相关性。LKB1基因内含子1 rs6510599(459GA)基因多态性与2型糖尿病的发病无相关性。     

Effect of metabolic syndrome risk factors and MMP-2 genetic variations on circulating MMP-2 levels in childhood obesity

Matrix metalloproteinase-2 is involved in the development of the adipose tissue, and associated with cardiovascular diseases. Metabolic risk factors (MRFs) and functional polymorphisms in the MMP-2 gene may affect its expression and activity. We investigated whether traditional MRFs and two MMP-2 gene polymorphisms (C^?1306T; rs243865, and C^?735T; rs2285053) affect circulating MMP-2 levels in children and adolescents, and whether MMP-2 polymorphisms and/or haplotype are associated with susceptibility to childhood obesity. We studied 114 healthy controls, 43 obese, and 83 obese with ≥3 MRFs children and adolescents. Genotypes were determined by Taqman allele discrimination assay and real-time PCR. Plasma MMP-2 was measured using zymography. We found positive correlations between MMP-2 concentrations and mean blood pressure in all children and adolescents group (r = 0.132; P < 0.05) and in obese children and adolescents (r = 0.247; P < 0.01). We found that the CC genotype for the C^?1306T polymorphism was more common in subjects with higher MMP-2 concentrations in controls (P = 0.003) and in the obese group (P = 0.013). The CT genotype (OR = 0.40; P < 0.01) and the T allele (OR = 0.48; P < 0.01) for the C^?735T polymorphism were less common in obese children and adolescents than in controls. The haplotypes distribution did not show significant differences between control and obese (P > 0.05). Ours findings show that blood pressure is associated with circulating MMP-2 concentrations, and that the CC genotype for the C^?1306T polymorphism was more common subjects (controls and obese) with higher MMP-2 concentrations, whereas the CT genotype and the T allele for the C^?735T polymorphism are less common in obesity.