COMT基因Val158Met多态性在BRCA1/2基因无突变的遗传倾向乳腺癌中的分布

目的探讨Catechol-O-methyhransferase（COMT）基因Val158Met（G→A）多态性在BRCA1／BRCA2基因无突变的具有遗传倾向乳腺癌人群中的分布及其与乳腺癌发病风险的相关性。方法对114例无BRCA1／BRCA2突变的家族性或早发性乳腺癌患者和121例正常对照者进行COMT基因第4外显子的聚合酶链反应扩增,随后进行DNA直接测序鉴定Val158Met多态的基因型,比较基因型分布和发病风险的关系;相对危险比值比（oddratio,OR）及95％可信区间（confidence interval,CI）应用非条件Logistic回归分析计算。结果COMT基因Val158Met多态的GG,GA和AA基因型在病例组中的分布频率分别为0．58（65例）,0．32（36例）和0．10（11例）;在对照组的分布频率分别为0．60（66例）,0．37（41例）和0．03（3例）。在早发性乳腺癌人群中,含A基因型的频率为0．57（21例）,显著高于家族性乳腺癌的0．35（26例）（P=0．026）。以GG基因型为参照,AA基因型（158Met）显著提高了乳腺癌的发病危险（OR=3．15;95％CI：0．70～14．19）（P=0．039）,在绝经前妇女尤为明显（OR=9．98;95％CI：1．00～99．64）（P=0．004）;在体质指数（body mass index,BMI）≤23kg／m^2的妇女中,AA纯合基因型（158Met）临界显著提高了乳腺癌的发病危险（OR=7．57;95％CI：0．57～101．28）（P=0．056）。结论COMT基因Val158Met可能与乳腺癌、特别是绝经前或早发性乳腺癌的遗传易感性有关,可作为低外显率的乳腺癌易感基因位点。     

多囊卵巢综合征患者胰岛素受体基因外显子17多态性的研究

目的探讨胰岛素受体（INSR）基因外显子17多态性与多囊卵巢综合征（PCOS）发病的关系。方法应用聚合酶链反应限制性内切酶片段长度多态性分析（PCR—RFLP）法对中国汉族96例PCOS患者和56例对照者INRS基因外显子17第1,058位点的多态性进行检测,分析并比较INRS基因外显子17第1,058位点T、C等位基因频率与PCOS胰岛素抵抗、高雄激素血症之间的关系。结果（1）PCOS患者INSR基因外显子17第1,058位点T等位基因出现频率为41．7％,明显高于正常对照组的14．3％（P〈0.05）。（2）PCOS患者出现T等位基因者的体重指数（BMI）明显低于出现C等位基因患者（P〈0.05）。（3）PCOS胰岛素抵抗组与非胰岛素抵抗组T、C等位基因出现频率无统计学差异（P〉0．05）。（4）PCOS高雄激素组与无高雄激素组INSR基因T、C等位基因频率无统计学差异（P〉0．05）。结论INSR基因17外显子C／T单核酸多态性与PCOS患者肥胖密切相关,与PCOS的高雄激素血症、胰岛素抵抗（IR）无明显关系。认为INSR基因第17外显子C／T单核酸多态性仅系PCOS的一个易感基因,对PCOS的发病无决定性作用。     

中国汉族NOS2基因多态性与白癜风发病相关性研究

目的：探讨NOS2基因-954G→C位点多态性与白癜风发病的相关性。方法：采用聚合酶链反应和限制性片段长度多态性方法，对749例白癜风患者和763例健康人的NOS2基因-954G→C位点基因型进行分析。结果：白癜风患者NOS2-954G→C位点基因型的分布与正常对照组相比有显著性差异，联合基因型GC＋CC及C等位基因在白癜风患者中频率较高，与临床资料结合分析表明联合基因型GC＋CC在在发病年龄大于20岁组、活动期患者、皮节型白癜风及伴有自身免疫病和正常对照组之间无显著差异（P〉0．05），但在发病年龄小于20岁组、稳定期患者、寻常型白癜风及无自身免疫病组的分布频率与正常对照组相比有显著性差异（P〈0．05）。结论：NOS2-954G→C位点基因多态性与白癜风有明显的相关性。携带C等位基因可能会增加对白癜风的易感性。     

MYH9基因多态性与汉族 IgA 肾病病理关系的研究

目的：探讨 MYH9基因多态性与汉族 IgA 肾病病理的关系。方法：经肾组织活检确诊的 IgA 肾病患者148例作为研究对象,取外周血提取 DNA,采用限制性片段长度多态性分析（PCR - RFLP）法检测 MYH9基因 Rs3752462基因多态性,研究其与 IgA 肾病病理的相关性。结果：（1）Rs3752462位点群体符合哈温平衡;（2）Rs3752462位点基因型与病理 HASS分级差异无统计学意义。结论：MYH9基因 Rs3752462位点基因多态性与 IgA 肾病病理无明显相关性。     

先天性巨结肠症内皮素受体B基因的多态性研究

目的观察中国汉族散发性先天性巨结肠症（sHD）G蛋白藕联受体家族的内皮素受体-B（EDNRB）易感基因的突变与多态性特征，探讨碱基改变与先天性巨结肠症的发病关系。方法收集104例散发性先天性巨结肠与其中42例患儿（子代组）的双亲血样，120例正常儿童作对照，聚合酶链反应-单链构象多态性（PCR—SSCP）与DNA测序确定并比较EDNRB基因外显子1、2的突变与多态性位点（SNPs）等位基因与基因型分布差异，分析sHD表型与SNPs的关联，传递不平衡检验（TDT）分析三样本家系SNPs的传递不平衡。结果EDNRB基因外显子1、2均未发现突变，外显子1检测2个SNPs，c311A→T（N104I）为新发现位点；病例组c311A→T位点的等位基因和基因型频率均与对照组差异有统计学意义（P〈0．01），c99C→T位点的差异无统计学意义；TDT检验发现亲子代间在c311A→T（N104I）位点存在传递不平衡，杂合体双亲优先传递等位基因T给子代；临床表型与SNPs等位基因分布无明显关联。结论中国汉族散发性先天性巨结肠EDNRB基因的多态性可能在发病中起重要作用。     

基因测序筛选前列腺癌患者PCA3(DD3)基因外显子多态性

目的 筛查前列腺癌患者PCA3基因外显子单核苷酸多态性位点,初步探讨PCA3基因多态性与前列腺癌的相关性.方法 采用基因测序法对41例前列腺癌(PCa)患者和40例良性前列腺增生(BPH)患者进行PCA3基因外显子SNP位点的筛选,对筛选到的sNP位点进行前列腺癌的相关性分析.结果 PcA3基因外显子1、外显子3、外显子4区域均未检测到基因多态性位点,PCA3基因外显子2区域存在1个SNP位点(A→C),基因型分别为AA型、AC型、CC型,该位点的基冈型频率和等位基因频率与前列腺癌存在相关性(P<0.05).结论 基因测序可有效筛选到PCA3基因外显子的SNP位点,PCA3基因外显子2基因多态性可能与前列腺癌发病风险有关.     

检测血液p53基因SNP位点的多态性与病理性瘢痕基因型的相关性

目的探讨p53基因第72位密码子单核苷酸多态性，并分析该多态性位点与病理性瘢痕的相关性。方法常规抽取105例瘢痕患者和190例健康志愿者的血液，提取DNA，设计1对针对p53基因第4外显子第72密码子单核苷酸多态性荧光探针，进行实时定量PCR分析并观察图像。结果实时定量PCR技术检测能准确区分各种基因型，抽取295例血液样品中，基因型CCC有121例，基因型CGC有88例，基因型CCC／CGC有86例，通过PCR荧光分子信标检测p53基因第72密码子单核苷酸多态性的方法。CCC基因型患病理性瘢痕的概率最高，病理性瘢痕患者的年龄及发病部位与基因型有无相关性尚待进一步研究。结论CCC基因型及单核苷酸多态性可能与病理性瘢痕形成相关。     

胃癌与细胞毒性T淋巴细胞相关抗原-4基因启动子区域多态性的相关性研究

目的探讨细胞毒性T淋巴细胞相关抗原（CTLA）-4基因启动子区-1722位点（T／C）多态性和-1661位点（A／G）多态性与中国汉族人群中胃癌的相关性。方法采用聚合酶链反应（PCR）-限制性片段长度多态性（RFLP）方法，对183例胃癌患者和116例中国汉族正常对照者进行CTLA-4基因-1722位点和-1661位点多态性检测。结果与正常对照组比较，胃癌患者CTLA-4基因-1661位点AA基因型频率，-1661位点A等位基因频率显著降低（65．6％vs84．5％；P〈0．01；odds ratio=0．3499；95％CI=0．1943—0．6299；81．1％vs91．8％；P〈0．01；odds ratio=2．6040；95％CI=1．521—4．458）。结论CTLA-4基因启动子区-1661位点A等位基因与中国汉族胃癌显著相关。     

人脑胶质瘤抑癌基因p16的研究

目的 研究抑癌基因p16与原发胶质瘤发生、发展的内在关系。方法 使用PCR－温度梯度凝胶电泳（TGGE）的方法，对48例脑胶质瘤的第2外显子进行测定，研究p16的缺失和突变；同时选用甲基化敏感限制性内切酶与基因组DNA反应，然后进行PCR扩增了解p16的甲基化改变。结果 48例胶质瘤标本中，14例发生p16基因的纯合缺失，其中Ⅲ级为33％（5／15）；Ⅳ级为50％（9／18）。对34例p16扩增阳性标本进行TGGE检测，2例有点突变。48例标本中检测到第2外显子甲基化的有6例，2例为Ⅱ级胶质瘤，4例为Ⅲ级胶质瘤，甲基化率为12％（6／48）。结论 p16的改变可能与胶质瘤的发生有一定关系。其中以第2外显子的纯合缺失为主，第1外显子的甲基化为辅，而点突变很少发生。p16缺失主要发生在高级别的胶质瘤中，可能为肿瘤发生的较晚期事件。     

钙敏感受体基因第7外显子单核苷酸多态性与特发性高钙尿症的关系

目的了解钙敏感受体（CaSR）基因单核苷酸多态性与特发性高钙尿（IH）症的关系，探讨特发性高钙尿发病的分子机制。方法提取76例湖北地区汉族特发性高钙尿患者及126例健康对照者外周血标本中基因组DNA，应用聚合酶链反应（PER）结合DNA测序方法检测并分析了CaSR基因的第7外显子3个簇集的多态性位点单核苷酸多态性分布。结果特发性高钙尿病例和对照组CaSR基因的第7外显子第986、990多态性位点等位基因频率分布均符合Hardy-Wein-berg定律，其基因型分布频率在特发性高钙尿患者和正常对照者中差异无统计学意义（P〉0．05），第1011位未见有多态改变。但特发性高钙尿组组内CaSR 990位GG纯合子和RG杂合子个体的24h尿钙排泄量较RR纯合子明显增高，差异有统计学意义（P〈0．05）。结论CaSR基因不是特发性高钙尿的易感主基因，但第7外显子990位A／G单核苷酸多态性能影响尿钙排泄，可能是特发性高钙尿中调节钙排泄的遗传成分之一。     

福建地区汉族人群VDR基因TaqⅠ多态性与腰椎间盘退行性变的相关性研究

目的研究维生素D受体（VDR）基因TaqⅠ多态性与福建地区汉族人群腰椎间盘退行性变的关系。方法应用限制性片段长度多态性聚合酶链反应法（PCR-RFLP）对78例腰椎椎间盘退行性疾病（DDD）（腰椎DDD组）及79例非腰椎DDD的健康体检者（对照组）的外周血进行VDR基因TaqⅠ多态性检测,分析2组间基因型和等位基因的频率分布;研究其中小于45岁者基因型及基因频率分布与椎间盘退变程度的关系。结果腰椎DDD组基因型分布：TT 96.2%（75/78）,Tt 3.8%（3/78）;对照组TT 81.0%（64/79）,Tt 19.0%（15/79）。其中TT基因型分布在2组中的差异有统计学意义（P〈0.05）。腰椎DDD组与对照组等位基因T分布频率分别为98.1%（153/156）和90.5%（143/158）,t分别为1.9%（3/156）和9.5%（15/158）,差异有统计学意义（P〈0.05）;在MRI分组中VDR基因TaqⅠ酶切位点的基因型和等位基因频率在组中分布差异有统计学意义（P〈0.05）。结论 VDR基因TaqⅠ多态性与福建地区汉族人群腰椎间盘退行性变发生有一定关系。     

北方汉族人群维生素D受体基因BsmⅠ位点多态性与前列腺癌易感性的相关性分析

目的 :研究低发病的中国汉族人群维生素D受体基因 (VDRG)BsmⅠ 位点单核苷酸多态性 (SNP)与前列腺癌的关系 ,探讨不同种族前列腺癌发病的基因差异。　方法 :收集中国北方地区汉族人群 10 3例前列腺癌病人及10 6例健康对照者外周血标本 ,应用变性高效液相色谱 (DHPLC)检测VDRG第 8内含子BsmⅠ多态位点 ,并对该位点SNP分布进行分析。　结果 :BsmⅠ 多态位点bb、Bb、BB基因型和等位基因在北方地区汉族前列腺癌病人及对照者中的分布频率差异无显著性 (P >0 .0 5 ) ,基因型分布频率分别为 92 .2 3%、7.77%、0和 94.34 %、5 .6 6 %、0 ;等位基因B、b分别为 3.88%、96 .12 %和 2 .91%、97.0 9%,而与高发病人群的分布相比有显著不同。　结论 :VDRGBsmⅠ多态性在低发病的中国汉族人群与前列腺癌无相关 ,其分布与高发病人群有明显差异 ,提示VDRGBsmⅠ多态性可能是前列腺癌发病种族差异的原因之一。     

北方汉族人群维生素D受体基因Bsm I位点多态性与前列腺癌易感性的相关性分析

目的 :研究低发病的中国汉族人群维生素D受体基因 (VDRG)BsmⅠ 位点单核苷酸多态性 (SNP)与前列腺癌的关系 ,探讨不同种族前列腺癌发病的基因差异。　方法 :收集中国北方地区汉族人群 10 3例前列腺癌病人及10 6例健康对照者外周血标本 ,应用变性高效液相色谱 (DHPLC)检测VDRG第 8内含子BsmⅠ多态位点 ,并对该位点SNP分布进行分析。　结果 :BsmⅠ 多态位点bb、Bb、BB基因型和等位基因在北方地区汉族前列腺癌病人及对照者中的分布频率差异无显著性 (P >0 .0 5 ) ,基因型分布频率分别为 92 .2 3%、7.77%、0和 94.34 %、5 .6 6 %、0 ;等位基因B、b分别为 3.88%、96 .12 %和 2 .91%、97.0 9%,而与高发病人群的分布相比有显著不同。　结论 :VDRGBsmⅠ多态性在低发病的中国汉族人群与前列腺癌无相关 ,其分布与高发病人群有明显差异 ,提示VDRGBsmⅠ多态性可能是前列腺癌发病种族差异的原因之一。     

Nuclear Factor Erythroid-2-related Factor 2 Gene Polymorphisms in Vitiligo

BackgroundOxidative stress is now one of the accepted theories of vitiligo development. Nuclear factor erythroid-2-related factor 2 (Nrf2) regulates the expression of antioxidant proteins.ObjectiveThis work aimed to evaluate the association of Nrf2 gene polymorphisms with the susceptibility to vitiligo among a sample of Egyptian patients with vitiligo.MethodsThis case-control study included 100 patients with vitiligo and 50 healthy matched volunteers serving as a control group. Genotyping was carried out by real-time polymerase chain reaction.ResultsThe frequencies of TT, CT, and combined (TT+CT) genotypes and the T allele of Nrf2 (rs35652124) were significantly increased in the studied patients with vitiligo relative to the healthy controls (p<0.001, p=0.012, p<0.001 and p<0.001, respectively). There was a nonsignificant difference between patients and controls regarding Nrf2 (rs6721961) genotypes. However, the T allele of Nrf2 (rs6721961) was significantly predominant in the studied patients compared to in the controls (p=0.029). Among the studied criteria, the T allele of Nrf2 (rs6721961) was predominant in patients with a marginal type of repigmentation (p=0.022), while the G allele of the same single-nucleotide polymorphism was associated with a higher body mass index value (p=0.034). One hundred percent of patients with vitiligo with the Nrf2 (rs6721961) GT genotype had a progressive disease course (p=0.015).ConclusionNrf2 (−617 T/G) and (−653 T/C) polymorphism might play a role in patient susceptibility to vitiligo and modify the clinical presentation of the disease.     

Human leukocyte antigen DRB1 alleles predict risk and disease progression of immunoglobulin A nephropathy in Han Chinese

The role of human leukocyte antigen (HLA) class II polymorphisms in the pathogenesis and progression of primary immunoglobulin A nephropathy (pIgAN) is unclear. This study aimed to explore the relationship of HLA-DRB1 alleles with the susceptibility and disease progression of pIgAN in Han Chinese. A PCR-based genotyping technique was used to detect HLA-DRB1 alleles in 139 patients with pIgAN and 143 healthy subjects. A total of 37 HLA-DRB1 alleles were detected, of which 30 were found in pIgAN patients and 29 in healthy subjects. In pIgAN patients, the frequencies of HLA-DRB1*140501 (belonging to DR*14) were significantly increased, while the frequencies of HLA-DRB1*070101 (belonging to DR*7) were significantly reduced compared with the healthy individuals. Further stratification analysis revealed that the frequencies of HLA-DRB1*030101 in pIgAN patients with normal renal function were significantly higher than those in patients with renal dysfunction. These findings suggest that HLA-DRB1 polymorphisms are related to the occurrence and disease progression of pIgAN patients in Han Chinese, with HLA-DRB1*140501 being a susceptible allele and HLA-DRB1*070101 a resistant allele. HLA-DRB1*030101 may serve as a predictor of disease progression and renal damage of pIgAN in Han Chinese. Further studies are warranted to explore the immunological mechanisms for the genotype-disease phenotype relationship.     

Vitamin D Receptor Gene Bsm I polymorphism and the susceptibility to prostate cancer in North China Han population

Objective: To study the Bsm I single nucleotide polymorphism (SNP) of vitamin D receptor gene (VDRG) in low-risk Chinese Han population and its relationship to the susceptibility to prostate cancer (PCa). Methods: One hundred and three PCa patients and 106 normal controls from North China Han population were enrolled. Blood samples were obtained and genotyped for Bsm I SNP by denaturing high performance liquid chromatography (DHPLC) methods. Results: There was no significant difference in the distribution of genotype and allele between the PCa patients and the normal controls (P>0.05). The frequencies for the bb, Bb and BB genotypes in PCa patients and normal controls were 92.23%/94.34 %, 7.77 %/5.66 %, and 0/0, respectively. The frequencies for B and b allele were 3.88 % and 96.12 %, and 2.91 % and 97.09 %, respectively. Conclusion: There is no significant relationship between the VDRG polymorphism and PCa in North China Han population. The distribution of VDRG Bsm I SNP varies in different ethnic popul     

多聚ADP核糖聚合酶1Val762Ala基因多态性与胃癌易感性的关系

目的 研究多聚ADP核糖聚合酶1(PARP-1)的Val762Ala(T2444C)在中国西北甘肃地区汉族人群胃癌患者和健康对照者中的基因型分布频率,并探讨其与胃癌发病风险的关系.方法 采用PCR-限制性片段长度多态性方法,对138例胃癌患者和110例健康体检者(排除肿瘤和消化系统疾病)进行病例-对照的基因分型研究.以logistic回归和X2检验计算比值比(OR)及其95%可信区间(CJ).结果 Val762Ala(T2444C)的Ala等位基因的分布频率在胃癌组(11.5%)明显高于对照组(4.5%),OR值为3.012(95% CI:1.054～8.603,P=0.033).结论 PARP-1 Val762Ala(T2444C)遗传变异与胃癌易感性相关,PARP-1762Ala等位基因型(2444CC)是胃癌的一个易感性标志.     

中国汉族深静脉血栓形成患者与组织因子途径抑制物基因多态性的关系

目的探讨组织因子途径抑制物(TFPI)基因变异与中国汉族深静脉血栓形成(DVT)患者的相关性。方法采用聚合酶链反应单链构象多态性分析及DNA测序,对62例DVT患者和50例正常汉族人进行TFPI基因序列分析。结果8号内含子中发现一个C/T多态位点,等位基因频率为86.6%和13.4%,病例组与对照组比较无统计学差异;5号内含子41位发现一个单碱基“G”插入,病例组中有4例(6.5%)与对照组比较差异无统计学意义(P>0.05)。结论TFPI基因可能不是中国汉族人DVT的主易感基因;5号内含子中单核苷酸“G”插入有深入研究价值。     

Association of cadherin23 single nucleotide polymorphism with age-related hearing impairment in han chinese

Objective Genetic variation of cadheri23 (cdh23; 753G>A in exon 7) has been implicated with age-related hearing impairment (ARHI) in mice. This study aimed to test the association of the CDH23 tag single nucleotide polymorphism (SNP) in intron 7 with ARHI in Han Chinese. Study Design Individual cohort study. Setting Tertiary medical center. Subjects and Methods A total of 1175 Han Chinese subjects were divided into the case group (n = 310, 26% with poorest hearing) and the control group (n = 308, the 26% with best hearing) according to the Z(high) score converted from the original frequency-specific hearing thresholds. The CDH23 SNP locus (rs7087735: C/T) in intron 7 (coordinate: 72996763) shown in the HapMap was genotyped with correlation to the hearing phenotype. Results The genotype distributions of CDH23 (CC/CT/TT) were not significantly different between the case and control group (P = .489). Compared with genotype CC, the odds ratios of the genotypes CT and TT for ARHI were not significantly different after adjustment for other environmental factors (P = .299 for CT; P = .610 for TT). Conclusions Despite that the Ahl allele of Cdh23 had been implicated with ARHI in mice, we found no positive association of the CDH23 tag SNP in intron 7 with ARHI in Han Chinese.     

Proteasome Subunit Beta Type-8 (PSMB8) Gene Polymorphisms in Vitiligo: A Possible Predictor of Auditory Involvement

IntroductionProteasome subunit beta type-8 (PSMB8) is a protein that contributes to the complete assembly of 20S proteasome complexes, which play a role in the pathogenesis of vitiligo.ObjectiveThe study aimed to evaluate the association between PSMB8 gene polymorphisms with vitiligo to assess its clinical significance among a sample of Egyptian patients with vitiligo.MethodsGenomic DNA was isolated from blood samples of 100 patients with vitiligo and 100 control subjects, and detection of PSMB8 polymorphisms was done by real-time PCR. Data analysis was carried out for the entire cohort. Statistics were performed using software. Audiological evaluation was performed, including pure-tone audiometry, extended high-frequency audiometry, transient evoked otoacoustic emissions, and auditory brainstem response.ResultsThere was a significant difference between PSMB8 genotypes and alleles distribution in patients and control groups. Ten percent of the study sample had sensorineural hearing loss. The patients with hearing loss were significantly older (P=0.0002), had significantly later age of onset (P=0.0007), longer duration (P=0.0021), higher body mass index (BMI) (P=0.045), and higher vitiligo area scoring index (VASI) scores (P=0.0015). All patients had extensive forms of vitiligo (generalized and universal). Regarding the VIT rs2071543 polymorphism, all of the patients with hearing loss were carrying the CA and AA genotypes. None of the patients carried the reference genotype, CC. The A allele of VIT rs2071543 was significantly associated with hearing affection (P=0.024).ConclusionIn our study, PSMB8 polymorphism was associated with the susceptibility to develop vitiligo and appeared to have clinical significance among the studied group of patients. Factors predicting auditory abnormalities should be further studied for early detection and management.