GULP1基因多态性与精神分裂症及其认知功能的相关性研究

目的探讨GULPl基因多态性与精神分裂症及认知功能的关系。方法采用聚合酶链反应限制性片段长度多态性（PCR—RFLP）的方法检测86例精神分裂症患者（观察组）和72名健康人（对照组）的GULPI基因SNPrs2004888多态性;采用韦氏记忆量表（WMS）和威斯康辛卡片分类测验（WCST）评估两组记忆功能和执行功能,并用PANSS量表评定患者的临床症状。观察两组GULPl基因多态性及认知功能的差异。结果两组GULPl基因SNPrs2004888多态性的基因型和等位基因频率差异有统计学意义（x2=35．71、32．21,均P〈0．05）;观察组各基因型组问韦氏记忆量表的理解记忆评分差异有统计学意义（P〈0．05）;G／G与T／T基因型患者比较,错误数、持续错误数和分类个数差异有统计学意义（P〈0．05）。结论GULPl基因SNPrs2004888多态性频度增高与精神分裂症有一定的关联,且与患者的认知功能相关。     

ADPRT基因rs1136410位点多态性与苏北地区汉族人群非小细胞肺癌发生的相关性分析

目的:探讨DNA修复基因聚腺苷酸二磷酸核糖转移酶(ADPRT)基因rs1136410位点多态性与苏北地区汉族人群非小细胞肺癌(NSCLC)发生的相关性。方法:选取2015年11月-2018年12月于徐州医科大学附属医院就诊的苏北地区汉族原发性NSCLC患者283例,作为NSCLC组;选择同期体检的健康者210例作为对照组。采用聚合酶链反应-限制性片段长度多态性方法检测各受试者ADPRT基因rs1136410位点的基因型,采用Logistic回归模型评价位点多态性及其与吸烟交互作用对NSCLC发生的影响。结果:两组受试者性别、年龄比较,差异均无统计学意义(P>0.05);而NSCLC组吸烟者的比例显著高于对照组(P<0.05)。共检出ADPRT基因rs1136410位点TT、TC、CC等3种基因型。其中,对照组受试者TT、TC、CC型频率分别为41.9%、44.8%、13.3%,T、C等位基因频率分别为64.3%、35.7%;NSCLC组患者TT、TC、CC型频率分别为21.6%、50.2%、28.2%,T、C等位基因频率分别为46.6%、53.4%。两组受试者各基因型频率均符合Hardy-Weinberg平衡(P>0.05),但基因型及等位基因频率的组间差异明显(P<0.05)。与TT型个体比较,TC、CC型个体发生NSCLC的风险分别增加了1.179、3.122倍[比值比(OR)分别为2.179、4.122,95%置信区间(CI)分别为(1.435,3.309)、(2.401,7.075),P<0.05]。与TT型不吸烟个体比较,TC、CC型不吸烟个体发生NSCLC的风险分别增加了0.371、1.328倍[OR分别为1.371、2.328,95%CI分别为(0.927,3.428)、(1.249,4.622),P<0.05],TC、CC吸烟个体发生NSCLC的风险分别增加了0.928、2.182倍[OR分别为1.928、3.182,95%CI分别为(1.257,2.957)、(1.760,5.754),P<0.05]。结论:ADPRT基因rs1136410位点突变是我国苏北地区汉族人群罹患NSCLC的危险因素,且吸烟可进一步增加该位点突变个体发生NSCLC的风险。     

哮喘易感基因ORMDL3单核苷酸多态性位点rs7216389与中国人群特应性皮炎及其临床表型的相关性

目的 探讨哮喘易感基因ORMDL3的单核苷酸多态性位点rs7216389与中国人群特应性皮炎(AD)及其临床表型的相关性.方法 采用聚合酶链式反应-限制性片段长度多态性的方法,对592例AD患者(AD组)和509例健康人群(对照组)的ORMDL3多态位点rs7216389进行基因分型和分析.结果 两组rs7216389的基因型频率和等位基因型频率均无显著差异.女性群体中,rs7216389基因型分布在两组之间有显著差异(P＜0.05),与AD诊断显著相关.rs7216389与AD同时伴发哮喘和鼻炎显著相关,基因型CC在AD同时伴发哮喘和鼻炎病例中的频率显著增高(P＜0.05).rs7216389与AD发病年龄显著相关,基因型TT的AD患者发病年龄显著低于基因型TC或CC的AD患者(P＜0.05).结论 哮喘易感基因ORMDL3的多态位点rs7216389与中国人群,尤其是女性AD及其临床表型相关.基因型CC可能是AD同时伴发哮喘和鼻炎的风险因素,基因型TT则可能与AD早期发病相关.     

白细胞介素-35基因多态性与冠心病患者认知功能障碍的相关性研究

目的 探讨白细胞介素（IL）-35基因多态性与冠心病患者认知功能障碍发生风险的相关性。方法 选择2015年2月—2016年10月在广西壮族自治区人民医院心血管内科首次诊断为冠心病的患者349例,均使用简易精神状态检查量表（MMSE）进行认知功能评估,按评估结果分为认知功能正常组（对照组）205例和认知功能损伤组（病例组）144例。使用Sequenom Mass Array系统对IL-35单核苷酸多态性（SNPs）位点（rs582054、rs2243115、rs428253、rs583911、rs568408和rs4740）进行基因型分析。使用酶联免疫吸附实验（ELISA）检测血浆IL-35水平。其他相关指标均由广西壮族自治区人民医院检验科按标准流程进行检测。采用Logistic回归模型探讨IL-35 SNPs与冠心病患者认知功能障碍发生风险的相关性。结果 2 组间血浆 IL-35 水平差异无统计学意义［42.26（17.19,203.06）ng/L vs.40.60（22.69,105.65）ng/L,Z=0.384,P＞0.05］。Logistic 回归分析结果显示,校正吸烟史、饮酒史、高血压、糖尿病病史、认知功能障碍家族史、年龄、丙氨酸转氨酶（ALT）及空腹血糖水平等因素后,并未发现 IL-35 多态性位点（rs582054、rs2243115、rs428253、rs583911、rs568408和rs4740）与冠心病患者认知功能障碍发生风险存在相关性。结论 IL-35基因SNPs与冠心病患者认知功能障碍发生风险之间不存在相关性,将来仍需进一步扩大样本量并对其可能的机制进行探讨。     

CD36 rs3211956和rs7755单核苷酸多态性与早发冠心病的相关性

目的 探讨早发冠状动脉粥样硬化性心脏病(CHD)的危险因素,及CD36基因rs7755和rs3211956单核苷酸多态性(SNP)与早发CHD的相关性。方法 连续筛选冠状动脉造影证实的早发冠脉严重三支病变者(病变组)102例及冠脉造影正常者(正常组)72例,对比2组CHD的传统危险因素,并用质谱法检测所有入选者CD36 rs7755和rs3211956位点基因型,分析早发CHD的独立危险因素。结果 传统危险因素中,男性、糖尿病、高血压、高低密度脂蛋白胆固醇(LDL-C)及低高密度脂蛋白胆固醇(HDL-C)是早发CHD的独立危险因素。病变组中rs3211956的GT基因型分布低于正常组(χ2=8.042,P=0.005),而TT基因型分布高于正常组(χ2=6.191,P=0.014);TT基因型者较含G等位基因者的体质指数(BMI)水平增高(P=0.037)。病变组rs7755的G等位基因的频率高于正常组(χ2=3.636,P=0.047);GG基因型的BMI水平高于A等位基因携带者(P<0.001),而HDL-C水平低于另两种基因型者(P<0.001)。Logistic回归分析显示在分别调整了混杂因素后,rs3211956基因型GG、TT及rs7755基因型GG、GA均为早发CHD的独立危险因素。结论 CD36 rs3211956、rs7755的SNP可能是致早发CHD的独立危险因素,且可能通过影响BMI和HDL-C而影响早发CHD的发生。     

精神分裂症患者认知功能的研究

精神分裂症患者认知功能的损害是其回归社会的重要影响因素。认知心理学为认知功能的评估提供了四方面的研究方法和途径。本综述以认知功能的评估方法为线索,从各种量表测查到返回抑制评定到功能核磁共振成像检查,再到成套的认知评估系统,使认知功能的研究越发有针对性。对精神分裂症患者认知功能障碍与其性别、病程、用药、阴性症状的关系进行了综述。慢性精神分裂症患者存在全面的认知功能损害,其认知功能损害无明显性别差异。使用非典型抗精神病药治疗的精神分裂症患者合并丁螺环酮组的认知功能与安慰剂组比较,仅在注意力方面有改善,且研究组在前3个月改善注意力的优势明显。精神分裂症患者长期住院治疗比非住院的患者或短时间住院治疗的患者认知损害严重。目前在治疗精神疾病认知功能损害方面较为新颖的治疗手段是关注5-HT1A受体。精神分裂症患者阴性症状严重的认知功能损害明显。     

ApoA5基因rs651821位点多态性与侗族人群代谢综合征的关系研究

目的 探讨载脂蛋白A5(ApoA5)基因rs651821位点多态性与代谢综合征(MS)的关系.方法 选取2017年6月至2018年6月在湖南省通道侗族自治县某卫生院就诊的160例MS患者作为MS组,同时选取145例健康体检者作为对照组.比较2组基因型和等位基因频率分布情况,分析ApoA5基因rs651821位点单核苷酸...     

精神分裂症患者磷酸丝氨酸氨基转移酶1基因多态性与利培酮疗效关联性研究

目的观察精神分裂症患者磷酸丝氨酸氨基转移酶1基因多态性与利培酮疗效的相关性。方法精神分裂症患者158例,按隔日加量法则,利培酮逐渐加至治疗剂量（2～6 mg&#8226;d－1）,根据不良反应情况调整剂量,平均治疗量 （3.82±0.95） mg&#8226;d－1。出现药物不良反应时采取对症治疗、减量或换药治疗。观察6周,在第0,6周评定阳性与阴性量表评分（PANSS）。采用聚合酶链反应扩增及单核苷酸多态性的分子生物学技术测定磷酸丝氨酸氨基转移酶1基因的rs69287125、rs137824326多态性分型,比较不同分型患者的利培酮疗效。结果rs69287125和rs137824326位点基因型和等位基因频数在男女患者中差异无统计学意义（P＞0.05）;治疗6周后,rs69287125位点PANSS总分、阳性因子分、阴性因子分在三个不同基因型中差异有统计学意义（P＜0.05）,A/A基因型分值最高;rs137824326位点PANSS总分、阳性因子分、阴性因子分、一般精神病理分在3个不同基因型中差异有统计学意义（P＜0.05）,A/A基因型分值最高。 结论精神分裂症患者磷酸丝氨酸氨基转移酶1基因多态性与利培酮疗效存在关联。     

The FNTB promoter polymorphism rs11623866 as a potential predictive biomarker for lonafarnib treatment of ovarian cancer patients

Aim

Despite promising preclinical findings regarding clinical utility of farnesyltransferase inhibitors (FTI), such as lonafarnib, success of clinical trials is limited. A multicentre AGO-OVAR-15 phase II trial reported an unfavourable effect of lonafarnib on the outcome of patients with advanced ovarian cancer. This study was performed as a genetic subgroup analysis of the AGO-OVAR-15 trial, and investigated the utility of the promoter polymorphism rs11623866 of the farnesyltransferase ß-subunit gene (FNTB) in predicting the clinical effectiveness of lonafarnib.

Methods

The influence of rs11623866 (c.-609G > C) on FNTB promoter activity was investigated by electrophoretic-mobility-shift assay, luciferase-reporter assay and RT-qPCR. A total of 57 out of 105 patients from the AGO-OVAR-15 trial, treated with carboplatin and paclitaxel ± lonafarnib, was genotyped for rs11623866 by restriction fragment length polymorphism analysis. Genotype-dependent survival analysis was performed by Kaplan–Meier analysis.

Results

The presence of the G allele was associated with increased FNTB promoter activity compared with the C allele. An unfavourable effect of lonafarnib was limited to patients carrying a GG genotype (HR_PFS 6.2, 95%CI = 2.01, 19.41, P = 0.002; HR_OS 9.6, 95%CI = 1.89, 48.54, P = 0.006). Median progression free survival (PFS) for patients with the GG genotype in the lonafarnib treated arm was 10 months, whereas median PFS without FTI-treatment was 40 months. Median overall survival (OS) in the lonafarnib-treated group was 19 months, whereas median OS was not reached in the untreated group.

Conclusions

Discrepancies between preclinical success and clinical failure may be due to the patients'' genetic variability of FNTB. Therefore, our results may encourage retrospective evaluation of FNTB polymorphisms in previous FTI studies, especially those reporting positive FTI response.     

BDNF rs 6265 polymorphism and COMT rs 4680 polymorphism in deficit schizophrenia in Polish sample

BackgroundDeficit schizophrenia (DS) is distinguished from the group of schizophrenic psychoses based on the presence of primary negative symptoms. It differs from nondeficit (NDS) forms of schizophrenia in dimensions such as risk factors, family history, course of illness and neurobiological differences. The aim of the study was assessment of a potential association of the investigated polymorphisms of the brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT) genes with the deficit syndrome in schizophrenia.MethodsAcohort of 200 patients with schizophrenia (81 DS and 119 NDS subjects) and a group of 100 control subjects matched for ethnicity, sex and age were recruited. Somatic and psychometric assessment were conducted as well as structured interview about the influence of adverse biological, family and social factors. Genetic analysis of the BDNF (Val66Met) rs6265 and the COMT (Val158Met) rs4680 polymorphisms was performed.ResultsWe found significant differences between DS and NDS in rs4680 COMTgenotype distribution: more homozygous Val/Val were found (31 vs. 17%) in the NDS compared to the DS subgroup. No associations were found between the investigated polymorphisms of the BDNF gene and the presence of schizophrenia either in DS and NDS subgroups.ConclusionThe analysis of the COMT rs4680 polymorphism in the present DS and NDS study shows that some genetic factors may be relevant in analyzing the reasons for the differentiation of schizophrenic subtypes.     

Polymorphism of Prodynorphin promoter is associated with schizophrenia in Chinese population

AIM: To investigate the correlation between single nucleotide polymorphisms (SNPs) of functional candidate gene Prodynorphin (PDYN) and schizophrenia. METHODS: SNPs in the promoter and exon regions of PDYN were screened and genotyped for association study in a cohort of Chinese Han schizophrenia cases and controls. RESULTS: Two SNPs PDYN-1576C>T and PDYN-946C>G were identified in the promoter region but PDYN-946C>G showed significant differences of allele distribution (x2=6.15, P=0.013) and genotype distribution (x2=6.87, P=0.032) between schizophrenic and control subjects. CONCLUSION: PDYN-946C>G polymorphism demonstrated an association with population susceptibility to schizophrenia (P<0.05).     

新疆地区哈萨克族慢性阻塞性肺疾病易感性与ADAM33 基因多态性的关系

目的探究整合素-金属蛋白酶33（ADAM33）基因F+1、S2、T1、ST+5 位点多态性与新疆地区哈萨克族慢性阻塞性肺疾病（COPD）易感性的关系。方法选择193 例对照组及197 例COPD 病例组,提取外周血标本DNA,运用SNaPshot SNP 分型技术检测ADAM33 基因各位点多态性。结果病例组与对照组F+1 位点的基因型及等位基因频率分布比较差异有统计学意义（P<0.05）。病例组中,F+1 位点CC、CT、TT 3 种基因型肺功能相关指标第1 秒用力呼气容积（FEV1）预计值（%）、FEV1/用力肺活量（FVC）比较差异无统计学意义。病例组与对照组S2、ST+5、T1 位点的基因型及等位基因频率分布比较差异无统计学意义;F+1、S2 位点进行单体型分析显示Hap1（CC）在对照组和病例组分布差异有统计学意义（P < 0.05）,且OR < 1,表明此单体型可能降低发生COPD 的风险;Hap3（TC）在对照组和病例组分布差异有统计学意义（P < 0.05）,且OR > 1,表明此单体型可能增加了COPD 发病的风险;Hap2（TG）、 Hap4（CG）单体型在2 组间分布差异无统计学意义;病例组及对照组T1、ST+5 位点3 种单体型比较差异无统计学意义。结论ADAM33 基因F+1 位点多态性可能与新疆哈萨克族人群COPD 的发生有关。     

Association between PLA2G12A polymorphism and patients with schizophrenia in a southern Chinese Han population

Background

Elevated phospholipase A2 (PLA2) activity is reported to be involved in the development of schizophrenia. Further study revealed an association between PLA2 groups XIIA (PLA2G12A) polymorphism and patients with schizophrenia in a northeast Chinese Han population.

Objective

This study will further examine whether PLA2G12A rs3087494 polymorphism is associated with patients with schizophrenia in a southern Chinese Han population.

Methods

This polymorphism was genotyped in 438 patients with schizophrenia (diagnosed according to Diagnostic and Statistical Manual of Mental Disorders‐IV) and 876 healthy controls using a case–control design. Demographic and clinical data were collected in all subjects.

Results

The allele and genotype frequencies of PLA2G12A rs3087494 polymorphism significantly differed between groups (both, p < .001). These differences still were significant by adjusting for sex and age. However, there was no difference in age at onset among 3 genotype groups in patients with schizophrenia by adjusting for the variables (F = 0.22, p = .80). Stepwise multivariate regression analysis showed that this polymorphism was not associated with age at onset in patients with schizophrenia (β = .008, t = .07, p = .94).

Conclusions

Our results indicated that even though PLA2G12A rs3087494 polymorphism did not influence age at onset in patients with schizophrenia, it may play an important role in the susceptibility to schizophrenia in a southern Chinese Han population.     

Association study between HTR2A rs6313 polymorphism and early response to risperidone and olanzapine in schizophrenia patients

Antipsychotic drugs are the preferred choice for schizophrenia treatment; however, response is highly variable. In the context of the search for predictors of antipsychotic treatment effectiveness, the evaluation of response within 2 weeks has been indicated to predict long-term outcome. Moreover, a focus on symptomatological domains could be helpful to better characterize antipsychotic response, identifying more specific predictors. Pharmacogenetic studies have indicated a role for rs6313 in the serotonin receptor gene HTR2A in affecting response to antipsychotics, with heterogeneous results. With the aim to test for the first time the application of a dimensional approach for the evaluation of early response, we carried out a genetic association study between rs6313 and antipsychotic response in two groups of schizophrenia patients in monotherapy with risperidone (n = 121) and olanzapine (n = 100). Patients were evaluated at the baseline and after 1 and 2 weeks of treatment. When comparing early responders versus early nonresponders, no association was detected for the two drugs separately, whereas by taking into consideration the two drugs together it was observed that carriers of the T allele had a higher response probability compared to noncarriers. Considering 2-week improvements, changes in PANSS total scores, subscores and in PANSS Emsley's symptomatological dimensions were associated with rs6313 for both risperidone and olanzapine. Moreover, the repeated measures analysis indicated an association of rs6313 with the disorganized thought dimension for risperidone, and with the depressive and anxiety dimensions for olanzapine. These data add support to the hypothesis that the HTR2A gene is involved in antipsychotic treatment outcome.     

rs7968606 polymorphism of ANKS1B is associated with improvement in the PANSS general score of schizophrenia caused by amisulpride

A recent genome‐wide pharmacogenomics study showed that the rs 7968606 single‐nucleotide polymorphism (SNP) of the ankyrin repeat and sterile alpha motif domain‐containing protein 1B (ANKS1B ) gene approached the threshold of statistical significance. The aim of this study was to determine the association between the rs 7968606 SNP of ANKS1B and the treatment response to amisulpride in schizophrenia patients. In total, 154 participants were enrolled from six university hospitals in Korea. All the subjects were interviewed before and after 6 weeks of amisulpride treatment with the aid of the positive and negative syndrome scale and the clinical global impression–severity scale. Genotyping for the rs 7968606 SNP of ANKS1B was performed in 101 subjects. Both the decrease (t  = −2.067, p  = 0.041) and improvement rate (t  = −1.990, p  = 0.049) in the positive and negative syndrome scale general score differed significantly between T‐allele carriers and noncarriers of this polymorphism after 6 weeks of amisulpride treatment. To the best of our knowledge, this is the first genetic association study of the relationship between the rs 7968606 SNP of ANKS1B and the response of schizophrenia patients to treatment with amisulpride. Future larger‐scale studies involving more SNPs of ANKS1B will improve the understanding of the pharmacogenetics underlying the treatment responses to amisulpride.     

ORAI1基因rs3741596单核苷酸多态性与川崎病的关系

摘要： 目的 探讨钙释放激活钙调节蛋白1 （CRACM1/ORAI1） 基因rs3741596位点单核苷酸多态性 （SNP） 与川崎病 （KD） 易感性及KD并发冠状动脉病变 （CALs） 是否相关。方法 将确诊的46例KD患儿 （病例组） 和25例健康儿童（对照组） 纳入本研究, 并根据是否出现CALs将病例组分为CAL组 （20例） 和无CAL （NCAL） 组 （26例）。应用聚合酶链反应 （PCR） 技术联合基因直接测序技术检测所有研究对象ORAI1基因rs3741596位点SNP, 并进行统计学分析。结果 所有研究对象均检测到ORAI1基因rs3741596位点SNP, 其基因型分布及等位基因频率在病例组及对照组间差异无统计学意义 （χ2 分别为0.712和0.499, 均P＞0.05）, 而在CAL组和NCAL组间差异有统计学意义 （χ2 分别为 6.524 和 6.891, 均 P＜0.05）; 携带 G 等位基因使 KD 患儿并发生 CALs 的危险性增加（OR=5.444, 95%CI： 1.386~ 21.380）。结论 ORAI1基因rs3741596位点SNP可能与KD易感性无相关性, 但与KD并发CALs易感性相关。     

PPARD rs2016520 polymorphism affects repaglinide response in Chinese Han patients with type 2 diabetes mellitus

Repaglinide is a short‐acting insulin secretagogue, which often results in considerable interindividual variability in therapeutic efficacy when widely used in a clinical setting. Among various reasons under discussion is genetic polymorphism, especially the genes related to insulin secretion and resistance. Recent studies have described the importance of PPARD in regulating the secretion and resistance of insulin. However, little is known about the impacts of PPARD genetic polymorphism on the efficacy of repaglinide. Therefore, the current study was designed to investigate the associations of PPARD rs2016520 polymorphism with type 2 diabetes mellitus (T2DM) susceptibility and repaglinide therapeutic efficacy in Chinese Han T2DM patients. A total of 338 T2DM patients and 200 healthy subjects were genotyped for PPARD rs2016520 polymorphism by polymerase chain reaction–restriction fragment length polymorphism assay. A total of 84 patients with the same genotypes of CYP2C8*3 139Arg and OATP1B1 521TT were randomized to orally take repaglinide for 8 weeks. Then the pharmacodynamic parameters of repaglinide and biochemical indicators were determined before and after repaglinide treatment. No significant difference was found in either allelic frequency (P = 0.298) or genotype distribution (P = 0.151) of PPARD rs2016520 between T2DM patients and healthy subjects. However, T2DM patients carrying genotype TC showed a significantly lower increase in postprandial serum insulin (mU/L) than those with wild‐type TT (P < 0.05). These findings suggest that PPARD rs2016520 polymorphism might influence the therapeutic effect of repaglinide rather than T2DM susceptibility in Chinese Han T2DM patients.