精神分裂症断裂基因1(DISC1)多态性与精神分裂症的关联研究

目的:探讨精神分裂症断裂基因1(DISC1)与精神分裂症及临床症状的遗传关联.方法:应用病例对照关联研究设计,采用聚合酶链式反应-限制性片断长度多态性(PCR-RFLP)方法:分析466例精神分裂症患者和551例正常对照者DISC1基因2个单核苷酸多态性(SNP)位点与精神分裂症的关联.并采用阳性和阴性症状量表(PANSS)评估患者的临床症状,进一步分析PANSS因子分与DISC1多态性的关联.结果:DISC1基因的两个多态性位点rs821597(等位基因A>G,χ2=6.009,P=0.014;基因型:χ2=6.505,P=0.039)和rs821616(等位基因A>T,χ2=7.063,P=0.008;基因型:χ2=6.928,P=0.031)均与精神分裂症显著关联.由上述2个SNPs组成的多个单体型均与精神分裂症关联[如AT(χ2=7.065,P=0.008,OR=1.42,95%CI=1.10～1.83)和GA(χ2=6.009,P=0.014,OR=0.80,95%CI=0.68～0.96)].上述2个SNPs组成的风险单体型AT间PANSS量表各因子分差异均无统计学意义(均P>0.05).结论:DISC1基因多态性与精神分裂症显著关联,但与精神分裂症症状无关联.     

B7-H4基因多态性与乳腺浸润性导管癌预后的相关性研究

目的探讨B7-H4基因rs10754339、rs10801935和rs3738414等单核苷酸多态性（SNP）位点多态性与黑龙江省妇女乳腺浸润性导管癌预后的相关性。方法取280例乳腺浸润性导管癌患者的外周血提取基因组DNA,利用聚合酶链式反应限制性片段长度多态性（PCR．RFLP）技术进行B7．H4单核苷酸多态性检测,引用统计学软件分析基因多态性与患者临床指标（包括肿瘤大小,淋巴结转移,以及雌激素受体、孕激素受体和P53基因的表达）间的关系（卡方检验计算P值）,进而确定该基因与黑龙江省汉族妇女乳腺癌预后的相关性。结果B7-H4基因的rs10754339中,AA和AG基因型发生频率在雌激素受体表达阳性和阴性患者中有统计学差异（Х^2=4．06,P〈0．05;Х^2=3．97,P〈0．05）,AA基因型和G等位基因发生频率在孕激素受体表达阳性和阴性患者中有显著差异（Х^2=4．74,P〈0．05;Х^2=5．30,P〈0．05）。rs10801935中,AA基因型和C等位基因发生频率在孕激素受体表达阳性和阴性患者中有显著差异（Х^2=5．36,P〈0．05;Х^2=5．90,P〈0．05）,而AC基因型发生频率在P53基因表达阳性和阴性患者中有显著差异（Х^2=5．82,P〈0．05）。结论B7-H4基因多态性与乳腺浸润性导管癌患者雌激素受体,孕激素受体及P53基因的表达有关联,与乳腺癌患者的预后有一定相关性。     

G蛋白β3亚单位基因C825T多态性与蒙古族原发性高血压的相关性研究

目的探讨G蛋白β3亚单位基因C825T多态性与蒙古族人群原发性高血压患者之间的关系。方法采用Sequenom系统检测分析方法检测124例健康人和143例高血压患者的G蛋白β3亚单位基因C825T多态性。结果（1）蒙古族人群GNB3基因C825T位点CC、CT、TT基因型频率在高血压组和正常血压组分别为0．48、0．41、0．11和0．43、0．47、0．10，差异无显著性（χ^2=0．162，P=0．688；OR：1．176，95％CI 0．533～2．592）；C、T等位基因频率在高血压组和对照组分别为0．69、0．31和0．67、0．33差异无显著性（χ^2=0．094，P=0．759；OR：0．945，95％CI0．657—1．358）。（2）蒙古族人群GNB3基因C825T位点CC、CT、TT基因型频率在单纯收缩压增高组和正常血压组分别为0．57、0．35、0．08和0，43、0．47、0．10．差异无显著性（χ^2=0．733．P=0．392；OR：1．957，95％CI0．623—6．143）；C、T等位基因频率在单纯高血压组和对照组分别为0．74、0．26和0．67、0．33，差异无显著性（χ^2=2．133，P=0．144；OR：0．697，95％CI0．428—1．133）。结论G蛋白β3亚单位基因C825T位点与蒙古族人群原发性高血压的发生可能无关，不是蒙古族人群原发性高血压的遗传标志．     

TPH2基因多态性与重度抑郁发作治疗反应的关系研究CSCD

目的分析TPH2基因多态性与重度抑郁发作（major depressive disorder,MDD）治疗反应之间的相关性。方法收集304例接受抗抑郁药治疗的MDD患者。用MassArray质谱分析法对TPH2基因的3个单核苷酸多态性（rs1007023、rs1023990和rs4570625）进行基因分型。用HAMD-17量表评估基线和治疗1、2、4和6周后的效果。结果共290名受试者完成了研究,其中rs4570625基因多态性与抗抑郁治疗的效果存在显著的相关性,有效组和无效组的基因型、等位基因分布频率差异具有统计学意义（P=0．013,P=0．007）,经错误发现率校正后,上述差异仍具有统计学意义（P=0．039,P=0．021）,治疗有效的患者中等位基因G和GG基因型的频率更高（OR=1．70,95％CI=1．15～2．51;OR=3．34,95％CI=1．40～7．98）。未发现rs1007023和rs1023990基因多态性和抗抑郁药疗效存在相关性（P〉0．05）。结论TPH2基因rs4570625多态性可能与抗抑郁药疗效存在一定的关联。     

G72基因与抑郁症的关联研究

目的探讨抑郁症与G72基因多态性的关系，以及是否有混合家族史的抑郁症其G72基因多态性有无区别。方法应用聚合酶链反应技术分别检测符合《中国精神障碍分类与诊断标准》的100例元混合家族史抑郁症、50例有混合家族史抑郁症、86名正常对照的G72基因的单核苷酸多态性rs947267、rs2181953，并进行关联分析。结果（1）女性无混合家族史抑郁症组与对照组rs947267基因型及等位基因分布频率，差异均有统计学意义（P=0．017、P=0．008），基因型A／A、等位基因A、C的OR值分别为0．300（P=0.010）、0．456（P=0．008）、2．195（P=0．008），而男性差异均无统计学意义（P〉0．05）；（2）不同性别无混合家族史抑郁症组与对照组rs2181953基因型及等位基因分布，差异均无统计学意义（P〉0．05）；（3）不同性别有混合家族史抑郁症组与对照组rs947267、rs2181953基因型及等位基因分布，差异均无统计学意义（P〉0.05）。结论G72基因多态性可能与女性无混合家族史的抑郁症患者存在关联，其中rs947267的C等位基因是危险因子。     

延边地区汉族和韩国人精神分裂症患者脯氨酸脱氢酶 - T1945C基因的多态性

目的：探讨延边汉族和韩国人精神分裂症脯氨酸脱氢酶（PRODH）-1945（T／C）基因多态性患者的相关性。方法：采用Amp-RFLP方法对265例汉族和韩国人精神分裂症患者和192例正常人群的PRODH-1945（T／C）基因的相关性进行研究。结果：PRODH-1945（T／C）基因基因型频率和等位基因频率，在汉族患者和正常人群之间、韩国人患者和正常人群之间均无统计学差异；但不管是患者组还是正常人组，汉族和韩国人之间PRODH-1945（T／C）基因基因型频率（χ^2=6．19，P=0．045，χ^2=6．45，P=0．04）和等位基因频率差异均有显著性（χ^2=5．46，P=0.02，χ^2=5.75，P=0．02），如汉族M等位基因频率均低于韩国人（患者：69．3％／78．4％，正常人：74，5％／84．4％）。结论：延边地区汉族和韩国人之间正常人群和精神分裂症患者的PRODH-1945（T／C）基因的变异，可能与种族差异有一定的相关性。     

精神分裂症与KCNN3基因1137～1140缺失移码突变传递不平衡研究

目的 探讨KCNN3基因1137～1140的4个碱基缺失所致移码突变与精神分裂症的关系。方法 95个核心家系共289名家庭成员，包含107例精神分裂症患者纳入本研究。精神分裂症采用CCMD-Ⅱ-R诊断标准。KCNN3基因1137～1140的4个碱基缺失基因型检测使用PCR技术和限制性内切酶DdeI消化方法。精神分裂症与KCNN3基因1137～1140缺失4个碱基的关联分析采用基于单倍型的单倍型相对风险率和传递／不平衡检验。结果 患者组与正常父母组比较，KCNN3基因1137～1140的4个碱基缺失的基因型频数和等位基因频率分布差异无统计学意义（χ^2=0．253，P〉0．05和χ^2＝0．010，P〉0．05）。基于单倍型的单倍型相对风险分析发现父母传递与不传递给患者的KCNN3基因等位基因之间差异无统计学意义（χ^2=0．042，P〉0．05）。传递不平衡检验结果发现KCNN3基因等位基因传递不存在连锁不平衡（χ^2=3．000，P＝0．0833）。结论 本组研究对象中，KCNN3基因第1外显子1137～1140的4个碱基缺失的发生率少；分析结果提示KCNN3基因第1外显子1137～1140的4个碱基缺失的等位基因与精神分裂症无关联。     

网状内皮素4受体基因多态性与中国汉族精神分裂症关联分析

目的:分析网状内皮素4受体(RTN4R)基因上的5个单核苷酸多态性(SNP)与中国汉族精神分裂症关联,探讨RTN4R基因单核苷酸多态性与精神分裂症易感性的关系。方法:收集符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)诊断的528名偏执型精神分裂症患者,在同一地域招募健康体检者528名作为对照,并采用阳性与阴性症状量表(PANSS)评估234例首次发病患者的临床症状,采用基因分型芯片对RTN4R基因上的5个功能单核苷酸多态性位点进行基因分型,分析多态性与疾病的关联性,以及PANSS因子分与RTN4R多态性的关联。结果:成功检测5个单核苷酸多态性位点的基因型,关联分析显示这些位点基因型和等位基因频率分布病例和对照之间差异无统计学意义。与携带rs696880位点GG基因型患者相比,携带AA基因型患者PANSS阳性分[(23.5±5.6)vs.(25.1±7.6),P0.05]、一般精神病理症状分[(42.6±9.9)vs.(46.0±13.4),P0.05]均较低,携带AA基因型患者发病年龄晚于携带GG型患者[(24.9±8.1)岁vs.(22.2±6.2)岁,P0.05]。结论:在中国汉族人群中,RTN4R基因多态性与精神分裂症可能不存在关联,但可能影响疾病表现。     

AKT1基因多态性与利培酮治疗精神分裂症8周疗效的关联研究

目的:探讨AKT1基因多态性与利培酮治疗首发、未用药精神分裂症8周后疗效的关联。方法:共入组150例符合美国精神障碍诊断与统计手册第4版(DSM-IV)诊断标准的汉族精神分裂症门诊或住院患者,其中完成利培酮(治疗剂量4~6 mg/d)治疗8周者为128例。采用治疗8周后阳性与阴性症状量表(PANSS)减分率评估药物疗效;采用DNA测序方法,在128例汉族精神分裂症患者中,检测AKT1基因4个单核苷酸多态性(SNP)位点(rs1130214、rs10149779、rs1130233、rs2494732)的基因型,并采用数量性状位点分析方法(QTL)探索AKT1基因多态性与利培酮治疗精神分裂症疗效的关联。结果:AKT1基因rs1130233(GA)及rs2494732多态性(CT)与利培酮治疗精神分裂症8周后PANSS减分率关联显著(P0.05),经多重检验Bonferroni校正后仍有统计学意义。而rs1130214与rs10149779在本样本中与利培酮疗效的关联无统计学意义(P0.05)。结论:本研究提示在中国汉族人群中,AKT1基因多态性可能与利培酮治疗精神分裂症急性期疗效关联,有望对个体化药物疗效预测提供依据。     

蒙古族原发性高血压人群与血管紧张素转换酶ACE I/D基因及血管紧张素原AGT M235T基因多态性的关系

目的研究血管紧张素转换酶（ACE）基因及血管紧张素原（AGT）基因多态性与蒙古族原发性高血压病的关系。方法应用PCR-RFLP技术检测96例原发性高血压患者与正常对照组108名健康受试者血管紧张素转换酶基因第16内含子I／D多态性及血管紧张素原基因第二外显子M235T多态性。结果①蒙古族人群ACE基因I／D位点II、ID、DD基因型频率在高血压组和正常血压组分别为0.44、0．38、0．18和0．42、0．32、0．26，差异无显著性（χ^2=1.693，P=0．192，OR=0．643，95％可信区间0．330-1．254）；②I、D等位基因的频率分别为0．63、0．37和0．58、0．42，差异无显著性（χ^2=0．808，P=0.363，OR=0．834，95％可信区间0．560-1．240）；③AGT M235T位点MM、MT、TT基因型的频率在高血压组和正常血压组分别为0．21、0.73、0．06和0．55、0．34、0．11，两组之间差异无显著性（χ^2=0．495，P=0．482，OR=0．681，95％可信区间0．233-1．993）。④M、T等位基因频率分别为0．58、0．42和0．72、0．28，差异无显著性（χ^2=0．051，P=0．821，OR=1．047，95％可信区间0．702-1．562）；⑤同时分析AGT基因M235T基因型与ACE基因I／D基因型时结果为它们在蒙古族人群患高血压方面无协同作用。各亚组比较高血压组与对照组均无统计学差异，P〉0．05。结论血管紧张素转换酶基因I／D基因型和血管紧张素原基因M235T基因型与蒙古族人群发生原发性高血压无关。     

Comparison of three different forms of HLA-DR4Dw4 proteins

The biochemical behavior and peptide binding properties of a soluble form of the human class II DR4Dw4 molecule (PI-DR4Dw4) were compared to DR4Dw4 molecules containing the transmembrane and cytoplasmic domains that were purified both from B and transfected Chinese hamster ovary cells. Recombinant and B cell-derived DR4Dw4 molecules bound monoclonal anti-DR4Dw4 antibodies with different affinities and varied in their stability in the presence of sodium dodecyl sulfate. The three forms of DR4Dw4 bound peptides with a similar apparent affinity constant, but soluble class II molecules bound up to ten times more peptide than DR4Dw4 containing a transmembrane region. Peptide binding kinetics for soluble DR4Dw4 molecules were 10-20 times faster than for the other two forms of DR4Dw4 molecules. Finally, soluble PI-DR4Dw4/peptide complexes were shown to stimulate T cell proliferation.     

IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy

Immunoglobulin G4-related disease (IgG4-RD) is a recently described inflammatory disease involving multiple organs. Prostate involvement with IgG4-RD is very rare. In this report, we describe a case of IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy. This patient was present with urine retention symptoms. MRI and CT examination revealed the prostatic enlargement and the multiple lymphadenopathy. Serum IgG4 levels were elevated. Prostatic tissue samples resected both this time and less than 1 year earlier showed the same histological type of prostatitis with histopathologic and immunohistochemical findings characteristic of IgG4-RD. The right submandibular lymph nodes excised 2 years earlier were eventually proven to be follicular hyperplasia-type IgG4-related lymphadenopathy. This is the first case of IgG4-RD that began as localized IgG4-related lymphadenopathy and progressed into a systemic disease involving prostate and multiple lymph nodes. This patient showed a good response to steroid therapy. This leads us to advocate a novel pathogenesis of prostatitis, and a novel therapeutic approach against prostatitis. Pathologists and urologists should consider this disease entity in the patients with elevated serum IgG4 levels and the symptoms of prostatic hyperplasia to avoid ineffective medical or unnecessary surgical treatment.     

汉族人群4q亚端粒区等位片段4qA和4qB的结构特征

目的研究中国人4q35亚端粒区等位片段4qA和4qB的结构特征,探讨其与面肩肱型肌营养不良症（facioscapulohumeral muscular dystrophy,FSHD）的内在联系。方法研究对象包括80名无血缘关系的健康成年人。低熔点胶包埋法抽提基因组DNA。同一样品分别进行EcoRⅠ酶切、EcoRⅠ/BlnⅠ双酶切和HindⅢ酶切,脉冲电场电泳分离,p13E-11、4qA和4qB探针Southern印迹,计算4qA/4qB的频率、基因型频率及各型EcoRⅠ片段的长度,SPSS13.0统计软件分析数据。结果4q亚端粒区4qA的频率（46.9%）与4qB（53.1%）基本相等（χ2=1.250,P〉0.05）,4qA/4qB杂合型频率明显高于纯合型频率（P〈0.05）,4qA型和4qB型EcoRⅠ片段长度分别为（115.8±11.9）kb和（98.3±8.6）kb,两者差异有统计学意义（t=23.04,P〈0.001）。8.8%（7/80）的个体检测到易位构型。2名个体出现4qB型短EcoRⅠ片段。结论正常中国人4q亚端粒区4qA和4qB的频率基本相等,杂合型频率明显高于纯合型频率。4qB型D4Z4缺失不致病。4qA和4qB型EcoRⅠ片段具有动态性变化特征。     

Specific amplification of the HLA-DRB4 gene from c-DNA. Complete coding sequence of the HLA alleles DRB4*0103101 and DRB4*01033

We present the complete coding sequence of the HLA alleles DRB4*0103101 and DRB4*01033 derived from the lymphoblastoid cell line G081, established from an individual of Spanish Gypsy ethnic origin. This cell was typed by PCR-SSP and reverse SSO as DRB4*0103101 but further characterization of the DRB4 gene by sequence-based typing (SBT) demonstrated heterozygosity at codon 78 (TAC, TAT). With the aim of confirming this polymorphism, RNA isolated from G081 was subjected to RT-PCR using primers designed to recognize specifically the 5' and 3' UT regions of HLA-DRB4 and the product was cloned and sequenced. Nucleotide sequences derived from seven clones confirmed the heterozygosity of G081, as they corresponded to two open reading frames of 801 nucleotides that matched either DRB4*0103101 or the recently described DRB4*01033, for which a partial sequence, spanning exons 2 and 3, has been reported. The phenotype of G081 (A*01; B*0702, *1302/1303; Cw*0602, *07; DRB1*0403, *0701; DRB4*0103101, *01033; DQB1*0202, *0302; DQA1*0201, *0301) is consistent with a proposed association of DRB4*01033 with DRB1*0403 and DQB1*0302.     

肝素治疗纤溶酶原激活剂抑制物-1基因启动因子区-675 4G/4G基因型基因所致重复流产孕妇的疗效探讨

目的 探讨肝素(heparin)治疗纤溶酶原激活剂抑制物-1基因启动因子区-675 4G/4G基因型基因所致重复流产的疗效.方法 将56例反复性妊娠丢失患者(排除感染、内分泌、子宫附件、免疫等导致流产的其它因素,由纤溶酶原激活剂抑制物-1基因启动因子区-675 4G/4G基因型基因),就诊后一经诊断为妊娠即给分为两组,分别给予肝素治疗或不给予任何干预.观察两组的妊娠结局. 结果肝素治疗24例中,22例足月产(91.66%)、2例早产35.9±1.6w(33～37.6)并产出活婴(11.11%)、活产率100%.比对照组50% (12/24),差异有显著性(P＜0.01).结论 肝素对纤溶酶原激活剂抑制物-1基因启动因子区-675 4G/4G基因型基因所致重复流产孕妇的治疗效果显著.     

Expression of CTLA-4 (CD152) on human medullary CD4+ thymocytes

CTLA-4 (CD152) is a T cell surface receptor with sequence homology to the co-stimulatory molecule CD28. The molecule, which is essential for the inhibitory regulation of the immune response, becomes transiently expressed on mature T cells after stimulation in vitro. In situ, CTLA-4⁺ T cells are enriched in the light zones of the germinal centers in human peripheral lymphoid organs. In this study we have studied expression of CTLA-4 in human thymus in situ. CTLA-4 was expressed on about one third of CD4⁺/CD8^–/CD1^– medullary thymocytes. CTLA-4 was acquired by a subset of immature (CD1⁺) thymocytes and lost from the mature (CD1^–) subpopulation within 48 h of cell culture, suggesting that the expression on medullary thymocytes is transient. The demonstration of CTLA-4 on a substantial subpopulation of mature CD4⁺ thymocytes adds a new dimension to the understanding of this important molecule. When contemplating application of anti-CTLA-4 for therapy its potential influence on T cell maturation has to be taken into account. Received: 5 January 1998     

The influence of CD4 and CXCR4 on maedi-visna virus-induced syncytium formation

CD4 is the principal binding site for human and simian immunodeficiency virus (HIV/SIV) receptor interactions and the a chemokine receptor CXCR4 has been implicated as a primordial lentivirus receptor. This study sought to determine the relevance of CD4 and CXCR4 in virus-receptor interactions for the prototype lentivirus, maedi-visna virus (MVV) of sheep. Neither CD4 nor alpha/beta chemokine receptors represent principal receptors for MVV since human osteosarcoma cells devoid of these molecules were susceptible to productive infection. Interestingly, the presence of either CD4 and/or CXCR4 on indicator cells dramatically enhanced MVV-induced cell fusion (syncytium formation) for three independent virus strains. Syncytium formation results from virus-receptor interactions and can be inhibited by receptor ligands. However, neither SDF-la that binds CXCR4 nor recombinant gp120 (rgp120) that binds CD4 could specifically inhibit the observed enhancement of MVV-induced cell fusion under conditions that significantly reduced HIV-1-induced cell fusion. Our observations suggest that CD4 and CXCR4 may represent optional auxiliary components of an MVV receptor (or receptor complex) that facilitate MVV-mediated membrane fusion events, a feature important for virus entry. This potential accessory role for CXCR4 in MW receptor interactions may reflect the distant relationship between the ovine (MVV) and the human/feline lentiviruses (HIV/FIV).