中国人GFPT2基因单核苷酸多态性与北方汉族人群2型糖尿病发生的相关性

目的 研究新诊断2型糖尿病(T2DM)易感基因谷氨酰胺:果糖-6-磷酸酶酰胺转移酶(GFPT)单核苷酸多态性与中国北方汉族人群T2DM的关系.方法 实验分T2DM组和正常对照组,用酚/氯仿法提取其外周血DNA行PCR扩增,分离纯化目的条带后直接测序.结果 GFPT2基因的第14外显子中SNP7位点等位基因为C/T,携带等位基因T的个体T2DM发病率较携带等位基因CC的个体显著升高,两组该等位基因T频率有统计学差异(P<0.01).结论 GFPT2等位基因可能是中国北方汉族人群T2DM主要易感基因位点之一.     

MGEA5基因单核苷酸多态性与中国北方汉族人群2型糖尿病的相关性研究

目的研究MGEA5基因单核苷酸多态性与中国北方汉族人群2型糖尿病（T2DM）的相关性。方法实验分糖尿病组（DM）和正常对照组（NC），用酚／氯仿法提取外周血DNA行PCR扩增，扩增产物用1．5％琼脂糖电泳，分离纯化目的条带后直接测序。结果MGEA5基因的内含子10中，SNP5—14位点等位基因为A／T，携带等位基因T的个体DM发病率比携带等位基因AA的个体显著增加，该等位基因T频率在两缉间的差异有统计学意义（P〈0．01）。结论MGEA5—14等位基因可能是中国北方汉族T2DM的主要易感基因位点。     

内脏脂肪素基因多态性与宁夏回、汉族2型糖尿病患者的相关性研究

目的 探讨内脏脂肪素基因启动子区-1535 C/T基因多态性与宁夏回、汉族T2DM的相关性. 方法 用PCR-RFLP方法检测210例宁夏回、汉族T2DM患者(T2DM组)及207名健康对照者(NC组)内脏脂肪素启动子区-1535 C/T位点多态性. 结果 两组间及两组内回、汉族内脏脂肪素基因启动子区-1535 C/T基因多态性位点CC、CT、TT3种基因型和等位基因频率差异均无统计学意义(P＞0.05).回族T2DM组TT基因型HDL-C低于CT、CC基因型(P=0.007),汉族T2DM组TT基因型TG较CC、CT基因型高(P=0.026). 结论 内脏脂肪素基因启动子区-1535 C/T位点存在多态性,两组间回、汉族差异无统计学意义;TT基因型可能与T2DM患者血脂异常有关.     

乙酰辅酶A羧化酶β基因多态性与2型糖尿病易感性关系的初步研究

目的 研究上海地区汉族人群中乙酰辅酶A羧化酶B（ACC-β）的2个单核苷酸多态性（SNP）位点与2型糖尿病（T2DM）易感性的关系。方法 采用等位基因专一性实时PCR的方法对上海地区438例T2DM患者及328名正常对照者（NC）ACC-β基因的2个SNP位点进行分析。结果 （1）ACC-β基因16号内含子区存在SNP位点116／73C＞T，T2DM组和NC组两组间基因型频率比较，差异有统计学意义（P=0．031）。且CC型＋CT型与TT型的分组比较在两组间的差异也有统计学意义（P=0．027）。（2）ACC-B基因16号内含子区还存在另-SNP位点：116／288A〉G，T2DM组G等位基因的频率高于NC组，但无统计学意义。结论 在上海地区的汉族人群中，ACC-β基因可能是T2DM的易感基因之一，其16号内含子区的116／73C＞T多态性（rs2268393）可能与T2DM的发病相关。     

mTOR基因多态性与2型糖尿病及其临床特点的相关性研究

目的 探讨我国汉族人群中mTOR基因的单核苷酸(SNP)位点(rs2295080)多态性与T2DM及其相关临床指标变化的相关性. 方法 采用病例对照研究,分别选取T2DM患者(T2DM组)213例和同期体检健康者(NC组)248名.采用聚合酶链反应-限制性片断长度多态性分析法(PCR-RFLP)测定mTOR基因SNP位点(rs2295080)多态性分布,并进行统计学分析. 结果 T2DM组SNP位点(rs2295080)基因型频率与NC组比较,差异有统计学意义(P=0.046),等位基因T频率高于NC组(OR=1.493,95％CI:1.077～2.069,P=0.016).T2DM组该位点多态性与FPG、HbA1 c、HDL-C、LDL-C及TC无相关性(P＞0.05),与TG相关(P＜0.05). 结论 mTOR基因SNP位点多态性与T2DM发病相关,且在T2DM患者中,SNP位点rs2295080多态性与TG水平相关.     

KATP通道基因多态性与2型糖尿病及磺脲类药物疗效的相关性

目的 探讨ATP敏感性钾(KATP)通道基因ABCC8、KCNJ11单核苷酸多态性(SNPs)与山东汉族2型糖尿病(T2DM)遗传易感性的关系,并观察与磺脲类药物疗效的相关性.方法 选取山东济宁地区的正常对照组(NC组)100例,T2DM组200例,并将T2DM组分为磺脲类继发失效(SFS)组86例,有效组114例,运用ABI SNaPshot技术(ABI Biosystem,USA)对ABCC8、KCNJ11基因上2个典型的SNPs进行基因分型.结果 (1) ABCC8基因rs1799854在NC组和T2DM组等位基因频率及基因型构成差异有统计学意义(P＜0.05),T2DM组危险等位基因t显著高于NC组(P＜0.05);KCNJ11基因rs5219在NC组和T2DM组等位基因频率及基因型构成差异无统计学意义(P＞0.05).(2)在200例服用磺脲类降糖药物的T2DM患者中,仅发现ABCC8基因rs1799854在磺脲类继发失效组及有效组等位基因频率及基因型构成差异有统计学意义(P＜0.05),且“t”等位基因的频率在失效组人群中显著增高(P＜0.05).结论 ABCC8基因rs1799854 t/t多态性可能显著增加山东汉族人群T2DM遗传易感性,并且可能与SFS相关;KCNJ11基因rs5219可能与山东地区T2DM遗传易感性及磺脲类药物疗效无关.     

褪黑色素受体1B基因多态性与妊娠期糖尿病的相关性研究

目的探讨我国褪黑色素受体1B(MTNR1B)基因SNP位点rs10830963和rs1387153的多态性与妊娠期糖尿病(GDM)遗传易感性的关系。方法采用病例对照研究,分别选取GDM患者(GDM组)184例和对照(NC)组235名,利用PCR-RFLP的方法测定2个SNP位点多态性分布,并进行统计学分析。结果 GDM组FPG高于NC组(P=0.039),但孕前BMI比较差异无统计学意义。SNP位点rs10830963基因型(GG,GC,CC)频率、等位基因频率与NC组比较,差异均无统计学意义(P=0.637,P=0.422)。而SNP位点rs1387153基因型(TT,CT,CC)与NC组比较,差异有统计学意义(P=0.012),且风险基因型TT的频率高于NC组(TTvs TC+CC,P=0.01)。GDM组T等位基因高于NC组(OR:1.517,95%CI:1.147~2.006,P=0.003),且该SNP位点的TT基因型的GDM患者FPG高于其他两个基因型的患者。结论 MTNR1B基因SNP位点rs10830963与GDM无相关性,而SNP位点rs1387153与GDM的易感性相关。     

脂联素受体1基因多态性与2型糖尿病相关性研究

目的研究西安地区汉族人群中脂联素受体1（AdipoR1）的两个单核苷酸多态性（SNP）位点与2型糖尿病（T2DM）的关系。方法采用突变特异性扩增系统（ARMS）结合测序方法对西安地区100例T2DM患者（T2DM组）及84名正常对照者（NC组）AdipoRl基因的两个SNP位点进行分析。结果（1）AdipoR1基因SNP-106A／G、SNP 5843A／G在DM组与NC组间基因型频率及等位基因频率差异无统计学意义。（2）AdipoR1基因5843G／G型T2DM患者的诊断年龄明显早于A／A型＋A／G型。结论在西安地区的汉族人群中，AdipoR1基因-106A／G、5843A／G的单个核苷酸多态性可能与T2DM的发病无关。携带5843G／G基因型的T2DM患者发病年龄较早。     

血管内皮生长因子基因SNPrs3025039多态性与2型糖尿病相关性的研究

目的探讨T2DM患者血管内皮生长因子(VEGF)基因SNPrs3025039多态性。方法运用PCR-RFLP检测170例T2DM患者(T2DM组)和100名健康体检者(NC组)的VEGF基因SNPrs3025039多态性。结果 (1)两组的基因型和等位基因频率差异无统计学意义(P>0.05),但糖尿病慢性肾脏疾病(CKD)组CT、TT基因型频率和T等位基因频率高于糖尿病非CKD(NCKD)组(P<0.05);CC基因型和C等位基因频率低于NCKD组(P<0.05);(2)T2DM组BMI、SBP、DBP、HbA1c、FPG、2hPG、TG水平高于NC组(P<0.01),HDL-C水平较NC组降低(P<0.01)。结合FPG、TG、TC、LDL-C及HDL-C进行多重Logistic回归分析显示,CT和TT基因型与CKD的发生呈正相关(OR=2.75,P<0.05)。结论 T2DM患者VEGF基因SNPrs3025039多态性与正常人群比较差异无统计学意义,但CT、TT基因型与CKD的发病风险有关。     

CYP2J2基因和EPHX2基因多态性与缺血性脑卒中的遗传易感性

目的 研究我国汉族人群细胞色素P450表氧化酶2J2(CYP2J2),可溶性环氧化物水解酶2(EPHX2)基因多态性与缺血性脑卒中的关系.方法 选择200例缺血性脑卒中患者和350例健康人群,采用PCR-RFLP技术分析两个基因CYP2J2 G-50T,EPHX2 G860A多态性的基因型.结果 仅EPHX2 860A等位基因频率在缺血性脑卒中组与对照组比较有显著性差异.多元Logistic回归分析表明,携带EPHX2 860A等位基因的人群患缺血性脑卒中相对风险率下降50%(OR=0.5).当个体同时携带CYP2J2-50GG和EPHX2 860A (A 示A等位基因)联合基因型时,其患缺血性脑卒中相对风险率下降53.9%(OR=0.461).结论 虽然EPHX2 860A等位基因与缺血性脑卒中有相关性并且为缺血性脑卒中一个独立的保护因子,但联合基因型CYP2J2-50GG/EPHX2 860A 的协同作用对缺血性脑卒中有更强的保护作用.     

CYP2J2基因和EPHX2基因多态性与肺癌易感性研究

目的探讨CYP2J2基因启动子区G-50T多态性和EPHX2基因G860A多态性与肺癌发生的关系。方法经病理检查确诊为肺癌患者150例（肺癌组）,300名本院健康体检者作为对照组,检测其CYP2J2基因启动子区G-50T多态性和EPHX2基因G860A多态性,并进行统计学分析。结果肺癌组和对照组比较,CYP2J2启动子区G-50T多态性差异无统计学意义,而肺癌组患者EPHX2 860G等位基因频率显著高于对照组人群（96％比78．3％,P〈0．01）,多元回归分析方法显示,肺癌的发生与EPHX2 G860A多态性显著相关（校正OR值=0．164,95％CI 0．079～0．342,P〈0．001）。结论EPHX2 G860A多态件与肺痛密切相关．可作为肺癌高毹患者的预涮指标．     

The effects of changes of maternal PaO2 and PaCO2 on the fetal PaO2 and PaCO2--in vivo study

Umbilical PaO2 and PaCO2 were continuously monitored in vivo in acute fetal lamb preparations with a semipermeable membrane connected to a mass spectrometer. The response time of this system (0 to 90% of final value) was 36 sec. In seven pregnant sheep (128--135 days gestation) the maternal inspired mixture was abruptly changed and the following changes in fetal PaO2 and PaCO2 were observed: (1) 100% O2 to room air: PaO2 decreased from 21.5 +/- 0.8 (mean +/- SEM) to 14 +/- 1.1 mm Hg at a rate of 1.63 +/- 0.33 mm Hg/min. Following return to 100% O2 the PaO2 returned to 21 +/- 1.1 mm Hg at a rate of 2.44 +/- 0.4 mm Hg/min. (2) 100% O2 to 12% O2/10% CO2: after 6 min the PaO2 fell from 19.3 +/- 1.3 to 6.3 +/- 0.3 mm Hg at a rate of 4.65 mm Hg/min and the PaCO2 rose from 37 +/- 8 to 70 +/-5 mm Hg. At 100% O2 the PaO2 returned to 19 +/- 1.0 mm Hg at a rate of 11.76 +/- 0.086 mm Hg, the PaCO2 to 39 +/- 7 mm Hg. (3) 100% O2 to 90% O2/10% CO2. The PaO2 and PaCO2 increased by 4.7 and 22 mm Hg, respectively. The changes of fetal PaO2 and PaCO2 occurred after 1 minute of changing in maternal inspired mixture except in the transition from 12% O2/10% CO2 to 100% O2 (34 +/- 12 sec). Following the reinstitution of 100% the fetal PaO2 and PaCO2 returned to their previous values within 4 and 16 min, respectively.     

Effects of neuraminidase on O2 consumption and release of O2 and H2O2 from phagocytosing human polymorphonuclear leukocytes

Neuraminidase type X (NMD-type-X, Sigma Chemical Co., St. Louis, Mo.), which is obtained from a further purification of neuraminidase type V (NMD-type-V, Sigma), markedly enhanced the release of O2- and H2O2 from phagocytosing human polymorphonuclear leukocytes (PMN). In contrast, O2 consumption by NMD-type-X-treated PMN was identical to that of untreated PMN. Morphological observations suggested that the enhancement of O2- and H2O2 release was caused by excessive release of the oxygen metabolites into the extracellular medium from incompletely formed phagocytic vacuoles as was observed with cytochalasin-B-treated cells. Our observations are in contrast to the previous reports of Tsan et al. that showed complete inhibition of both O2- and H2O2 release from phagocytosing PMN by the treatment with NMD-type-V.     

Different RBC aggregating properties of the Aalpha2Bbeta2gammaA2 and Aalpha2Bbeta2gammaAgamma' subpopulations of human fibrinogen

Human fibrinogen (TF) has been separated into two fractions: F1 - homodimers with respect to the gamma chain, and F2 - heterodimers composed of gammaA and gamma' polypeptides. Their rouleaux-inducing properties were as follows: (1) both, at the same concentration of 0.8%, were less effective than TF; (2) F1 produced larger rouleaux even under static conditions of a hemocytometer where F2 was silent; (3) F2 induced the process when a suspension was gently sheared between microscopic slides. Since the synthetic peptide gamma'(414-427) inhibited the rouleau formation in a mixture with F2, the C-terminal amino acids of the gamma' polypeptide probably bind the molecule to the cell. The inhibition was feebly visible in the native ratio of F1/F2, implicating a compensatory effect of F1.     

Expirograms of O2, CO2 and intravenously infused C2H2 and Freon-22 during panting in dogs

To study pulmonary gas transport in panting, expirograms of several inert and respiratory gases were simultaneously measured in panting dogs. The experiments were performed on 5 conscious dogs (mean body weight 34.4 kg) provided with a chronic tracheostomy. Panting at a mean frequency of 312/min (5.2 Hz) was induced by elevated room temperature (mean 28.1 degrees C). Isotonic saline equilibrated with 50% acetylene and 50% Freon-22 was infused intravenously at a constant rate (4 ml/min). Fractional concentrations in the tracheostomy tube were measured by a respiratory mass spectrometer, using a special sampling system designed for quasi-continuous analysis of rapidly changing gas concentrations. Air flow was monitored by an ultrasonic transit-time flowmeter. A tracing of expired gas concentrations versus expired volume showed no alveolar plateau, displaying a steep increase of Freon-22, acetylene and CO2 (decrease of O2) up to the onset of inspiration. The small but statistically highly significant differences between the expirograms of CO2 and O2, and of Freon-22 and acetylene, could be qualitatively explained by ventilation-perfusion inequalities with sequential emptying, by Taylor dispersion and by reversible solution in airway mucosa in the course of the respiratory cycle.