E-钙粘蛋白基因启动子区域单核苷酸基因多态性(-160A/C)和大肠癌遗传易感性的联系

目的:探讨E-钙粘蛋白基因(CDH1)启动子区域-160A/C单核苷酸基因多态性(single nucleotide polymorphism,SNP)和中国地区散发大肠癌(colorectal cancer,CRC)人群遗传易感性的联系。方法:以中国地区大肠癌病人群为研究基础,同时建立无肿瘤家族史以及其它遗传性疾病史的正常对照组,进行病例对照研究,采用聚合酶链反应-限制性片段长度多态性技术(polymerasechain reaction-restriction fragment length polymorphism,PCR-RFLP)行目的基因的多态性测定,同时行正常结肠组织和大肠癌组织的E-钙粘蛋白的免疫组化测定。结果:正常对照组和大肠癌组的目的基因型分布频率并无统计学差异(x2检验,P=0.602),同时A基因型和C基因型在正常结肠组织和大肠癌组织中E-钙粘蛋白的表达量也并无差异(t检验,P>0.05)。结论:CDH1启动子区域-160A/C单核苷酸基因多态性中并不单独增加大肠癌的发病风险。     

亚甲基四氢叶酸还原酶基因C677T、G1793A 单核苷酸多态性 与散发性乳腺癌易感性的关系

目的:研究亚甲基四氢叶酸还原酶(MTHFR)基因C677T、G1793A位点单核苷酸多态性与散发性乳腺癌易感性关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,对200例乳腺癌患者及200例正常对照者MTHFR基因C677T、G1793A位点单核苷酸多态性进行分析,logistic回归分析不同基因型与乳腺癌风险的关系。结果:乳腺癌组MTHFR 677TT基因型频率为25.00%显著高于正常对照组的10.50%(X2=14.401,P=0.001),CT基因型频率为44.50%低于正常对照组的54.50%,CC基因型频率在乳腺癌组和正常对照组中无差别;MTHFR 1793GA基因型频率为18.50%显著高于正常对照者的8.50%(X2=8.563,P=0.003)。乳腺癌患者MTHFR 677T和1793A等位基因频率分别为47.25%、9.25%,显著高于对照组中的37.75%、4.25%。MTHFR 677TT基因型携带者罹患乳腺癌的风险是677CC基因型携带者的2.732倍(95%CI=1.418～5.051,P=0.001),MTHFR1793GA基因型携带者罹患乳腺癌的风险是1793GG基因型携带者的2.444倍(95%CI=1.325～4.505,P=0.003)。另外,乳腺癌组中MTHFR C677T基因多态性与肿瘤大小相关(x2=7.431,P=0.024,MTHFR G1793A基因多态性与淋巴结转移情况(x2=8.939,P=0.011)、癌组织学分级(x2=9.983,P=0.007)相关。结论:MTHFR C677T、G1793A基因多态性与散发性乳腺癌的易感性相关。     

北方汉族人群白细胞介素-6基因-572C/G单核苷酸多态性与冠心病的相关性研究

目的:探讨中国北方汉族人群中白细胞介素-6(IL-6)基因启动子区-572C/G单核苷酸多态性与冠心病的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,检测434例冠心病(冠心病组)患者和417名非冠心病人(对照组)的IL-6基因型,探讨-572C/G单核苷酸多态与冠心病的关系。结果:IL-6基因-572C/G多态位点的CC、CG和GG基因型在冠心病组中分别为59.68%、37.09%、3.23%,等位基因频率C和G分别为78.23%、21.77%;在健康成年者中基因型分别为67.87%、30.22%、1.92%,等位基因频率C和G分别为82.97%、17.03%。IL-6基因-572C/G位点多态性在两组人群中的分布差异存在显著性(P<0.05);经Logsitic回归校正性别、年龄、体重指数、高血压病、糖尿病、高胆固醇血症及吸烟等冠心病易患因素后,IL-6基因-572C/G单核苷酸多态是冠心病发病的独立的危险因素(P<0.05);等位基因频率的相对风险分析发现,G等位基因携带者患冠心病的风险是C等位基因的1.356倍〔OR=1.356,95%CI=1.0648～1.7279〕。...     

亚甲基四氢叶酸还原酶基因C677T、G1793A单核苷酸多态性与散发性乳腺癌易感性的关系

目的：研究亚甲基四氢叶酸还原酶（MTHFR）基因C677T、G1793A位点单核苷酸多态性与散发性乳腺癌易感性关系。方法：采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法,对200例乳腺癌患者及200例正常对照者MTHFR基因C677T、G1793A位点单核苷酸多态性进行分析,logistic回归分析不同基因型与乳腺癌风险的关系。结果：乳腺癌组MTHFR 677TT基因型频率为25.00%显著高于正常对照组的10.50%（X2=14.401,P=0.001）,CT基因型频率为44.50%低于正常对照组的54.50%,CC基因型频率在乳腺癌组和正常对照组中无差别;MTHFR 1793GA基因型频率为18.50%显著高于正常对照者的8.50%（X2=8.563,P=0.003）。乳腺癌患者MTHFR 677T和1793A等位基因频率分别为47.25%、9.25%,显著高于对照组中的37.75%、4.25%。MTHFR 677TT基因型携带者罹患乳腺癌的风险是677CC基因型携带者的2.732倍（95%CI=1.418～5.051,P=0.001）,MTHFR1793GA基因型携带者罹患乳腺癌的风险是1793GG基因型携带者的2.444倍（95%CI=1.325～4.505,P=0.003）。另外,乳腺癌组中MTHFR C677T基因多态性与肿瘤大小相关（x2=7.431,P=0.024,MTHFR G1793A基因多态性与淋巴结转移情况（x2=8.939,P=0.011）、癌组织学分级（x2=9.983,P=0.007）相关。结论：MTHFR C677T、G1793A基因多态性与散发性乳腺癌的易感性相关。     

白介素10和白介素17基因启动子区多态性位点与儿童哮喘 的相关性研究

目的:探讨IL-10基因启动子区-627A/C和IL-17基因启动子-152A/G位点多态性与儿童哮喘发生的相关性。方法:采用聚合酶链反应-限制性片段长度多态性分析(PCR-PFLP)方法检测186名哮喘儿童、198名健康儿童各个多态性位点的基因型,采用SPSS13.0进行统计学分析。结果:IL-17基因-152A/G位点的基因型及等位基因频率分布在哮喘组与正常对照组均存在显著性差异(p<0.05),哮喘组-152A/G位点等位基因A频率显著高于正常对照组(x2=6.077,p=0.014,OR=1.430,95%CI=1.076-1.902)。结论:IL-17基因-152A/G位点可能与儿童哮喘的发病存在关系,其中A等位基因可能是易感基因,携带A的个体可能更易患有哮喘。     

β_2-AR基因5’-调控区-654位与-1429位单核苷酸多态性与新疆哈萨克族原发性高血压关系的研究

目的:检测β2-肾上腺素能受体(β2-AR)基因5’-调控区部分序列单核苷酸多态性(SNPs),并探讨这些SNPs与新疆哈萨克族原发性高血压的关系。方法:应用MALDI-TOFMS方法测定β2-AR基因5’-调控区-654位与-1429位单核苷酸多态性确定SNP类型,并进行基因分型。结果:β2-AR基因5’-调控区-654位与-1429位单核苷酸多态性分别为-654位G→A、-1429位T→A碱基变异。2种SNPs基因型频率在正常人群分布符合Hardy-Weinberg平衡。其中-654位SNPs基因型GG、GA、AA频率在正常血压和高血压人群间的分布没有显著性差异(x2=1.26,df=2,P>0.05),位于-1429bp处SNPs基因型在2组人群中分布差异无显著性(x2=1.85,df=2,P>0.05)。结论:β2-AR基因-654位与-1429位SNPs可能仅为基因多态性标志。     

MTHFR基因多态性与中国北方人群脑膜瘤发病的相关性分析

目的:探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与中国北方人群脑膜瘤发病的相关性。方法:选择2012年1月-2013年12月在黑龙江省哈尔滨医科大学附属第二医院的第一、三病房接受手术治疗的脑膜瘤患者317例(实验组)及320例非脑膜瘤患者(对照组)为研究对象,利用聚合酶链反应限制性多态性片段长度(PCR-RFLP)检测和比较两组MTHFR两个单核苷酸多态性位点(C677T、A1298C)各种基因型(CC、CT、TT)的分布情况及等位基因的频率。结果:两组MTHFR的C677T中CC基因型的频率和TT基因型的频率比较有显著性差异(CC:OR=2.012,95%CI=1.460-2.772;TT:OR=0.399,95%CI=0.254-0.628,P0.05),实验组MTHFR的(0.450)C677T中的T等位基因频率明显高于对照组(0.320)(OR=0.529,95%CI=0.420-0.666,P0.05)。两组A1298C的等位基因分布比较没有统计学差别(P0.05)。结论:MTHFR基因的C677T中TT等位基因提示潜在的易患脑膜瘤的风险,而CC等位基因会降低中国北方人群患脑膜瘤的风险。     

天津地区人群hMLH1和hMSH2基因多态性与散发性结直肠癌易感性的关系

为探讨错配修复基因hMLH1和hMSH2单核苷酸多态性(Single nucleotide polymorphism,SNP)与散发性结直肠癌(Sporadic colorectal caner,SCRC)发病易感性之间的关系,文章采用聚合酶链式反应-变性高效液相色谱方法和序列分析技术,检测了天津地区600例SCRC患者和600例健康对照个体hMLH1394G/C、hMSH2943-1G/A、hMSH21917T/G和hMSH22783C/A的基因型频率分布。结果显示:SCRC患者组hMSH22783C/A3种基因型C/C、C/A、A/A频率(90%、9%、1%)与对照组(95%、4.8%、0.2%)相比差异具有统计学意义(χ2=11.91,P0.01)。与hMSH22783C/C基因型相比,C/A和A/A基因型能增加SCRC发病风险(OR值分别为1.77和11.94,95%CI分别为1.03～3.03和1.38～103.2)。多态性位点联合分析显示,SCRC组与对照组单倍型分布差异有统计学意义(χ2=38.38,P0.01);与394G/943-1G/2783C单倍型相比,394G/943-1G/2783A单倍型显著增加SCRC的发病风险(OR=2.18,95%CI:1.40～3.40)。结果提示hMSH22783C/A多态性可能成为预测SCRC发病风险的独立因素,394G/943-1G/2783A单倍型可能增加SCRC的发病风险。     

人染色体8p11(CHRNB3-CHRNA6)区域基因多态性与中国汉族人群肺癌易感性的相关性

为探讨人染色体8p11(CHRNB3-CHRNA6)区域基因多态性与中国汉族人群肺癌遗传易感性之间的关系,文章采用病例-对照研究,对784例肺癌患者和782例性别、年龄、籍贯频数与之相匹配的健康对照中该区域6个标签SNP位点进行基因分型,并统计分析其基因型频率分布与肺癌易感性的关系,以及吸烟在其中的影响。结果发现rs16891561位点TT基因型在60岁以上人群(校正OR=0.42,95%CI=0.20-0.88;P=0.022)、女性人群(校正OR=0.34,95%CI=0.13-0.87;P=0.025)、非吸烟人群中(校正OR=0.32,95%CI=0.13-0.79;P=0.013)对肺癌发生具有保护效应;rs4236926位点TT基因型在60岁以上人群(校正OR=0.48,95%CI=0.23-0.99;P=0.048)、非吸烟人群(校正OR=0.32,95%CI=0.13-0.80;P=0.014)中对肺癌发生具有保护效应,这两种保护效应主要是与腺癌相关。对这两个位点进行累积效应分析发现,含有3~4个变异等位基因型的非吸烟者罹患肺癌的风险显著降低(校正OR=0.29,95%CI=0.11-0.71;P=0.007),并且,含有3~4个变异等位基因型的个体累计吸烟量("包-年"平均数=13.2)与其他个体相比显著降低。由此可见人染色体8p11(CHRNB3-CHRNA6)区域基因多态性与中国汉族人群肺癌易感性和吸烟行为相关。     

BRCA1 基因启动子区SNPs 与散发性乳腺癌易感性的相关研究

目的:探讨BRCA1基因启动子区rs11655505、rs73625095位点单核苷酸多态性与散发性乳腺癌易感性的关系。方法:采用ASA-PCR方法对200例乳腺癌患者(均经病理确诊)及200例正常女性BRCA1基因启动子区rs11655505(A/G)、rs73625095(A/G)位点单核苷酸多态性(SNP)进行分析,并将其PCR产物进行测序。结果:乳腺癌患者BRCA1基因启动子区rs11655505位点的A/G基因型频率为75%,显著高于正常人的40%;A/A基因型频率为7%,G/G基因型频率为18%,分别低于正常人的30%、30%。此位点的A或G等位基因在乳腺癌病例组及对照组中均无差别(x2=2.427,P=0.119);rs73625095位点的A/G基因型频率为68%,显著高于正常人的15%;G/G基因型频率为32%,低于正常人的84%;乳腺癌病例组中BRCA1基因启动子区rs11655505、rs73625095位点的A/G基因型与淋巴结转移与否相比,差别均有统计学意义(x2=7.321,P=0.026、x2=4.782,P=0.029)。结论:BRCA1基因rs11655505位点、rs736...     

Changes in lactate dehydrogenase activity in chicken tissues in hyperthyreosis in ontogenesis

The lactate dehydrogenase activity in reactions of lactate oxidation and synthesis was studied in subfractions of the chicken brain, heart and liver at the embryonal, early postembryonal and adult stages of development after thyroxine administration. It has been shown that during embryogenesis thyroxine predominantly enhanced the rate of lactate oxidation in the mitochondrial tissues. A marked increase in the lactate synthesis was found in cytoplasm of the adult chicken tissues. Specificity of enzyme activity alterations was detected in the chicken brain during ontogenesis after thyroxine administration.     

Scurvy in capybaras bred in captivity in Argentine

In order to determine if the absence of vitamin C in the diet of capybaras (Hydrochoerus hydrochaeris) causes scurvy, a group of seven young individuals were fed food pellets without ascorbic acid, while another group of eight individuals received the same food with 1 g of ascorbic acid per animal per day. Animals in the first group developed signs of scurvy-like gingivitis, breaking of the incisors and death of one animal. Clinical signs appeared between 25 and 104 days from the beginning of the trial in all individuals. Growth rates of individuals deprived of vitamin C was considerably less than those observed in the control group. Deficiency of ascorbic acid had a severe effect on reproduction of another population of captive capybaras. We found that the decrease in ascorbic acid content in the diet affected pregnancy, especially during the first stages. The results obtained suggest that it is necessary to supply a suitable quantity of vitamin C in the diet of this species in captivity.     

Role for dopamine in malonate-induced damage in vivo in striatum and in vitro in mesencephalic cultures

Defects in mitochondrial energy metabolism have been implicated in the pathology of several neurodegenerative disorders. In addition, the reactive metabolites generated from the metabolism and oxidation of the neurotransmitter dopamine (DA) are thought to contribute to the damage to neurons of the basal ganglia. We have previously demonstrated that infusions of the metabolic inhibitor malonate into the striata of mice or rats produce degeneration of DA nerve terminals. In the present studies, we demonstrate that an intrastriatal infusion of malonate induces a substantial increase in DA efflux in awake, behaving mice as measured by in vivo microdialysis. Furthermore, pretreatment of mice with tetrabenazine (TBZ) or the TBZ analogue Ro 4-1284 (Ro-4), compounds that reversibly inhibit the vesicular storage of DA, attenuates the malonate-induced DA efflux as well as the damage to DA nerve terminals. Consistent with these findings, the damage to both DA and GABA neurons in mesencephalic cultures by malonate exposure was attenuated by pretreatment with TBZ or Ro-4. Treatment with these compounds did not affect the formation of free radicals or the inhibition of oxidative phosphorylation resulting from malonate exposure alone. Our data suggest that DA plays an important role in the neurotoxicity produced by malonate. These findings provide direct evidence that inhibition of succinate dehydrogenase causes an increase in extracellular DA levels and indicate that bioenergetic defects may contribute to the pathogenesis of chronic neurodegenerative diseases through a mechanism involving DA.     

SSTR5 ablation in islet results in alterations in glucose homeostasis in mice

Somatostatin (SST) peptide is a potent inhibitor of insulin secretion and its effect is mediated via somatostatin receptor 5 (SSTR5) in the endocrine pancreas. To investigate the consequences of gene ablation of SSTR5 in the mouse pancreas, we have generated a mouse model in which the SSTR5 gene was specifically knocked down in the pancreatic beta cells (betaSSTR5Kd) using the Cre-lox system. Immunohistochemistry analysis showed that SSTR5 gene expression was absent in beta cells at three months of age. At the time of gene ablation, betaSSTR5Kd mice demonstrated glucose intolerance with lack of insulin response and significantly reduced serum insulin levels. Insulin tolerance test demonstrated a significant increase of insulin clearance in vivo at the same age. In vitro studies demonstrated an absence of response to SST-28 stimulation in the betaSSTR5Kd mouse islet, which was associated with a significantly reduced SST expression level in betaSSTR5Kd mice pancreata. In addition, betaSSTR5Kd mice had significantly reduced serum glucose levels and increased serum insulin levels at 12 months of age. Glucose tolerance test at an older age also indicated a persistently higher insulin level in betaSSTR5Kd mice. Further studies of betaSSTR5Kd mice had revealed elevated serum C-peptide levels at both 3 and 12 months of age, suggesting that these mice are capable of producing and releasing insulin to the periphery. These results support the hypothesis that SSTR5 plays a pivotal role in the regulation of insulin secretion in the mouse pancreas.     

2016年中国植物科学若干领域重要研究进展

2016年中国植物科学持续稳步发展, 表现在中国植物科学家在国际主流高影响力学术期刊发表文章的数量稳中有升, 中国植物科学领域的期刊逆风出行, 进入研究性期刊世界前三甲行列。中国科学家在植物学诸多领域取得了丰硕的成果。水稻(Oryza sativa)产量性状杂种优势的分子遗传机制解析入选2016年中国科学十大进展; 植物受精过程中雌雄配子体信号识别机制的研究和独脚金内酯的受体感知机制入选2016年生命科学十大进展。我国植物科学, 特别是以水稻为代表的作物研究在国际学术界已占有一席之地。例如, 在水稻组学(如基因组和转录组等)资源和技术平台的建立、重测序的开发及功能基因的克隆和调控网络的解析方面取得了系列重要成果(如揭示了独脚金内酯信号转导的“去抑制化激活”机制、从分子水平上阐释了水稻籼粳杂种不育和广亲和性基因S5的作用机理及发现了控制水稻耐冷的基因组位点), 已经引领世界水稻乃至作物科学研究。该文对2016年中国本土植物科学若干领域取得的重要研究进展进行了概括性评述, 旨在全面追踪当前中国植物科学领域的发展前沿和研究热点, 与读者共享我国科学家所取得的杰出成就。