Candidate genes associated with ageing and life expectancy in the Jerusalem longitudinal study

In an exploratory study, 11 common polymorphisms were examined for contributing to longevity including: apolipoprotein E (apoE), methylenetetrahydrofolate reductase (MTHFR), cathepsin D (CAD), superoxide dismutase 2 (SOD2), angiotensinogen (AGT) and insulin-like growth factor 2 (IGF2), Leiden factor 7, p53 oncogene, dopamine D4 receptor (DRD4) and the serotonin transporter (SERT). Genotype and allele frequencies of these genes were compared in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity to a group of 441 younger subjects (22 years). Nominally significant results provide suggestive evidence in the Ashkenazi group that apoE, MHTFR, SOD2, IGF2 ApaI, and factor VII are risk factors for a single outcome, survival to 75. Overall, the more genetically homogenous Ashkenazi ethnic group showed evidence for association in five genes examined suggesting that future studies in this population would gainfully focus on this ethnic group.     

Veränderungen der Serum-Antiotensinogen-Konzentration bei akuter Hepatitis und Lebercirrhosen

Zusammenfassung Die Angiotensinogen-Konzentration im Serum ist in der akuten und Abheil-Phase der Hepatitis (n=16) auf durchschnittlich 72–81% der Norm herabgesetzt. Bei 19 kompensierten und 10 dekompensierten Lebercirrhosen findet sich eine Substratverminderung auf 50%. Korrelationsstatistisch ist ein Zusammenhang zum Serum-Bilirubin, Albumin und Gesamtprotein sowie zur Transaminase-Aktivität weder für die Hepatitis- noch für die Cirrhose-Gruppe nachweisbar. Ebenso ergibt sich bei Lebercirrhosen keine statistisch gesicherte reziproke Abhängigkeit zwischen Serum-Renin-Aktivität und Angiotensinogen-Spiegel. Auch bei hochgradiger Funktionseinschränkung ist die Leber noch zur Substratsynthese befähigt. Ein totaler Schwund ist selten.     

Glial fibrillary acidic protein (GFAP) immunochemical profile after Junin virus infection of rat cultured astrocytes

After five steps of purification including gel permeation, anti-angiotensin I affinity column chromatography followed by reverse-phase HPLC, a peptide immunoreactive to two different antisera (anti-angiotensin I) was purified to homogeneity from extracts of the leech Theromyzon tessulatum. The first 14 amino acid residues of the purified peptide (DRVYIHPFLLXWG) established by automated Edman degradation, reveal the existence in leeches of an angiotensin I-like molecule close to human angiotensin I. The sequence of the purified peptide presents 78.5% of homology with the N-terminal part of human angiotensin. Moreover, in its sequence, this peptide presents the cleavage sites of vertebrate angiotensin metabolic enzymes, i.e. the renin and the angiotensin-converting enzyme. This finding constitutes the first biochemical characterization of an angiotensin I in Invertebrates. It also reflects the high conservation of angiotensins in the course of evolution, suggesting a fundamental role of this family in fluid homeostasis.     

妊高征患者胎盘组织血管紧张素Ⅱ 1型受体和血管紧张素原的表达

目的　探讨血管紧张素Ⅱ 1型受体 (angiotensinⅡtype 1receptor ,AT1R)和血管紧张素原 (angiotensinogen ,AGT)在妊娠高血压综合征 (妊高征 )患者胎盘组织中表达的变化及其在妊高征发病中的意义。　方法　采用免疫组织化学染色法 (免疫组化 )和逆转录聚合酶链反应法 (RT PCR) ,检测 2 0例中、重度妊高征患者 (妊高征组 )和 15例正常妊娠妇女 (正常组 )的胎盘组织AT1R水平及AT1RmRNA和AGTmRNA的表达。　结果　 ( 1)AT1R主要定位于胎盘绒毛滋养细胞、血管内皮细胞及血管平滑肌细胞。 ( 2 )免疫组化定量灰度分析 ,妊高征组胎盘组织AT1R阳性表达( 112 .4 3± 11.75 )显著强于正常组 ( 170 .4 7± 10 .5 9) (P <0 .0 1)。 ( 3)妊高征组胎盘组织AT1RmRNA的表达水平 ( 0 .96± 0 .2 0 )高于正常组 ( 0 .5 6± 0 .14 ) (P <0 .0 1)。妊高征组胎盘组织AGTmRNA的表达水平 ( 1.0 8± 0 .2 2 )亦显著高于正常组 ( 0 .6 0± 0 .12 ) (P <0 .0 1)。　结论　在妊高征患者胎盘组织中 ,AT1R和AGT表达均有明显增加 ,说明胎盘组织局部肾素 血管紧张素系统与妊高征发病有相关性     

Risk conferred by tagged SNPs of AGT gene in causing susceptibility to essential hypertension

Introduction: AGT gene harbors several variants of which 21 are found to be in high linkage disequilibrium as per Hapmap database. Studies delineating the importance of these tagged SNPs are very limited and lacking from Indian population. In the present study, we evaluated the contribution of four tagged SNPs namely, g.6635G?>?A, g.6506G?>?A, g.12840G?>?A, and g.13828T?>?C at AGT locus along with the analyses of haplotype and epistatic interactions in causing susceptibility to essential hypertension (EHT).

Methods: About 215 hypertensives and 230 normotensives were genotyped for selected tagged SNPs using PCR-RFLP method.

Results: Significant association was obtained for g.6635G?>?A and g.6506G?>?A polymorphisms wherein GG homozygotes for both the markers were at risk for developing the condition. g.13828T?>?C polymorphism specially, female heterozygotes (TC) were found to be at increased risk for EHT. Haplotype GGGC was found to have a significant protective effect (p?=?0.0059). Markers g.6506G?>?A and g.12840G?>?A resulted in the creation of new enhancer sites thereby affecting splicing process.

Conclusion: The present report is the first one in the literature showing general- and gender-specific association of g.6506G?>?A and g.13828T?>?C polymorphisms, respectively, with EHT. However, further studies for replication of present observations are warranted from other populations and other parts of India.     

Measurement Of Angiotensinogen In Human Serum By Fluorescence Polarization Immunoassay

Fluorescence polarization immunoassay (F.P.I.A.) has rarely been used to measure components of the renin system. Using an Abbott TDX polarimeter and fluorescein - labelled angiotensin I as a tracer we measured angiotensin I by F.P.I.A. Combining this procedure with a renin incubation step enabled measurement of angiotensinogen in human serum. Using sera from male patients and from pregnant females, a good correlation between radioimmunoassay (R.I.A.). and F.P.I.A. was found. Two procedures were developed; one involving taking samples from the renin incubation mixture, the other involving measurement of generated angiotensin I at intervals without interrupting the renin incubation procedure. F.P.I.A. is less expensive and somewhat simpler than R.I.A. but, with the instrument used, it     

The Influence of Aging on Angiotensinogen Production By Rat Vascular Smooth Muscle Cells in Vitro

Aortic smooth muscle cells from 3,12 and 24 mo old rats were grown in cell culture. All of the cultures produced angiotensinogen, but cultures from 24 mo old rats produced significantly more (p<0.01). These results suggest that angiotensinogen is synthesized in arterial smooth muscle. Furthermore, when the activity of the plasma renin system decreases with advancing age, increased activity of a local angiotensin system may contribute to the regulation of vascular tone.     

血管紧张素原基因多态性与慢性心力衰竭的相关性研究

目的探讨血管紧张素原基因(AGT)多态性与慢性心力衰竭(CHF)发病的关系。方法应用聚合酶链反应-限制性片段长度多态性技术检测2004年4月至2005年12月珠海市3家医院的111例CHF患者和110名健康对照者的AGT基因M235T多态性并进行统计学比较。结果共检测出3种AGT基因型,分别为MM型、MT型和TT型。CHF患者TT基因型频率高于对照组,在老年病例与对照组间,差异具有统计学意义(P=0.042)。与非TT型者相比,老年TT型者发生CHF的相对风险率为3.367。结论AGT基因M235T多态性与CHF的发生相关,TT基因型可能是该地区老年人群CHF发病的遗传危险因素。     

原发性高血压与血浆肾素活性及血管紧张素原遗传关系研究

目的：分析血浆肾素活性（ＰＲＡ）、血浆血管紧张素原（ＡＯ）浓度与原发性高血压的关系。方法：在一个原发性高血压家系中随机抽取原发性高血压患者３１例（原发性高血压组）、正常血压者２５例（家系对照组），在６个正常对照家系中随机抽取２１例（正常对照组），测定ＰＲＡ、血浆ＡＯ及其它代谢因素。结果：调整年龄、性别、体重指数后原发性高血压家系内无论有无原发性高血压患者，ＰＲＡ均显著低于正常对照组（Ｐ＜００５）；原发性高血压组血浆ＡＯ显著高于正常对照组（Ｐ＜００５），高密度脂蛋白胆固醇显著低于正常对照组（Ｐ＜００５）。结论：具有原发性高血压遗传因素者无论是否患有原发性高血压均有显著的ＰＲＡ、血浆ＡＯ异常和其它代谢紊乱，这些异常可能在超重和原发性高血压发生前即已存在