EFFECT OF A2-ANTIPLASMIN POLYMORPHISM ON CLOTTING MEASURES

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。本研究的目的是检测a2-抗纤溶酶(a2-AP)基因内单核苷酸多态(SNP)的频率。该SNP导致a2-AP长链第6位的单一氨基酸从精氨酸(R)变为色氨酸(W)。我们的目的是确定SNP在普通人群中的频率，并确定这如何影响2-AP水平、蛋白质序列和体外凝血指标。将招募代表普通民众的300名捐赠者。这些捐赠者中的大多数预计将是OUHSC的员工、学生或校园访客，他们将通过克里斯汀森博士在校园内张贴的广告进行招募。参加者将被要求在上午8点至10点到GCRC。并在抽血前禁食至少8小时。在征得知情同意后，将测量和记录身高和体重，然后医生、护士或训练有素的采血员将利用无菌技术，通过静脉穿刺法将20毫升血液抽入ACD抗凝剂中。抽血后，将向参赛者提供零食。将从1毫升的血液中提取DNA。聚合酶链式反应技术将被用来扩增包含该多态的a2-appro部分。通过对聚合酶链式反应产物进行测序，确定基因分型。其余的血液将被离心，收集血浆并冷冻，用于测定a2-AP水平、蛋白质序列、a2-appros裂解酶活性以及用于体外凝血研究。本研究的目的是检测2-抗纤溶酶(2-AP)基因中单核苷酸多态(SNP)的频率。该SNP导致2-AP长链第6位的单一氨基酸从精氨酸(R)变为色氨酸(W)。我们的目的是确定SNP在普通人群中的频率，并确定这如何影响2-AP水平、蛋白质序列和体外凝血指标。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this research project is to examine the frequency of a Single Nucleotide Polymorphism (SNP) within the gene for a2-antiplasmin (a2-AP). This SNP results in a single amino acid change from arginine (R) to tryptophan (W) at position 6 of the long form of a2-AP. Our aim is to determine the frequency of the SNP in the general population, and to determine how this affects a2-AP levels, protein sequence, and in vitro clotting measures. 300 donors representing the general population will be recruited. The majority of these donors is expected to be OUHSC employees, students, or visitors to campus and will be recruited with an advertisement posted on campus by Dr. Christiansen. The participants will be asked to come to the GCRC between 8 and 10 a.m. and be fasting for at least 8 hours before the blood draw. After obtaining informed consent, height and weight will be measured and recorded, then a physician, nurse or trained phlebotomist will utilize sterile technique to draw 20 ml of blood by venipuncture into ACD anticoagulant. Following the blood draw, a snack will be provided to participants. DNA will be isolated from 1 ml of the blood. PCR techniques will be used to amplify the portion of the a2-APpro encompassing the polymorphism. The genotype will be determined by sequencing of the PCR product. The remainder of the blood will be centrifuged and the plasma collected and frozen for determination of a2-AP levels, protein sequence, a2-APpro-cleaving enzyme activity and for in vitro clotting studies. Specific Aims The purpose of this research project is to examine the frequency of a Single Nucleotide Polymorphism (SNP) within the gene for 2-antiplasmin ( 2-AP). This SNP results in a single amino acid change from arginine (R) to tryptophan (W) at position 6 of the long form of 2-AP. Our aim is to determine the frequency of the SNP in the general population, and to determine how this affects a2-AP levels, protein sequence, and in vitro clotting measures.