EFFECT OF A2-ANTIPLASMIN POLYMORPHISM ON CLOTTING MEASURES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究项目的目的是检测a2-抗纤溶酶（a2-AP）基因内的单核苷酸多态性（SNP）的频率。该SNP导致a2-AP长链第6位的一个氨基酸从精氨酸(R)变为色氨酸(W)。我们的目的是确定SNP在一般人群中的频率，并确定其如何影响a2-AP水平、蛋白质序列和体外凝血措施。将招募代表一般民众的300名捐助者。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，并将通过Christiansen博士在校园内发布的广告进行招募。参与者将被要求在上午8点至10点之间来到GCRC，并在抽血前禁食至少8小时。在获得知情同意后，测量身高和体重并记录下来，然后由医生、护士或经过培训的采血师利用无菌技术静脉穿刺取20毫升血液加入ACD抗凝剂。抽血后，将为参与者提供点心。将从1毫升血液中分离DNA。PCR技术将用于扩增a2-APpro包含多态性的部分。基因型将通过PCR产物的测序来确定。剩余的血液将被离心，收集血浆并冷冻，用于测定a2-AP水平、蛋白质序列、a2-AP切割酶活性和体外凝血研究。本研究项目的目的是检测2-抗纤溶酶（2-AP）基因内单核苷酸多态性（SNP）的频率。该SNP导致2-AP长链6位的一个氨基酸从精氨酸(R)变为色氨酸(W)。我们的目的是确定SNP在一般人群中的频率，并确定其如何影响a2-AP水平、蛋白质序列和体外凝血措施。

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.