H -- Genotyping Services

THE NATIONAL INSTITUTES OF HEALTH (NIH), National Heart, Lung, and Blood Institute (NHLBI), Office of Acquisition (OA), for the National Human Genome Research Institute (NHGRI) intends to negotiate and award a contract on a sole source noncompetitive basis to the Ottawa Heart Institute Research Corporation, 40 Ruskin Street, Ontario K1Y 4W7, Canada, for genotyping of DNA samples to study the genetic susceptibility to the vascular disease, restenosis. Background / Objectives / Scope of Work The purpose of this project is to acquire information regarding genetic susceptibility to the vascular disease, in-stent restenosis. In the NHLBI DIR initially, and now in the NHGRI DIR, investigations for the CardioGene Study have been undertaken to evaluate the genomics, genetics and proteomics of restenosis. From the genetic analysis, which used a genome-wide scan, we have identified multiple candidate susceptibility loci in a case control population study design. Further genotyping is necessary for completion of the study. This will be essential to determine which, if any, identified genetic polymorphisms may confer susceptibility to restenosis. The CardioGene Study represents an opportunity to investigate the significance of basic findings regarding vascular wound healing in the disease in-stent restenosis. The lab has previously determined and investigated the significance of key cell cycle regulatory proteins, specifically the cyclin-dependent kinase inhibitors (CKIs), in regulating the repair of blood vessels following vascular injury. The lab has found that there are two major processes that occur within blood vessels following the treatment of blockages in coronary arteries with balloon angioplasty and stent placement. While dilation of the artery and placement of the stent treats the vessel blockage, it also creates a slight wound to the blood vessel. Most individuals respond well to the procedure, but approximately 25% of people treated with bare metallic stents develop a recurrence of the blockage within six months due to a regrowth of cells. This regrowth of cells narrows the artery within the stent and leads to a recurrence of clinical symptoms, called restenosis. The laboratory has defined two processes that lead to restenosis: unregulated growth of vascular smooth muscle cells and inflammation. Additional studies in the laboratory have identified the CKIs, particularly p27kip1, as major regulators of cell proliferation and inflammation. The basic research was expanded in the CardioGene Study to test these findings in the clinic. It was hypothesized that patients who fail balloon angioplasty and stent placement by developing restenosis have a genetic susceptibility that predisposes then to the disease. It is further hypothesized that these patients have abnormalities of cell cycle signaling pathways which regulate cell cycle signaling and inflammation. To understand the importance of cell cycle signaling pathways in human vascular disease, this clinical study of patients with coronary artery disease and undergoing stent therapy has been done. Approximately 460 patients were enrolled into the CardioGene Study, with 356 enrolled prospectively at the time of stent implantation and 104 cases with a history of restenosis enrolled to enrich the case group. Prospectively enrolled patients were followed for one year and divided into two groups based upon their clinical outcome: restenosis vs. no restenosis. Three sets of analyses are being conducted: (1) gene expression profiling to determine patterns of RNA expression in patients, (2) proteomics to determine patterns of protein expression in serum, and (3) genotyping using a genome-wide scan approach. From the genome wide scan, some candidate genetic loci and genes have been identified. Validation of these findings in independent cohorts of unrelated patients, for a case-control validation association analysis, will be essential for distinguishing false positives that may be obtained from a genome wide scan approach from truly associated polymorphisms that confer risk for restenosis. Further genotyping on the original CardioGene study sample will provide improved genome coverage as compared to the initial genome wide SNP assay conducted previously. As discussed below, this acquisition will require genotyping of unrelated patients who have received bare metallic stents and have restenosis outcomes after stenting determined as well as individuals with and without coronary artery disease. The information from these validation studies will be combined with the CardioGene Study to directly benefit patients in determining which patients respond best to stent placement and in developing new targets to treat restenosis. The reference number for this notice is NHLBI-PB(HG)-2008-084-KLW. The resultant acquisition will be conducted in accordance with FAR Part 15, Contracting by Negotiation and the resultant contract will include all applicable provisions and clauses in effect through the Federal Acquisition Circular 05-23. Approximately 1,200 genotyping assays are estimated for this requirement. The period of performance is seven (7) months from the date of award. The intended procurement will be classified under North American Classification System (NAICS) code applicable to this requirement is 541380 and the associated small business size standard is $ 6.5 Million. Through competitive procedures the Ottawa Heart Institute Research Corporation was awarded a purchase order to conduct the initial genotyping of DNA samples to study the genetic susceptibility to the vascular disease, restenosis for the CardioGene Study, protocol #02-H-0102. In order to maintain the continuity of the methodologies used for the initial genotyping, an award to any other source for this follow-on contract would result in a substantial duplication of cost to the Government that is not expected to be recovered through competition. This notice of intent is not a request for competitive proposals. The resulting acquisition will be entered into pursuant to the acquisition authority set forth in FAR 6.302-1 and 41 U.S.C. 253(c)(1) and HHSAR 306-302-1. Only one responsible source and no other supplies or services will satisfy agency requirements. Interested parties may identify their interest and capability to respond to the requirement or submit proposals. This notice of intent is not a request for competitive proposals. However, all proposals received within 45 days after publication of this synopsis will be considered by the Government. Responses to this notice will be reviewed in accordance with the following criteria: (1) Understanding of the Requirement and Organizational Experience. (2) Expertise and Experience of Key Personnel. (3) Genotyping Method and Throughput. A determination by the Government not to compete this proposed contract based upon responses to this notice is solely within the discretion of the Government. Information received will normally be considered solely for the purpose of determining whether to conduct a competitive procurement.