The objective of this study is to perform comprehensive genetic studies on a biological and positional candidate gene for systemic erythematosus (SLE) that codes for coagulation factor II or prothrombin (F2). We will resequence the entire F2 gene in selected SLE patients and controls and then to examine the role of this sequence variation in relation to SLE and the risk of coronary heart disease (CHD) in SLE patients. Following are the specific aims: Aim 1) resequence the entire F2 gene (21.3 kb) to identify common and rare putative functional variants in 100 SLE patients positive for both APA and CHD and 100 selected normal subjects having high titers of APA in order to create a high-density map of SNPs in the F2 gene and then to use this data in subsequent aims. Aim 2) screen rare variants and tagSNPs of common variants in the entire case-control sample available to us (577 cases, 677 controls;80.5% U.S. white, 19.5% U.S. black) to determine their distributions. The data from the rare and common tagSNPs will be used in Aims 3 and 4 for genotype-phenotype analyses to test the hypotheses of "common trait - rare variant" and "common trait - common variant", respectively. Aim 3) evaluate the relationship between F2 genetic variants and SLE risk and quantitative traits, including F2 activity, the occurrence of APA [anti-apoH, anti-cardiolipin (ACL), lupus anticoagulant (LAC), anti-oxidized phospholipids (anti-oxPL) and anti- F2] and LDL oxidation parameters [oxidized LDL (oxLDL), antibodies against oxLDL (anti-oxLDL) and LDL immune complexes], and Aim 4) examine the relationship between F2 genetic variation and the occurrence of subclinical cardiovascular disease in SLE patients and subsets of SLE patients by the presence or absence of APA and anti-oxLDL.