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Plasminogen is a hemostasis-related phenotype and is commonly implicated in thrombotic and bleeding disorders. In the San Antonio Family Heart Study (SAFHS), we performed to our knowledge the first genomewide linkage scan for quantitative trait loci (QTLs) that influence the level of plasminogen. The subset of the SAFHS population used for this study consists of 629 individuals distributed across 26 extended Mexican American families. Pedigree-based variance component linkage analyses were performed using SOLAR. The mean plasminogen level was 114.94% ± 17.8 (range, 42-195). The heritability ([h.sup.2]) of plasminogen was 0.43 ± 0.08 (p < 6.3 x [10.sup.-13]). One region on chromosome 12 (12q14.1) showed suggestive evidence of linkage (LOD = 2.73, nominal p < 0.0002, genomewide p = 0.0786) near marker D12S1609. Because plasminogen has important effects in many human health problems, such as cancer and atherosclerosis, the role of this putative QTL in the regulation of plasminogen variability needs to be studied further. KEY WORDS: PLASMINOGEN, SAN ANTONIO FAMILY HEART STUDY (SAFHS), QUANTITATIVE TRAIT LOCI, MEXICAN AMERICANS., The plasminogen-plasmin proteolytic system is involved in a wide variety of biological phenomena, such as cell invasion, reproduction, embryogenesis, angiogenesis, and brain function. This system also participates in a range [...]

When activated, thrombin activatable fibrinolysis inhibitor (TAFI) inhibits fibrinolysis by modifying fibrin, depressing its plasminogen binding potential. Polymorphisms in the TAFI structural gene (CPB2) have been associated with variation in TAFI levels, but the potential occurrence of influential quantitative trait loci (QTLs) located elsewhere in the genome has been explored only in families ascertained in part through probands affected by thrombosis. We report the results of the first genome-wide linkage screen for QTLs that influence TAFI phenotypes. Data are from 635 subjects from 21 randomly ascertained Mexican American families participating in the San Antonio Family Heart Study. Potential QTLs were localized through a genome-wide multipoint linkage scan using 417 highly informative autosomal short tandem repeat markers spaced at approximately 10-cM intervals. We observed a maximum multipoint LOD score of 3.09 on chromosome 13q, the region of the TAFI structural gene. A suggestive linkage signal (LOD = 2.04) also was observed in this region, but may be an artifact. In addition, weak evidence for linkage occurred on chromosomes 17p and 9q. Our results suggest that polymorphisms in the TAFI structural gene or its nearby regulatory elements may contribute strongly to TAFI level variation in the general population, although several genes in other regions of the genome may also influence variation in this phenotype. Our findings support those of the Genetic Analysis of Idiopathic Thrombophilia (GAIT) project, which identified a potential TAFI QTL on chromosome 13q in a genome-wide linkage scan in Spanish thrombophilia families. KEY WORDS: THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR (TAFI), HEMOSTASIS, FAMILY STUDY, LINKAGE ANALYSIS, QUANTITATIVE TRAIT LOCI., Blood coagulation and fibrinolysis result from complicated physiological cascades that involve numerous hemostatic factors. In healthy individuals the balance between clot formation and dissolution is maintained by several regulatory proteins. [...]

Whole genome transcription levels are assessed in human lymphocyte sample from 1240 adults participating in the San Antonio Family Heart Study. Results support to the strategy of using lymphocyte gene expression levels as a surrogate for gene expression levels in other tissues.