A locus on chromosome 13 influences levels of TAFI antigen in healthy Mexican Americans.
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.
Warren
D M
DM
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA.
Cole
S A
SA
Dyer
T D
TD
Soria
J M
JM
Souto
J C
JC
Fontcuberta
J
J
Blangero
J
J
Maccluer
J W
JW
Almasy
L
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D025901:Carboxypeptidase B2 / Q000097:blood / Q000235:genetics* / Q000502:physiology; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D017058:Mexican Americans / Q000235:genetics*; D008875:Middle Aged; D040641:Quantitative Trait Loci / Q000235:genetics*
D025901:Carboxypeptidase B2