|Title||Genetic variants in PLG, LPA and SIGLEC 14 as well as smoking contribute to plasma plasminogen levels.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Ma Q, Ozel AB, Ramdas S, McGee B, Khoriaty R, Siemieniak D, Li H-D, Guan Y, Brody LC, Mills JL, Molloy AM, Ginsburg D, Li JZ, Desch KC|
|Date Published||2014 Sep 10|
Plasminogen is the precursor of the serine protease plasmin, a central enzyme of the fibrinolytic system. Plasma levels of plasminogen vary by almost two-fold among healthy individuals, yet little is known about its heritability or genetic determinants in the general population. In order to identify genetic factors affecting the natural variation of plasminogen levels, we performed a genome-wide association study and linkage analysis in a sample of 3,456 young healthy individuals who participated in the Genes and Blood Clotting Study (GABC) or the Trinity Student Study (TSS). Heritability of plasminogen levels was 48.1% - 60.0%. Tobacco smoking and female sex were associated with higher levels of plasminogen. In the meta-analysis, eleven SNPs in two regions reached genome-wide significance (P < 5.0E-8). Of these, nine SNPs were near the PLG or LPA genes on Chr6q26, while two were on Chr19q13 and 5'-upstream of SIGLEC14. These 11 SNPs represented 4 independent signals and collectively explained 6.8% of plasminogen level variation in the study populations. The strongest association was observed for a non-synonymous SNP in the PLG gene (R523W). Individuals bearing an additional copy of this allele had an average of 13.4% decrease in plasma plasminogen level.