Publication Date:
2010-12-02
Description:
Protein C is an important endogenous anticoagulant in hemostasis. Deficiencies of protein C due to genetic mutations or a low level of circulating protein C increase the risk of venous thromboembolism. We performed a genome-wide association scan for plasma protein C antigen concentration with approximately 2.5 million single-nucleotide polymorphisms in 8048 individuals of European ancestry and a replication analysis in a separate sample of 1376 individuals in the Atherosclerosis Risk in Communities Study. Four independent loci from 3 regions were identified with genome-wide significance: 2p23 (GCKR, best SNP rs1260326, P = 2.04 × 10−17), 2q13-q14 (PROC, rs1158867, P = 3.77 × 10−36), 20q11 (near and within PROCR, rs8119351, P = 2.68 × 10−203), and 20q11.22 (EDEM2, rs6120849, P = 7.19 × 10−37 and 5.23 × 10−17 before and after conditional analysis, respectively). All 4 loci replicated in the independent sample. Furthermore, pooling the discovery and replication sets yielded an additional locus at chromosome 7q11.23 (BAZ1B, rs17145713, P = 2.83 × 10−8). The regions marked by GCKR, EDEM2, and BAZ1B are novel loci that have not been previously reported for association with protein C concentration. In summary, this first genome-wide scan for circulating protein C concentration identified both new and known loci in the general population. These findings may improve the understanding of physiologic mechanisms in protein C regulation.
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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