Protein C is an endogenous anticoagulant protein with anti-inflammatory properties. Single-nucleotide polymorphisms (SNPs) affect the levels of circulating protein C in European Americans. We performed a genome-wide association (GWA) scan of plasma protein C concentration with approximately 2.5 million SNPs in 2,701 African Americans in the @entity731 Risk in Communities Study. Seventy-nine SNPs from the 20q11 and 2q14 regions reached the genome-wide significance threshold of 5 * 10(-8) . A missense variant @entity68359 in the PROCR gene at 20q11 is known to affect protein C levels in individuals of European descent and showed the strongest signal (P = 9.84 * 10(-65) ) in African Americans. The minor allele of this SNP was associated with higher protein C levels (b = 0.49  g/ml; 10% variance explained). In the 2q14 region, the top SNPs were near or within the @entity3790 gene: @entity68360 (b = 0.15  g/ml; 2% variance explained, P = 1.7 * 10(-12) ) and @entity68361 (b = 0.15  g/ml; 2% variance explained, P = 2.03 * 10(-12) ). These two SNPs were in strong linkage disequilibrium (LD) with another SNP @entity68362 that resides in a biochemically functional site and in weak to strong LD with the top @entity3790 variants previously reported in individuals of European descent. In addition, two variants outside the @entity3790 region were significantly and independently associated with protein C levels: @entity68363 in @entity68364 and @entity68365 in @entity68366 . In summary, this first GWA study for plasma protein C levels in African Americans confirms the associations of SNPs in the @entity3790 and PROCR regions with circulating levels of protein C across ethnic populations and identifies new candidates for protein C regulation.

Genetic markers associated with plasma protein C level in African Americans: the XXXX risk in communities (ARIC) study.

@entity68365 :: ('rs13419716', 'SNP') :: ['rs13419716'] @entity68362 :: ('rs1158867', 'SNP') :: ['rs1158867'] @entity68359 :: ('rs867186', 'SNP') :: ['rs867186'] @entity68363 :: ('rs4321325', 'SNP') :: ['rs4321325'] @entity3790 :: ('5624', 'Gene') :: ['PROC'] @entity68364 :: ('339761', 'Gene') :: ['CYP27C1'] @entity68360 :: ('rs7580658', 'SNP') :: ['rs7580658'] @entity68361 :: ('rs1799808', 'SNP') :: ['rs1799808'] @entity68366 :: ('4648', 'Gene') :: ['MYO7B'] @entity731 :: ('MESH:D050197', 'Disease') :: ['Atherosclerosis']
@entity731 :: (MESH:D050197,Disease) :: ['atherosclerosis']
