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

 
TitleGenetic markers associated with plasma protein C level in African Americans: the atherosclerosis risk in communities (ARIC) study.
Publication TypeJournal Article
Year of Publication2014
AuthorsM Munir, S, Weng, L-C, Tang, W, Basu, S, Pankow, JS, Matijevic, N, Cushman, M, Boerwinkle, E, Folsom, AR
JournalGenet Epidemiol
Volume38
Issue8
Pagination709-13
Date Published2014 Dec
ISSN1098-2272
KeywordsAfrican Americans, Atherosclerosis, Female, Genetic Markers, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Protein C, Risk
Abstract

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 Atherosclerosis 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 rs867186 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 (β = 0.49 μg/ml; 10% variance explained). In the 2q14 region, the top SNPs were near or within the PROC gene: rs7580658 (β = 0.15 μg/ml; 2% variance explained, P = 1.7 × 10(-12) ) and rs1799808 (β = 0.15 μg/ml; 2% variance explained, P = 2.03 × 10(-12) ). These two SNPs were in strong linkage disequilibrium (LD) with another SNP rs1158867 that resides in a biochemically functional site and in weak to strong LD with the top PROC variants previously reported in individuals of European descent. In addition, two variants outside the PROC region were significantly and independently associated with protein C levels: rs4321325 in CYP27C1 and rs13419716 in MYO7B. In summary, this first GWA study for plasma protein C levels in African Americans confirms the associations of SNPs in the PROC and PROCR regions with circulating levels of protein C across ethnic populations and identifies new candidates for protein C regulation.

DOI10.1002/gepi.21868
Alternate JournalGenet. Epidemiol.
PubMed ID25376901
PubMed Central IDPMC4354842
Grant ListHHSN268200625226C / / PHS HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100010C / / PHS HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
HHSN268201100012C / / PHS HHS / United States
N01 HC065226 / HC / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
R01 HL095603 / HL / NHLBI NIH HHS / United States
R01-HL095603 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States