Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/53925
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: The association of C-reactive protein and CRP genotype with coronary heart disease: findings from five studies with 4610 cases amongst 18637 participants
Author: Lawlor, D.
Harbord, R.
Timpson, N.
Lowe, G.
Rumley, A.
Gaunt, T.
Baker, I.
Yarnell, J.
Kivimaki, M.
Kumari, M.
Norman, P.
Jamrozik, K.
Hankey, G.
Almeida, O.
Flicker, L.
Warrington, N.
Marmot, M.
Ben-Shlomo, Y.
Palmer, L.
Day, I.
et al.
Citation: PLoS One, 2008; 3(8):1-14
Publisher: Public Library of Science
Issue Date: 2008
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Debbie A. Lawlor, Roger M. Harbord, Nic J. Timpson, Gordon D. O. Lowe, Ann Rumley, Tom R. Gaunt, Ian Baker, John W. G. Yarnell, Mika Kivimäki, Meena Kumari, Paul E. Norman, Konrad Jamrozik, Graeme J. Hankey, Osvaldo P. Almeida, Leon Flicker, Nicole Warrington, Michael G. Marmot, Yoav Ben-Shlomo, Lyle J. Palmer, Ian N. M. Day, Shah Ebrahim and George Davey Smith
Abstract: Background It is unclear whether C-reactive protein (CRP) is causally related to coronary heart disease (CHD). Genetic variants that are known to be associated with CRP levels can be used to provide causal inference of the effect of CRP on CHD. Our objective was to examine the association between CRP genetic variant +1444C>T (rs1130864) and CHD risk in the largest study to date of this association. Methods and Results We estimated the association of CRP genetic variant +1444C>T (rs1130864) with CRP levels and with CHD in five studies and then pooled these analyses (N = 18,637 participants amongst whom there were 4,610 cases). CRP was associated with potential confounding factors (socioeconomic position, physical activity, smoking and body mass) whereas genotype (rs1130864) was not associated with these confounders. The pooled odds ratio of CHD per doubling of circulating CRP level after adjustment for age and sex was 1.13 (95%CI: 1.06, 1.21), and after further adjustment for confounding factors it was 1.07 (95%CI: 1.02, 1.13). Genotype (rs1130864) was associated with circulating CRP; the pooled ratio of geometric means of CRP level among individuals with the TT genotype compared to those with the CT/CC genotype was 1.21 (95%CI: 1.15, 1.28) and the pooled ratio of geometric means of CRP level per additional T allele was 1.14 (95%CI: 1.11, 1.18), with no strong evidence in either analyses of between study heterogeneity (I2 = 0%, p>0.9 for both analyses). There was no association of genotype (rs1130864) with CHD: pooled odds ratio 1.01 (95%CI: 0.88, 1.16) comparing individuals with TT genotype to those with CT/CC genotype and 0.96 (95%CI: 0.90, 1.03) per additional T allele (I2<7.5%, p>0.6 for both meta-analyses). An instrumental variables analysis (in which the proportion of CRP levels explained by rs1130864 was related to CHD) suggested that circulating CRP was not associated with CHD: the odds ratio for a doubling of CRP level was 1.04 (95%CI: 0.61, 1.80). Conclusions We found no association of a genetic variant, which is known to be related to CRP levels, (rs1130864) and having CHD. These findings do not support a causal association between circulating CRP and CHD risk, but very large, extended, genetic association studies would be required to rule this out.
Keywords: Humans; Coronary Disease; C-Reactive Protein; Retrospective Studies; Confounding Factors (Epidemiology); Genotype; Polymorphism, Single Nucleotide; Aged; Middle Aged; Female; Genetic Variation
Rights: © 2008 Lawlor et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0020084642
DOI: 10.1371/journal.pone.0003011
Grant ID: http://purl.org/au-research/grants/nhmrc/279408
http://purl.org/au-research/grants/nhmrc/379600
http://purl.org/au-research/grants/nhmrc/458505
Appears in Collections:General Practice publications

Files in This Item:
File Description SizeFormat 
hdl_53925.pdfPublished version404.56 kBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.