Format

Send to:

Choose Destination
See comment in PubMed Commons below
BMJ. 2011 Feb 15;342:d548. doi: 10.1136/bmj.d548.

Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data.

Collaborators (157)

Eiriksdottir G, Harris TB, Launer LJ, Gudnason V, Folsom AR, Andrews G, Ballantyne CM, Samani NJ, Hall AS, Braund PS, Balmforth AJ, Whincup PH, Morris R, Lawlor DA, Lowe GD, Timpson N, Ebrahim S, Ben-Shlomo Y, Davey-Smith G, Timpson N, Nordestgaard BJ, Tybjærg-Hansen A, Zacho J, Brown M, Sandhu M, Ricketts SL, Ashford S, Lange L, Reiner A, Cushman M, Tracy R, Wu C, Ge J, Zou Y, Sun A, Hung J, McQuillan B, Thompson P, Beilby J, Warrington N, Palmer LJ, Wanner C, Drechsler C, Hoffmann MM, Fowkes FG, Lowe GD, Tzoulaki I, Kumari M, Miller M, Marmot M, Onland-Moret C, van der Schouw YT, Boer JM, Wijmenga C, Ricketts SL, Ashford S, Sandhu M, Khaw KT, Vasan RS, Schnabel RB, Yamamoto JF, Benjamin EJ, Schunkert H, Erdmann J, König IR, Hengstenberg C, Chiodini B, Franzosi MG, Pietri S, Gori F, Rudock M, Liu Y, Lohman K, Harris TB, Humphries SE, Hamsten A, Norman PE, Hankey GJ, Jamrozik K, Palmer LJ, Rimm EB, Pai JK, Psaty BM, Heckbert SR, Bis JC, Yusuf S, Anand S, Engert JC, Xie C, Collins R, Clarke R, Bennett D, Kooner J, Chambers J, Elliott P, März W, Kleber ME, Böhm BO, Winkelmann BR, Melander O, Berglund G, Koenig W, Thorand B, Baumert J, Peters A, Rimm EB, Manson J, Pai JK, Humphries SE, Cooper JA, Talmud PJ, Ladenvall P, Johansson L, Jansson JH, Hallmans G, Reilly MP, Qu L, Li M, Rader DJ, Watkins H, Clarke R, Hopewell J, Saleheen D, Danesh J, Frossard P, Sattar N, Robertson M, Shepherd J, Schaefer E, Hofman A, Witteman JC, Kardys I, Dehghan A, de Faire U, Bennet A, Gigante B, Leander K, Ben-Shlomo Y, Davey-Smith G, Timpson N, Peters B, Maitland-van der Zee AH, de Boer A, Klungel O, Reiner A, Manson J, Greenland P, Dai J, Liu S, Kumari M, Brunner E, Kivimaki M, Marmot M, Sattar N, O'Reilly D, Ford I, Packard CJ.

Abstract

OBJECTIVE:

To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease.

DESIGN:

Mendelian randomisation meta-analysis of individual participant data from 47 epidemiological studies in 15 countries.

PARTICIPANTS:

194 418 participants, including 46 557 patients with prevalent or incident coronary heart disease. Information was available on four CRP gene tagging single nucleotide polymorphisms (rs3093077, rs1205, rs1130864, rs1800947), concentration of C reactive protein, and levels of other risk factors.

MAIN OUTCOME MEASURES:

Risk ratios for coronary heart disease associated with genetically raised C reactive protein versus risk ratios with equivalent differences in C reactive protein concentration itself, adjusted for conventional risk factors and variability in risk factor levels within individuals.

RESULTS:

CRP variants were each associated with up to 30% per allele difference in concentration of C reactive protein (P<10(-34)) and were unrelated to other risk factors. Risk ratios for coronary heart disease per additional copy of an allele associated with raised C reactive protein were 0.93 (95% confidence interval 0.87 to 1.00) for rs3093077; 1.00 (0.98 to 1.02) for rs1205; 0.98 (0.96 to 1.00) for rs1130864; and 0.99 (0.94 to 1.03) for rs1800947. In a combined analysis, the risk ratio for coronary heart disease was 1.00 (0.90 to 1.13) per 1 SD higher genetically raised natural log (ln) concentration of C reactive protein. The genetic findings were discordant with the risk ratio observed for coronary heart disease of 1.33 (1.23 to 1.43) per 1 SD higher circulating ln concentration of C reactive protein in prospective studies (P=0.001 for difference).

CONCLUSION:

Human genetic data indicate that C reactive protein concentration itself is unlikely to be even a modest causal factor in coronary heart disease.

PMID:
21325005
[PubMed - indexed for MEDLINE]
PMCID:
PMC3039696
Free PMC Article

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk