Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events

Leslie A. Lange, Christopher S. Carlson, Lucia A. Hindorff, Ethan M. Lange, Jeremy D Walston, J. Peter Durda, Mary Cushman, Joshua C. Bis, Donglin Zeng, Danyu Lin, Lewis H. Kuller, Deborah A. Nickerson, Bruce M. Psaty, Russell P. Tracy, Alexander P. Reiner

Research output: Contribution to journalArticle

Abstract

Context: C-reactive protein (CRP) is an inflammation protein that may play a role in the pathogenesis of cardiovascular disease (CVD). Objective: To assess whether polymorphisms in the CRP gene are associated with plasma CRP, carotid intima-media thickness (CIMT), and CVD events. Design, Setting, and Participants: In the prospective, population-based Cardiovascular Health Study, 4 tag single-nucleotide polymorphisms (SNPs) (1919A/T, 2667G/C, 3872G/A, 5237A/G) were genotyped in 3941 white (European American) participants and 5 tag SNPs (addition of 790A/T) were genotyped in 700 black (African American) participants, aged 65 years or older, all of whom were without myocardial infarction (MI) or stroke before study entry. Median follow-up was 13 years (1989-2003). Main Outcome Measures: Baseline CIMT; occurrence of MI, stroke, and CVD mortality during follow-up. Results: In white participants, 461 incident MIs, 491 incident strokes, and 490 CVD-related deaths occurred; in black participants, 67 incident MIs, 78 incident strokes, and 75 CVD-related deaths occurred. The 1919T and 790T alleles were associated with higher CRP levels in white and black participants, respectively. The 3872A allele was associated with lower CRP levels in both populations, and the 2667C allele was associated with lower CRP levels in white participants only. There was no association between CIMT and any CRP gene polymorphism in either population. In white participants, the 1919T allele was associated with increased risk of stroke for TT vs AA (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.06-1.87) and for CVD mortality (HR, 1.40; 95% CI, 1.10-1.90). In black participants, homozygosity for the 790T allele was associated with a 4-fold increased risk of MI compared with homozygosity for the 790A allele (95% CI, 1.58-10.53). The minor alleles of the 2 SNPs associated with lower plasma CRP concentration in white participants (2667C and 3872A) were associated with decreased risk of CVD mortality. Conclusions: Genetic variation in the CRP gene is associated with plasma CRP levels and CVD risk in older adults.

Original languageEnglish (US)
Pages (from-to)2703-2711
Number of pages9
JournalJournal of the American Medical Association
Volume296
Issue number22
DOIs
StatePublished - Dec 13 2006

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C-Reactive Protein
Cardiovascular Diseases
Alleles
Genes
Stroke
Carotid Intima-Media Thickness
Single Nucleotide Polymorphism
Blood Proteins
Myocardial Infarction
Confidence Intervals
Mortality
Population
African Americans
Outcome Assessment (Health Care)
Inflammation
Health

ASJC Scopus subject areas

  • Medicine(all)

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Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events. / Lange, Leslie A.; Carlson, Christopher S.; Hindorff, Lucia A.; Lange, Ethan M.; Walston, Jeremy D; Durda, J. Peter; Cushman, Mary; Bis, Joshua C.; Zeng, Donglin; Lin, Danyu; Kuller, Lewis H.; Nickerson, Deborah A.; Psaty, Bruce M.; Tracy, Russell P.; Reiner, Alexander P.

In: Journal of the American Medical Association, Vol. 296, No. 22, 13.12.2006, p. 2703-2711.

Research output: Contribution to journalArticle

Lange, LA, Carlson, CS, Hindorff, LA, Lange, EM, Walston, JD, Durda, JP, Cushman, M, Bis, JC, Zeng, D, Lin, D, Kuller, LH, Nickerson, DA, Psaty, BM, Tracy, RP & Reiner, AP 2006, 'Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events', Journal of the American Medical Association, vol. 296, no. 22, pp. 2703-2711. https://doi.org/10.1001/jama.296.22.2703
Lange, Leslie A. ; Carlson, Christopher S. ; Hindorff, Lucia A. ; Lange, Ethan M. ; Walston, Jeremy D ; Durda, J. Peter ; Cushman, Mary ; Bis, Joshua C. ; Zeng, Donglin ; Lin, Danyu ; Kuller, Lewis H. ; Nickerson, Deborah A. ; Psaty, Bruce M. ; Tracy, Russell P. ; Reiner, Alexander P. / Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events. In: Journal of the American Medical Association. 2006 ; Vol. 296, No. 22. pp. 2703-2711.
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title = "Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events",
abstract = "Context: C-reactive protein (CRP) is an inflammation protein that may play a role in the pathogenesis of cardiovascular disease (CVD). Objective: To assess whether polymorphisms in the CRP gene are associated with plasma CRP, carotid intima-media thickness (CIMT), and CVD events. Design, Setting, and Participants: In the prospective, population-based Cardiovascular Health Study, 4 tag single-nucleotide polymorphisms (SNPs) (1919A/T, 2667G/C, 3872G/A, 5237A/G) were genotyped in 3941 white (European American) participants and 5 tag SNPs (addition of 790A/T) were genotyped in 700 black (African American) participants, aged 65 years or older, all of whom were without myocardial infarction (MI) or stroke before study entry. Median follow-up was 13 years (1989-2003). Main Outcome Measures: Baseline CIMT; occurrence of MI, stroke, and CVD mortality during follow-up. Results: In white participants, 461 incident MIs, 491 incident strokes, and 490 CVD-related deaths occurred; in black participants, 67 incident MIs, 78 incident strokes, and 75 CVD-related deaths occurred. The 1919T and 790T alleles were associated with higher CRP levels in white and black participants, respectively. The 3872A allele was associated with lower CRP levels in both populations, and the 2667C allele was associated with lower CRP levels in white participants only. There was no association between CIMT and any CRP gene polymorphism in either population. In white participants, the 1919T allele was associated with increased risk of stroke for TT vs AA (hazard ratio [HR], 1.40; 95{\%} confidence interval [CI], 1.06-1.87) and for CVD mortality (HR, 1.40; 95{\%} CI, 1.10-1.90). In black participants, homozygosity for the 790T allele was associated with a 4-fold increased risk of MI compared with homozygosity for the 790A allele (95{\%} CI, 1.58-10.53). The minor alleles of the 2 SNPs associated with lower plasma CRP concentration in white participants (2667C and 3872A) were associated with decreased risk of CVD mortality. Conclusions: Genetic variation in the CRP gene is associated with plasma CRP levels and CVD risk in older adults.",
author = "Lange, {Leslie A.} and Carlson, {Christopher S.} and Hindorff, {Lucia A.} and Lange, {Ethan M.} and Walston, {Jeremy D} and Durda, {J. Peter} and Mary Cushman and Bis, {Joshua C.} and Donglin Zeng and Danyu Lin and Kuller, {Lewis H.} and Nickerson, {Deborah A.} and Psaty, {Bruce M.} and Tracy, {Russell P.} and Reiner, {Alexander P.}",
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T1 - Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events

AU - Lange, Leslie A.

AU - Carlson, Christopher S.

AU - Hindorff, Lucia A.

AU - Lange, Ethan M.

AU - Walston, Jeremy D

AU - Durda, J. Peter

AU - Cushman, Mary

AU - Bis, Joshua C.

AU - Zeng, Donglin

AU - Lin, Danyu

AU - Kuller, Lewis H.

AU - Nickerson, Deborah A.

AU - Psaty, Bruce M.

AU - Tracy, Russell P.

AU - Reiner, Alexander P.

PY - 2006/12/13

Y1 - 2006/12/13

N2 - Context: C-reactive protein (CRP) is an inflammation protein that may play a role in the pathogenesis of cardiovascular disease (CVD). Objective: To assess whether polymorphisms in the CRP gene are associated with plasma CRP, carotid intima-media thickness (CIMT), and CVD events. Design, Setting, and Participants: In the prospective, population-based Cardiovascular Health Study, 4 tag single-nucleotide polymorphisms (SNPs) (1919A/T, 2667G/C, 3872G/A, 5237A/G) were genotyped in 3941 white (European American) participants and 5 tag SNPs (addition of 790A/T) were genotyped in 700 black (African American) participants, aged 65 years or older, all of whom were without myocardial infarction (MI) or stroke before study entry. Median follow-up was 13 years (1989-2003). Main Outcome Measures: Baseline CIMT; occurrence of MI, stroke, and CVD mortality during follow-up. Results: In white participants, 461 incident MIs, 491 incident strokes, and 490 CVD-related deaths occurred; in black participants, 67 incident MIs, 78 incident strokes, and 75 CVD-related deaths occurred. The 1919T and 790T alleles were associated with higher CRP levels in white and black participants, respectively. The 3872A allele was associated with lower CRP levels in both populations, and the 2667C allele was associated with lower CRP levels in white participants only. There was no association between CIMT and any CRP gene polymorphism in either population. In white participants, the 1919T allele was associated with increased risk of stroke for TT vs AA (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.06-1.87) and for CVD mortality (HR, 1.40; 95% CI, 1.10-1.90). In black participants, homozygosity for the 790T allele was associated with a 4-fold increased risk of MI compared with homozygosity for the 790A allele (95% CI, 1.58-10.53). The minor alleles of the 2 SNPs associated with lower plasma CRP concentration in white participants (2667C and 3872A) were associated with decreased risk of CVD mortality. Conclusions: Genetic variation in the CRP gene is associated with plasma CRP levels and CVD risk in older adults.

AB - Context: C-reactive protein (CRP) is an inflammation protein that may play a role in the pathogenesis of cardiovascular disease (CVD). Objective: To assess whether polymorphisms in the CRP gene are associated with plasma CRP, carotid intima-media thickness (CIMT), and CVD events. Design, Setting, and Participants: In the prospective, population-based Cardiovascular Health Study, 4 tag single-nucleotide polymorphisms (SNPs) (1919A/T, 2667G/C, 3872G/A, 5237A/G) were genotyped in 3941 white (European American) participants and 5 tag SNPs (addition of 790A/T) were genotyped in 700 black (African American) participants, aged 65 years or older, all of whom were without myocardial infarction (MI) or stroke before study entry. Median follow-up was 13 years (1989-2003). Main Outcome Measures: Baseline CIMT; occurrence of MI, stroke, and CVD mortality during follow-up. Results: In white participants, 461 incident MIs, 491 incident strokes, and 490 CVD-related deaths occurred; in black participants, 67 incident MIs, 78 incident strokes, and 75 CVD-related deaths occurred. The 1919T and 790T alleles were associated with higher CRP levels in white and black participants, respectively. The 3872A allele was associated with lower CRP levels in both populations, and the 2667C allele was associated with lower CRP levels in white participants only. There was no association between CIMT and any CRP gene polymorphism in either population. In white participants, the 1919T allele was associated with increased risk of stroke for TT vs AA (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.06-1.87) and for CVD mortality (HR, 1.40; 95% CI, 1.10-1.90). In black participants, homozygosity for the 790T allele was associated with a 4-fold increased risk of MI compared with homozygosity for the 790A allele (95% CI, 1.58-10.53). The minor alleles of the 2 SNPs associated with lower plasma CRP concentration in white participants (2667C and 3872A) were associated with decreased risk of CVD mortality. Conclusions: Genetic variation in the CRP gene is associated with plasma CRP levels and CVD risk in older adults.

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