The Association of C-Reactive Protein and CRP Genotype with Coronary Heart Disease: Findings from Five Studies with 4,610 Cases amongst 18,637 Participants
Key result
The CRP genetic variant rs1130864 TT genotype was not associated with coronary heart disease compared to the CT/CC genotype (OR 1.01), suggesting no causal association between circulating CRP and CHD risk.
Why the study?
Does the CRP genetic variant +1444C>T (rs1130864), which affects circulating CRP levels, increase the risk of coronary heart disease?
Population
18,637 participants from 5 pooled studies, including 4,610 cases of coronary heart disease (CHD).
Comparison
CRP genetic variant +1444C>T and circulating CRP… vs CT/CC genotype or per additional T allele
Design
Meta-analysis
Authors
Discussion
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Implication
No role for CRP-targeted therapy in CHD; confirms noncausal relationship via Mendelian randomization meta-analysis.
Study Design
Type
Meta-Analysis (n=18,637)
Multicenter
Yes
Structured PICO
Does the CRP genetic variant +1444C>T (rs1130864), which affects circulating CRP levels, increase the risk of coronary heart disease?
P
Population
18,637 participants from 5 pooled studies, including 4,610 cases of coronary heart disease (CHD).
I
Intervention
CRP genetic variant +1444C>T (rs1130864) and circulating CRP levels
C
Comparator
CT/CC genotype (compared to TT genotype) or per additional T allele
O
Outcome
Coronary heart disease (CHD) riskhard clinical
Main Result
Effect estimate: OR 1.01 (95% CI 0.88-1.16)
Mendelian randomization analysis using the CRP genetic variant +1444C>T does not support a causal association between circulating CRP levels and coronary heart disease risk.
Limitations
- The genetic variant explains less than 1% of the variation in CRP levels, resulting in wide confidence intervals for the instrumental variables analysis
- Very large, extended genetic association studies would be required to completely rule out a causal association
- Very large, extended, genetic association studies would be required to definitively rule out a causal association
Cite This Study
Lawlor et al. (2008) conducted a meta-analysis in Coronary Heart Disease (n=18,637). CRP genetic variant +1444C>T (rs1130864) TT genotype vs. CT/CC genotype was evaluated on Coronary Heart Disease (prevalent or incident) (OR 1.01, 95% CI 0.88-1.16). The CRP genetic variant rs1130864 TT genotype was not associated with coronary heart disease compared to the CT/CC genotype (OR 1.01), suggesting no causal association between circulating CRP and CHD risk.