NEW YORK (Reuters Health) - A polymorphism designated +1444C>T in the C-reactive protein (CRP) gene influences CRP levels, according to a new study. The authors say the findings have implications for the assessment of risk for coronary heart disease, and perhaps its pathogenesis.
“CRP concentrations are predictive of cardiovascular disease, and levels are heritable, in part,” note Dr. A.D. Hingorani, of BHF Laboratories at UCL, in London, UK, and colleagues in the November issue of Arteriosclerosis Thrombosis and Vascular Biology. They also point to several lines of evidence indicating that CRP may be more than a marker of inflammation, but rather an active promoter.
Since CRP levels seem to be a heritable trait, the researchers investigated the possibility that the human CRP gene contains polymorphisms that influence basal and stimulated CRP levels.
They measured CRP in 250 male army recruits before and after strenuous exercise and perioperatively in 193 patients undergoing coronary artery bypass graft (CABG). They identified two novel polymorphisms in the CRP gene: -717G>A and +1444C>T.
Among the army recruits, baseline CRP values were significantly higher in subjects homozygous for the +1444T allele than carriers of the +1444C allele (1.04 versus 0.55 mg/L, p = 0.014). Subjects with the TT genotype also had higher CRP levels at all time points after exercise.
In the CABG patients, mean CRP rose from 1.97 mg/L at baseline to 167.2 mg/L at 72 hours postoperatively, Dr. Hingorani and colleagues report. “Genotype did not influence mean CRP at baseline; however, peak post-CABG CRP levels were higher in +1444TT homozygous compared with +1444C-allele carriers (198 versus 164, p = 0.03).”
Whether or not CRP has a pathogenic role in coronary heart disease, levels do predict risk. The investigators point out that the new findings suggest that “there may eventually be a need to establish genotype-specific risk thresholds for CRP in the prediction of CHD risk.”
Source: Arterioscler Thromb Vasc Biol 2003;23:2063-2069. [ Google search on this article ]
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