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CRP Gene Polymorphisms Associated with Differences in Blood CRP and Disease Risk
Alexander J. Szalai

It has long been recognized that environmental and intrinsic variables like smoking, infections, age, gender, obesity, lipid levels, blood pressure, etc. all contribute to variation in baseline CRP level (1)- but more recent evidence indicates an additional and substantial genetic component (1-3). The realization that CRP genetic polymorphisms do exist and that certain of these directly and predictably influence steady-state blood CRP level is of substantial clinical importance, because genetic predisposition could account for a significant proportion of people with higher-than-average baseline CRP and thus their higher-than-average risk of heart disease (4).

In his presentation Dr. Szalai will review the published evidence showing that various CRP gene polymorphisms are associate with blood CRP levels, that certain polymorphisms are functional and thus directly impact CRP blood levels, and that some CRP genetic variations are associated to heart and blood vessel disease. The presentation will necessarily be limited to discussion of CRP genetics per se, a field of study which began in earnest just over 20 years ago when the CRP gene was mapped to chromosome 1 and its DNA sequence deciphered. The heritable nature of CRP blood levels and the contribution to this heritability made by the most informative and functional CRP gene sequence variations (to date 41 such variations have been identified (5)) will be discussed. The possibility that genetic screening for CRP gene expression variants could help categorize patients into groups at high versus low future risk of cardiovascular disease will be considered.

References

  1. Kushner I, Rzewnicki D, and Samols D. 2006. What does minor elevation of C-reactive protein signify? Am J Med 119: 166.e17-166.e28
  2. Kluft C and de Maat MPM. 2003. Genetics of C-reactive protein. New possibilities and complications. Arterioscler Thromb Vasc Biol 23:1956-1959
  3. Kathiresan S, Larson MG, Vasan RS, Chao-Yu G, Gona P, Keaney JF Jr., et al. 2006. Contribution of clinical correlates and 13 C-reactive protein gene polymorphisms to interindividual variability in serum C-reactive protein level. Circulation 113:1415-1423
  4. Hingorani AD, Shah T, and Casas JP. 2006. Linking observational and genetic approaches to determine the role of C-reactive protein in heart disease risk. Eur Heart J Advanced Access published May 9, 2006
  5. Crawford DC, Yi Q, Smith JD, Shephard C, Wong M, Witrak L, et al. 2006. Allelic spectrum of the natural variation in CRP. Hum Genet 119:496-504

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