1059G/C polymorphism within the exon 2 of the C-reactive protein gene: relationship to C-reactive protein levels and prognosis in unstable angina.

OBJECTIVE

Patients with unstable angina (UA) and high C-reactive protein (CRP) have increased cardiovascular risk. Whether genetic factors such as the synonymous 1059G/C polymorphism within the exon 2 of the human CRP gene determine CRP levels and outcome is unclear.

METHODS

In 105 consecutive patients with UA, we assessed the CRP 1059G/C polymorphism, CRP plasma levels and interleukin-6 production after in-vitro stimulation of whole blood with lipopolysaccharide (1 ng/ml). Coronary events during a 24-month follow-up were recorded.

RESULTS

CRP levels (median, range) were significantly lower among C-allele carriers (2.3 mg/l, 0.5-26.9) than among GG homozygotes (5.9 mg/l, 0.8-72.12, P=0.009). Interleukin-6 production was lower in C-allele carriers (1645 pg/ml, 832.0-9522) than in GG homozygotes (3929 pg/ml, 670.8-10 582), (P=0.085). At follow-up, 1059C-allele carriers experienced fewer coronary events than 1059GG homozygotes (13 vs. 47%, P=0.021). At multivariable analysis, a CRP level >3 mg/l, but not the 1059G/C polymorphism, was an independent predictor of coronary events (odds ratio 10.04, 95% confidence interval 2.84-35.44, P=0.0002).

CONCLUSION

This study shows that the CRP synonymous 1059G/C polymorphism affects CRP levels. No independent association was, however, observed between this polymorphism and clinical outcome in UA.