C-reactive protein gene polymorphisms in disease susceptibility and clinical manifestations of Korean systemic lupus erythematosus.

Abstract

OBJECTIVE: C-reactive protein (CRP) is a sensitive marker of inflammation. It is hypothesized that polymorphism of CRP gene contributes to susceptibility to systemic lupus erythematosus (SLE). We tested this hypothesis by identifying CRP gene polymorphisms in Korean patients with SLE.

METHODS: Approximately 1.5 kb of CRP promoter region was screened for single nucleotide polymorphism (SNP) using direct sequencing and 3 SNP in CRP exons by restriction fragment length polymorphism. The basal levels of CRP were measured by immunoturbidimetry. The effect of -390 C>A or T polymorphism on the promoter activity was analyzed by luciferase reporter assay in Hep3B cells.

RESULTS: Allele frequency at polymorphisms within CRP promoter and exon in our Korean patients with SLE differed from that of Caucasians. The A allele was a major allele at position 2043 in Korean SLE patients, whereas G is a major allele in Caucasian SLE. Our SLE patients had minor allele in the -390 polymorphism more frequently versus controls (p = 0.033). CRP 1185 polymorphism was associated with thrombocytopenia (p = 0.043). The basal levels of CRP were significantly higher in individuals who had minor allele in -390 and 2043 polymorphisms (p = 0.03. p = 0.024, respectively). Promoter-reporter construct carrying the -390 A or T allele displayed significantly higher promoter activity than that with the -390 C allele (p < 0.001).

CONCLUSION: CRP gene -390 polymorphism plays a role in disease susceptibility of SLE through regulation of serum CRP level. Our results suggest that elevated basal CRP level may be important in the pathogenesis of SLE, even though CRP responsiveness to noninfectious inflammation of SLE is decreased.