C-reactive protein gene polymorphisms influence susceptibility and outcomes of biopsy-proven giant cell arteritis in Italian patients.

ABSTRACT

OBJECTIVES: To investigate potential associations between the two functional C-reactive protein (CRP) gene polymorphisms at position 3872C>T (rs1205) and 4741G>C (rs3093068) and susceptibility, clinical expression, laboratory and pathological findings, and outcomes of giant cell arteritis (GCA) in a Nothern Italian population. METHODS: One hundred and seventy Italian patients with biopsy-proven GCA resident in Reggio Emilia area, Italy, and 200 healthy controls from the same geographic area were genotyped for rs1205 and rs3093068 CRP gene polymorphisms by molecular methods. The patients were subgrouped on the basis of the presence or absence of clinical manifestations, histological and laboratory findings, and outcomes. RESULTS: The distribution of rs1205 genotype was significantly different between GCA patients and controls (p=0.018). Homozygosity for T allele was significantly more frequent in GCA patients compared to controls [p=0.006; odds ratio (OR) 2.28 (95% CI 1.1, 4.8)]. The distribution of rs3093068 genotype differed significantly between GCA patients and controls (p=0.010). Allele C and the carriers of the C allele (C/C+C/G) of rs3093068 genotype were significantly less frequent in GCA patients compared to controls [p=0.002, OR 0.39 (95% CI 0.24-0.73); p=0.002, OR 0.35 (95% CI 0.17-0.70), respectively]. No significant associations were found between the two polymorphisms and baseline clinical manifestations. The carriers of the allele C of rs3093068 genotype had significantly higher CRP values at diagnosis (13.2±5.0 vs. 8.3±6.0 mg/dl, p=0.007). Homozygosity for T allele of rs1205 genotype had a significantly more frequent eosinophil infiltration of the temporal artery wall (21.4% vs. 6.0%) (p=0.010, OR 4.28;1.31-13.98) than patients carrying the allele C. Carriers of the allele T of rs1205 genotype had lower glucocorticoid (GC) treatment duration (p=0.041), lower cumulative total GC dose (p=0.017), and higher prevalence of long-term remission (p=0.024). CONCLUSIONS: CRP gene rs1205 and rs3093068 polymorphisms influence GCA susceptibility and its outcomes.