ABSTRACT
Objective: To analyze the association of IL-18 promoter gene polymorphisms (-607A/C and -137C/G) with disease susceptibility and manifestations of SLE patients.
Methods: Forty seven SLE patients and 50 unrelated healthy subjects (a control group) were included. All SLE patients underwent thorough clinical examination and SLE disease activity assessment using SLEDAI. The IL-18 polymorphisms were genotyped by PCR amplification and RFLP analysis while, IL- 18 plasma levels were determined by ELISA for both patients and controls.
Results: Our data indicated that the frequency of genotype -607/AC (P=0.04, OR: 2.58, 95% CI: 1.01-6.6) was significantly increased and the frequency of genotype –137/CC (P=0.049, OR: 0.27, 95% CI: 0.07-1.06) was significantly decreased in SLE patients. In addition, -607/CC genotype frequency was significantly increased in patients with serositis (X2=6.75, P=0.03) while genotype -137/GG was significantly increased in patients with arthritis/arthralgia (X2=7.06, P=0.029). Significantly elevated levels of plasma IL-18 were found in patients compared to controls (P=0.002) with significant correlation with disease activity (p <0.001). Patients with AC and CC (-607), and GG and GC (-137) genotypes have significantly higher IL-18 levels than those with AA and CC genotypes (P<0.001). Significantly higher IL-18 levels were found in control subjects with AC and CC (-607) genotypes (P=0.014).
Conclusion: Our results have provided evidence that IL18 promoter gene polymorphisms at position –607 and –137 contribute to genetic background of SLE susceptibility and presentation, as well as enhanced production of IL-18 protein in SLE patients. |