Impact of Polymorphism of Th1 and Proinflammatory Cytokine Genes on Development and Progression of IgA Nephropathy / 대한신장학회잡지

ABSTRACT

BACKGROUND: Cytokine gene polymorphisms regulate cytokine production. Conflicting results about the impact of several cytokines gene polymorphism on the development or progression of IgAN have been reported. We evaluated the influence of polymorphism of several Th1 and proinflammatory cytokine genes on development and progression of IgAN. METHODS: Two hundred forty patients with biopsy-proven IgAN who had a minimal follow-up of 4 years, were recruited. Patients were classified according to the slope of reciprocal serum creatinine into slow progressors (> or =-0.05 dLxmg(-1) x year(-1), N=170) and fast progressors (<-0.05 dL x mg(-1) x year(-1), N=70). Three hundred fifteen healthy subjects with normal renal function and normotension were analyzed as controls. The polymorphisms of tumor necrosis factor-alpha (TNF-alpha, G-308A), interleukin-6 (IL-6, C-634G), interferon-gamma (IFN-gamma, A874T) and interleukin-2 (IL-2, T-330G) were determined by the 5' nuclease allelic discrimination assay. RESULTS: The genotype and allele frequencies of TNF-alpha, IL-6, IFN-gamma and IL-2 were not different significantly between IgAN patients and controls. Initial renal function, amount of daily proteinuria, and frequency of hypertension did not differ significantly between IgAN patients with different genotypes of all the studied cytokines. The frequencies of genotypes of the studied cytokines did not differ according to the rate of disease progression. In Kaplan-Meier analyses, the renal survival rate did not differ significantly between IgAN patients with different genotypes of the Th1 and proinflammatory cytokines. The polymorphism of the cytokines were not an independent risk factor for the progression of IgAN in Cox regression analysis. CONCLUSIONS: Our results suggest that the polymorphism of Th1 and proinflammatory cytokines are not associated with development and progression of IgAN in Korean patients.