Aims: Clara cell secretory protein (CC16) is a protein with anti-inflammatory and immunomodulatory properties. Moreover, both CC16 gene knockout and antisense-transgenic mouse models developed glomerulonephritis resembling IgA nephropathy (IgAN). In the present study, we evaluated the influence of the G38A polymorphism in the CC16 gene exon 1 on the development and progression of IgAN.
Methods: Korean patients with biopsy-proven IgAN (n=267) with a minimal follow-up of 4 years (mean +/- SD 103.8 +/- 52.6 months) were recruited. Healthy normal subjects (n=315) were included as controls. The G38A polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism method.
Results: GG, GA and AA genotype frequencies were 36.3, 50.2 and 13.5% in IgAN patients, respectively, and 34.3, 50.2 and 15.5% in controls (chi2 = 0.596, p = 0.742). The G allele frequency was 0.614 in IgAN patients and 0.594 in controls (chi2 = 0.429, p = 0.512). Moreover, the GG genotype frequencies were 40.4% in patients showing stable disease course and 26.6% in those with progressive disease (chi2 = 4.029, p = 0.045). Patients with the GG genotype showed a better outcome by Kaplan-Meier analysis in terms of renal survival (p = 0.043). The CC16 polymorphism remained an independent risk factor for progression after multivariate analysis (Cox regression model, HR for CC16 AA genotype: 2.34, 95% CI 1.19-4.64, p = 0.014).
Conclusion: Our results suggest that CC 16 gene G38A polymorphism is not associated with the development of IgAN, but that it is an important marker of progression in IgAN.