Association between the clara cell secretory protein (CC16) G38A polymorphism and the progression of IgA nephropathy.
OBJECTIVE
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).


CONCLUSIONS
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.
Lim
C S
CS
Department of Internal Medicine, Seoul National University Boramae Hospital, Korea. cslimjy@snu.ac.kr
Kim
S M
SM
Oh
Y K
YK
Kim
Y S
YS
Chae
D W
DW
Han
J S
JS
Kim
S
S
Lee
J S
JS
Yoon
H J
HJ
D000328:Adult; D018450:Disease Progression; D005260:Female; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014598:Uteroglobin / Q000235:genetics*
C556389:SCGB1A1 protein, human; C556390:Scgb1a1 protein, mouse; D014598:Uteroglobin