Association of interleukin-10 gene G-1082A polymorphism with the progression of primary glomerulonephritis.
BACKGROUND
Interleukin-10 (IL-10) is a cytokine with immunosuppressive properties. We evaluated the influence of G-1082A polymorphism in the IL-10 gene promoter, which has been associated with modified IL-10 production, on the two most common forms of primary glomerulonephritis: IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS).


METHODS
We studied Caucasian patients (N= 191) with biopsy-proven glomerulonephritis (IgAN: N= 123, FSGS: N= 68) followed-up for 6.5 +/- 5.5 years. Patients were classified according to the slope of reciprocal serum creatinine (>/= or <-0.1 dL(*)mg(-1) (*)year(-1)) into group A (slow progressors, IgAN: N= 75, FSGS: N= 47) and group B (fast progressors, IgAN: N= 48, FSGS: N= 21). One hundred healthy volunteers were analyzed as control patients. G-1082A polymorphism was determined by polymerase chain reaction (PCR) amplification.


RESULTS
The allele frequencies were similar in patients and control group (NS). Initial renal function, proteinuria, and blood pressure did not differ significantly between patients with different genotypes. G-1082A polymorphism was associated with the progression of both IgAN and FSGS: GA/AA genotypes were more frequent in group B (fast progressors) than in group A (slow progressors; P= 0.012 for IgAN, P < 0.05 for FSGS). Patients with the GA/AA genotypes showed a worse outcome in the Kaplan-Meier analysis of renal survival (P < 0.05 for both IgAN and FSGS). The IL-10 polymorphism remained an independent risk factor for progression in multivariate analysis (Cox regression model, P < 0.05 for IgAN and FSGS).


CONCLUSIONS
Our results suggest that IL-10 gene G-1082A polymorphism is an important marker of progression in patients with IgAN and FSGS.
Bantis
Christos
C
Department of Nephrology and Rheumatology, Heinrich-Heine University, Düsseldorf, Germany.
Heering
Peter J
PJ
Aker
Sendogan
S
Klein-Vehne
Nicola
N
Grabensee
Bernd
B
Ivens
Katrin
K
D000225:Adenine; D000328:Adult; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000235:genetics / Q000503:physiopathology*; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics / Q000503:physiopathology*; D006147:Guanine; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies
D016753:Interleukin-10; D006147:Guanine; D000225:Adenine