TY - JOUR
T1 - Primary IgA nephropathy is more severe in TGF-β1 high secretor patients
AU - Brezzi, Brigida
AU - Del Prete, Dorella
AU - Lupo, Antonio
AU - Magistroni, Riccardo
AU - Gomez-Lira, Macarena
AU - Bernich, Patrizia
AU - Anglani, Franca
AU - Mezzabotta, Federica
AU - Turco, Alberto
AU - Furci, Luciana
AU - Ceol, Monica
AU - Bonfante, Luciana
AU - D'Angelo, Angela
AU - Albertazzi, Alberto
AU - Gambaro, Giovanni
PY - 2009
Y1 - 2009
N2 - Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and is characterized by extremely variable clinical and morphological features and outcome. TGF-β1 has a key role in fibrogenesis and the progression of renal damage. Its production is under genetic control. Methods: We recruited 105 Italian biopsy-proven IgAN patients for genotyping for the TGF-β1 C-509T, T869C (COD 10) and G915C (COD 25) polymorphisms; 200 healthy blood donors were used as normal controls. Glomerular and interstitial mRNA levels of TGF-β1 were assessed by real-time PCR in 34 patients to seek relationships with clinical, renal histopathological features and outcome. Results: The genotype distributions in the IgAN population were not statistically different from the controls. The COD 10 TT genotype was associated with more severe histological damage as assessed by Lee's classification (CC 50%, CT 39.6% and TT 17.2% were graded as mild; CC 35.7%, CT 43.7% and TT 44.8% as moderate, and CC 14.3%, CT 16.7% and TT 37.9% as severe [p=0.0049]) and with severe interstitial infiltrates (CC 10.4%, CT 35.2% and TT 54.2% [p=0.03]). A higher interstitial immunodeposition was observed for TGF-β1, collagen IV and a-SMA in patients with the COD 10 T allele (p=0.045, p=0.049, p=0.032, respectively). The T allele was associated with significantly higher TGF-β1 mRNA levels in the interstitium (TT+CT vs. CC: 0.52 ± 0.16 vs. 0.18 ± 0.10 copies/mL, respectively; p=0.000). The T allele was also associated with higher mRNA levels in glomeruli, though the difference was not statistically significant. Finally, the T allele was significantly associated with a worse prognosis, the end points being reached by 40% of TT+CT and 32% of CC patients (p=0.009). Conclusions: In primary IgA nephropathy, the T allele of the TGF-β1 COD 10 C/T polymorphism seems to be associated with more severe histological lesions, higher renal TGF-β1 mRNA levels and a worse prognosis. This polymorphism seems to be functionally relevant and to have a prognostic impact.
AB - Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and is characterized by extremely variable clinical and morphological features and outcome. TGF-β1 has a key role in fibrogenesis and the progression of renal damage. Its production is under genetic control. Methods: We recruited 105 Italian biopsy-proven IgAN patients for genotyping for the TGF-β1 C-509T, T869C (COD 10) and G915C (COD 25) polymorphisms; 200 healthy blood donors were used as normal controls. Glomerular and interstitial mRNA levels of TGF-β1 were assessed by real-time PCR in 34 patients to seek relationships with clinical, renal histopathological features and outcome. Results: The genotype distributions in the IgAN population were not statistically different from the controls. The COD 10 TT genotype was associated with more severe histological damage as assessed by Lee's classification (CC 50%, CT 39.6% and TT 17.2% were graded as mild; CC 35.7%, CT 43.7% and TT 44.8% as moderate, and CC 14.3%, CT 16.7% and TT 37.9% as severe [p=0.0049]) and with severe interstitial infiltrates (CC 10.4%, CT 35.2% and TT 54.2% [p=0.03]). A higher interstitial immunodeposition was observed for TGF-β1, collagen IV and a-SMA in patients with the COD 10 T allele (p=0.045, p=0.049, p=0.032, respectively). The T allele was associated with significantly higher TGF-β1 mRNA levels in the interstitium (TT+CT vs. CC: 0.52 ± 0.16 vs. 0.18 ± 0.10 copies/mL, respectively; p=0.000). The T allele was also associated with higher mRNA levels in glomeruli, though the difference was not statistically significant. Finally, the T allele was significantly associated with a worse prognosis, the end points being reached by 40% of TT+CT and 32% of CC patients (p=0.009). Conclusions: In primary IgA nephropathy, the T allele of the TGF-β1 COD 10 C/T polymorphism seems to be associated with more severe histological lesions, higher renal TGF-β1 mRNA levels and a worse prognosis. This polymorphism seems to be functionally relevant and to have a prognostic impact.
KW - Codon 10 polymorphism
KW - ESRD
KW - IgA nephropathy
KW - TGF-β1
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M3 - Article
C2 - 19967654
AN - SCOPUS:72149087957
VL - 22
SP - 747
EP - 759
JO - Journal of Nephrology
JF - Journal of Nephrology
SN - 1121-8428
IS - 6
ER -