Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and is characterized by extremely variable clinical and morphological features and outcome. TGF-beta1 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-beta1 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-beta1 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-beta1, collagen IV and alpha-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-beta1 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-beta1 COD 10 C/T polymorphism seems to be associated with more severe histological lesions, higher renal TGF-beta1 mRNA levels and a worse prognosis. This polymorphism seems to be functionally relevant and to have a prognostic impact.

Primary IgA nephropathy is more severe in TGF-beta1 high secretor patients / Brezzi, B; Del Prete, D; Lupo, A; Magistroni, Riccardo; Gomez Lira, M; Bernich, P; Anglani, F; Mezzabotta, F; Turco, A; Furci, L; Ceol, M; Antonucci, F; Abaterusso, C; Bonfante, L; D'Angelo, A; Albertazzi, Alberto; Gambaro, G.. - In: JN. JOURNAL OF NEPHROLOGY. - ISSN 1121-8428. - STAMPA. - 22:6(2009), pp. 747-759.

Primary IgA nephropathy is more severe in TGF-beta1 high secretor patients.

MAGISTRONI, Riccardo;ALBERTAZZI, Alberto;
2009

Abstract

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and is characterized by extremely variable clinical and morphological features and outcome. TGF-beta1 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-beta1 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-beta1 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-beta1, collagen IV and alpha-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-beta1 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-beta1 COD 10 C/T polymorphism seems to be associated with more severe histological lesions, higher renal TGF-beta1 mRNA levels and a worse prognosis. This polymorphism seems to be functionally relevant and to have a prognostic impact.
2009
22
6
747
759
Primary IgA nephropathy is more severe in TGF-beta1 high secretor patients / Brezzi, B; Del Prete, D; Lupo, A; Magistroni, Riccardo; Gomez Lira, M; Bernich, P; Anglani, F; Mezzabotta, F; Turco, A; Furci, L; Ceol, M; Antonucci, F; Abaterusso, C; Bonfante, L; D'Angelo, A; Albertazzi, Alberto; Gambaro, G.. - In: JN. JOURNAL OF NEPHROLOGY. - ISSN 1121-8428. - STAMPA. - 22:6(2009), pp. 747-759.
Brezzi, B; Del Prete, D; Lupo, A; Magistroni, Riccardo; Gomez Lira, M; Bernich, P; Anglani, F; Mezzabotta, F; Turco, A; Furci, L; Ceol, M; Antonucci, ...espandi
File in questo prodotto:
File Dimensione Formato  
747-759 GAMBARO.pdf

Accesso riservato

Tipologia: Versione pubblicata dall'editore
Dimensione 473.78 kB
Formato Adobe PDF
473.78 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/629918
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 14
social impact