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NDT Advance Access published online on May 6, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp210
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© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


A candidate gene approach to genetic prognostic factors of IgA nephropathy—a result of Polymorphism REsearch to DIstinguish genetic factors Contributing To progression of IgA Nephropathy (PREDICT-IgAN)

Ryohei Yamamoto1, Yasuyuki Nagasawa1, Tatsuya Shoji2, Kazunori Inoue2, Takuya Uehata2, Tetsuya Kaneko2, Tomonori Okada2, Atsushi Yamauchi3, Yoshiharu Tsubakihara2, Enyu Imai1, Yoshitaka Isaka4 and Hiromi Rakugi1

1 Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine 2 Department of Kidney Disease and Hypertension, Osaka General Medical Center 3 Division of Nephrology, Department of Internal Medicine, Osaka Rosai Hospital 4 Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka, Japan

Correspondence and offprint requests to: Yasuyuki Nagasawa; E-mail: nagasawa{at}kid.med.osaka-u.ac.jp



  Abstract

Background. Renal prognosis of IgA nephropathy (IgAN) is affected by environmental and genetic factors. Other studies demonstrated that some atherosclerotic disease-related genes were significantly associated with renal prognosis.

Methods. The Polymorphism REsearch to DIstinguish genetic factors Contributing To progression of IgAN (PREDICT-IgAN) was a multicentre retrospective observational study to investigate associations between progression of IgAN (a 50% increase of serum creatinine level and slope of eGFR) and a hundred atherosclerotic disease-related gene polymorphisms, mainly single nucleotide polymorphisms (SNPs) in 320 IgAN patients who had more than a normal range of urinary protein (≥0.25 g/day) at diagnosis.

Results. During 8.3 ± 4.2 years of a follow-up period, 83 patients (25.9%) developed progression. In log-rank tests, glycoprotein Ia GPIa C807T and G873A and intercellular adhesion molecule-1 ICAM-1 A1548G (K469E) were found to be significantly associated with progression even after adjustment for multiple comparisons by the method of Bonferroni (adjusted P = 0.0174, 0.0176 and 0.0430, respectively). In a multivariate Cox proportional-hazards model, GPIa 807TT (873CC) [versus 807TT, adjusted hazard ratio 2.05 (95% confidence interval 1.13–3.71)] and ICAM-1 1548GG [versus 1548AA, 2.55 (1.40–4.65)] were identified as independent genetic predictors of progression, along with conventional clinical prognostic factors such as eGFR, urinary protein and use of antihypertensives at diagnosis.

Conclusions. PREDICT-IgAN distinguished GPIa C807T/ G873A and ICAM-1 A1548G from multiple athero- sclerotic disease-related gene polymorphisms by their predictive indicator for progression of IgAN.

Keywords: genetic prognostic factor; glycoprotein Ia GPIa; IgA nephropathy; intercellular adhesion molecule-1 ICAM-1; single nucleotide polymorphism (SNP)

Received for publication: 6.12.08
Accepted in revised form: 15. 4.09


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