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)

作者：Yamamoto Ryohei; Nagasawa Yasuyuki^*; Shoji Tatsuya; Inoue Kazunori; Uehata Takuya; Kaneko Tetsuya; Okada Tomonori; Yamauchi Atsushi; Tsubakihara Yoshiharu; Imai Enyu; Isaka Yoshitaka; Rakugi Hiromi

来源：Nephrology Dialysis Transplantation, 2009, 24(12): 3686-3694.

DOI：10.1093/ndt/gfp210

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

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 atherosclerotic disease-related gene polymorphisms by their predictive indicator for progression of IgAN.

• 出版日期2009-12