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).
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 (> or =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.
Yamamoto
Ryohei
R
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
Nagasawa
Yasuyuki
Y
Shoji
Tatsuya
T
Inoue
Kazunori
K
Uehata
Takuya
T
Kaneko
Tetsuya
T
Okada
Tomonori
T
Yamauchi
Atsushi
A
Tsubakihara
Yoshiharu
Y
Imai
Enyu
E
Isaka
Yoshitaka
Y
Rakugi
Hiromi
H
D000328:Adult; D018450:Disease Progression; D005260:Female; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D012189:Retrospective Studies