ACE insertion/deletion polymorphism (rs1799752) modifies the renoprotective effect of renin-angiotensin system blockade in patients with IgA nephropathy.
BACKGROUND
Little is known about genetic predictors that modify the renoprotective effect of renin-angiotensin system (RAS) blockade in IgA nephropathy (IgAN).


METHODS
The present multicenter retrospective observational study examined effect modification between RAS blockade and three RAS-related gene polymorphisms in 237 IgAN patients, including ACE I/D (rs1799752), AT1R A1166C (rs5186) and AGT T704C (rs699).


RESULTS
During 9.9 ± 4.2 years of observation, 63 patients progressed to a 50% increase in serum creatinine level. Only ACE I/D predicted the outcome (ACE DD vs ID/II, hazard ratio 1.86 (95% confidence interval 1.03, 3.33)) and modified the renoprotective effect of RAS blockade (p for interaction between ACE DD and RAS blockade = 0.087). RAS blockade suppressed progression in ACE DD patients but not in ID/II patients (ACE ID/II with RAS blockade as a reference; ID/II without RAS blockade 1.45 (0.72, 2.92); DD without RAS blockade 3.06 (1.39, 6.73); DD with RAS blockade 1.51 (0.54, 4.19)), which was ascertained in a model with the outcome of slope of estimated glomerular filtration rate (p = 0.045 for interaction).


CONCLUSIONS
ACE I/D predicted the IgAN progression and the renoprotective effect of RAS blockade in IgAN patients whereas neither AT1R A1166C nor AGT T704C did.
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Japan.
Junya
J
Teranishi
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Japan.
Ryohei
R
Yamamoto
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Japan.
Yasuyuki
Y
Nagasawa
Department of Kidney Disease and Hypertension, Osaka General Medical Center, Japan.
Tatsuya
T
Shoji
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Japan.
Hirotsugu
H
Iwatani
Clinical Laboratory Medicine, Osaka General Medical Center, Japan.
Noriyuki
N
Okada
Health Care Center, Osaka University, Japan.
Toshiki
T
Moriyama
Division of Nephrology, Department of Internal Medicine, Osaka Rosai Hospital, Japan.
Atsushi
A
Yamauchi
Department of Kidney Disease and Hypertension, Osaka General Medical Center, Japan Department of Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Japan.
Yoshiharu
Y
Tsubakihara
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Japan.
Enyu
E
Imai
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Japan.
Hiromi
H
Rakugi
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Japan isaka@kid.med.osaka-u.ac.jp.
Yoshitaka
Y
Isaka
D000328:Adult; D001706:Biopsy; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D005260:Female; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000187:drug effects
D020011:Protective Agents; D003404:Creatinine
ACE I/D; AGT T704C; AT1R A1166C; Candidate gene approach; PREDICT-IgAN; interaction; renal prognosis