Lack of association of ACE/angiotensinogen genotype with renal function in autosomal dominant polycystic kidney disease.
ACE polymorphisms have recently been shown to associate with worse renal and or cardiovascular outcome, with the D allele widely reported as a risk factor for cardiovascular disease. In autosomal dominant polycystic kidney disease (ADPKD), there are conflicting reports of an association between ACE polymorphisms and disease phenotype. There are no previous reports of any association between angiotensinogen polymorphisms and clinical phenotype in ADPKD. We examined the ACE I/D and angiotensinogen M235T polymorphisms in 176 patients with ADPKD. Patients are categorized into three groups according to the reason for initial investigation. Clinical history and examination findings were recorded at the time of first referral. A cohort of 17 patients had progressive renal impairment observed after 3 or more years of follow-up. Reciprocal creatinine against time was plotted in this group. From the patient population of 176, a total of 33 patients reached end-stage renal failure (ESRF) or a serum creatinine greater than 500 microm/liter. ACE genotype and M235T polymorphism frequencies were compared across groups. Serum creatinine and presence of hypertension and onset of ESRF were taken as outcome variables; age and source of referral were taken as confounding variables. There was no association of any genotype or allele with either creatinine, inverse creatinine, hypertension, or age at end-stage renal failure. These findings do not support the proposition that ACE genotype or angiotensinogen polymorphisms are associated with a worse prognosis in patients with ADPKD.
Saggar-Malik
A K
AK
Medical Genetics Unit, St. George's Hospital Medical School, London, United Kingdom.
Afzal
A R
AR
Swissman
J S
JS
Bland
M
M
Sagnella
G A
GA
Eastwood
J B
JB
MacGregor
G A
GA
Jeffery
S
S
D000808:Angiotensinogen / Q000235:genetics*; D000809:Angiotensins / Q000235:genetics*; D003404:Creatinine / Q000097:blood; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications; D007668:Kidney / Q000503:physiopathology*; D007677:Kidney Function Tests; D007690:Polycystic Kidney Diseases / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic
D000809:Angiotensins; D000808:Angiotensinogen; D003404:Creatinine