[Pharmacogenetics of angiotensin system in non diabetic nephropathy].
BACKGROUND
Genetic variability could contribute to the response to pharmacological treatment in patients with nephropathy. In albuminuric diabetic patients the renoprotective effect of angiotensin I-converting enzyme (ACE) inhibition should be lower among homozygotes for the deletion allele (DD) compared to II-homozygotes.


METHODS
A total of 71 non-diabetic chronic nephropathy patients were treated with losartan (n = 37) or amlodipine (n = 34). Blood pressure and proteinuria were determined before and after the treatment, and changes in the mean values were statistically compared. Patients were genotyped for the ACE-I/D, angiotensin I receptor type 1 (AGTR1)-1166 A/C, and angiotensinogen (AGT)-M235T polymorphims, and the reduction of blood pressure and proteinuria between the different genotypes were compared.


RESULTS
The reduction in systolic or diastolic blood pressure was not found to be different between the ACE-I/D or AGT-M/T genotypes in patients treated with losartan or amlodipine. In patients treated with losartan, we found a significantly higher reduction of diastolic blood pressure in AGTR1-AA patients compared to AC patients (p = 0,0024). We did not find differences in proteinuria-reduction between the different genotypes in patients treated with losartan or amlodipine.


CONCLUSIONS
Our data show that the effects of losartan and amlodipine on the absolute mean reduction of blood pressure and proteinuria in non-diabetic nephropathy patients are similar between the different ACE or AGT genotypes. Although based on a small number of patients, the AGTR1-AA genotype was associated with a significantly higher reduction in diastolic blood pressure among losartan-treated patients. Additional studies are necessary to refute or confirm this association.
Coto
E
E
Genética Molecular, Hospital Central de Asturias e Instituto Reina Sofía de Investigación Nefrológica, eliecer.coto@sespa.princast.es
Marín
R
R
Alvarez
V
V
Praga
M
M
Fernández Andrade
C
C
Arias
M
M
Poveda
R
R
Vallés
M
M
Galcerán
J M
JM
Luño
J
J
Rivera
F
F
Campistol
J M
JM
D000328:Adult; D017311:Amlodipine / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002908:Chronic Disease; D003627:Data Interpretation, Statistical; D005260:Female; D005838:Genotype; D005921:Glomerulonephritis / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000235:genetics*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011507:Proteinuria / Q000188:drug therapy / Q000235:genetics
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D017311:Amlodipine; D019808:Losartan