Renin-angiotensin polymorphisms and QTc interval prolongation in end-stage renal disease.
BACKGROUND
Polymorphisms of renin-angiotensin system (RAS) genes in patients with end-stage renal disease (ESRD) on chronic hemodialysis may be associated with QTc interval prolongation, leading to fatal arrhythmias. The objective of this study was to determine (1) the prevalence of QTc prolongation in hemodialysis patients, and (2) the association of a prolonged QTc in these patients with RAS polymorphisms [angiotensin-converting enzyme-insertion/deletion (ACE-I/D), angiotensin type 1 receptor-A1166C (AT1R-A1166C), and angiotensinogen-M235T (AGT-M235T)].


METHODS
Twelve-lead electrocardiograms (ECGs), serum electrolytes (sodium, potassium, and calcium), and ACE and angiotensin II levels were obtained 10 to 12 hours after a hemodialysis session in 43 patients with ESRD on chronic hemodialysis [mean age (+/-SD), 55 +/- 14 years]. Using polymerase chain reaction (PCR), the presence of polymorphisms of the ACE-I/D, AT1R-A1166C, and AGT-M235T genes was determined from the buccal cells. A maximum QT interval in patients with sinus rhythm and normal QRS duration was corrected for heart rate using Hodges' formula.


RESULTS
Fifty-eight percent of the patients had QTc interval prolongation (>440 msec). The ACE-DD genotype (P = 0.002) and the C allele of the AT1R-A1166C gene (P = 0.004), but not the AGT-M235T gene, contributed to QTc prolongation.


CONCLUSIONS
Polymorphisms of ACE and AT1R genes additively contribute to QTc prolongation found in a great majority of ESRD patients. Therefore, ESRD patients with both or one of these polymorphisms may be at a higher risk for sudden cardiac death.
Raizada
Veena
V
Department of Internal Medicine, Family and Community Medicine, University of New Mexico, Albuquerque, New Mexico 87131-0001, USA. vraizada@salud.unm.edu
Skipper
Betty
B
Luo
Wentao
W
Garza
Luis
L
Hines
Curt W
CW
Harford
Antonia A
AA
Zager
Philip G
PG
Griffith
Jeffrey
J
Raj
Dominic
D
Spalding
Charles T
CT
D000328:Adult; D000368:Aged; D000808:Angiotensinogen / Q000235:genetics*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D008133:Long QT Syndrome / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D006435:Renal Dialysis; D012084:Renin-Angiotensin System / Q000235:genetics; D012307:Risk Factors
D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A