High prevalence of ACE DD genotype among north Indian end stage renal disease patients.
BACKGROUND
The Renin-Angiotensin system (RAS) is a key regulator of both blood pressure and kidney functions and their interaction. In such a situation, genetic variability in the genes of different components of RAS is likely to contribute for its heterogeneous association in the renal disease patients. Angiotensin converting enzyme-1 (ACE-1) is an important component of RAS which determines the vasoactive peptide Angiotensin-II.


METHODS
In the present study, we have investigated 127 ESRD patients and 150 normal healthy controls from north India to deduce the association between ACE gene polymorphism and ESRD. The inclusion criteria for patients included a constantly elevated serum creatinine level above normal range (ranging from 3.4 to 15.8) and further the patients were recommended for renal transplantation. A total of 150 normal healthy controls were also genotyped for ACE I/D polymorphism. The criterion of defining control sample as normal was totally based on the absence of any kidney disease determined from the serum creatinin level. Genotyping of ACE I/D were assayed by polymerase chain reaction (PCR) based DNA amplification using specific flanking primers Based on the method described elsewhere.


RESULTS
The difference of DD and II genotypes was found highly significant among the two groups (p = 0.025; OR = 3.524; 95% CI = 1.54-8.07). The combined genotype DD v/s ID+II comparison validated that DD genotype is a high risk genotype for ESRD (p = 0.001; OR = 5.74; 95% CI limit = 3.4-8.5). However, no correlation was obtained for different biochemical parameters of lipid profile and renal function among DD and non DD genotype. Interestingly, approximately 87% of the DD ESRD patients were found hypertensive in comparison to the 65% patients of non DD genotype


CONCLUSIONS
Based on these observations we conclude that ACE DD genotype implicate a strong possible role in the hypertensive state and in renal damage among north Indians. The study will help in predetermining the timing, type and doses of anti-hypertensive therapy for ESRD patients.
Tripathi
Gaurav
G
Department of Medical Genetics, Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow (UP) 226014, India. gaurav_gt1@rediffmail.com
Dharmani
Poonam
P
Khan
Faisal
F
Sharma
R K
RK
Pandirikkal
Vinod
V
Agrawal
Suraksha
S
D000328:Adult; D000804:Angiotensin II / Q000502:physiology; D000959:Antihypertensive Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D007194:India / Q000208:ethnology; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000502:physiology*; D011110:Polymorphism, Genetic / Q000235:genetics; D015995:Prevalence; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology
D000959:Antihypertensive Agents; D000804:Angiotensin II; D003404:Creatinine; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A