Association Between of insertion/deletion (I/D) polymorphism of the ACE Gene and kidney transplant outcome


Leila Ghotbi1 , Mohsen Nafar2, Seyed Mohammad Hossein Ghaderian2 , Andia Taleb 1, Samaneh Ghayem Amani1 , Mohammad Samzadeh 1,2, Mahdieh Imani1, Mahdi Afshari3, Mandana Hasanzad1. 1. Medical Genomics Research Center, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran. 2. Urology and Nephrology Research Center (UNRC), Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Department of Community Medicine, Zabol University of Medical Sciences, Zabol, Iran.


Mandana Hasanzad -

 Background:Genetic variations of the renin–angiotensin system (RAS) genes can be among the potential factors that may affect on kidney transplant outcome. But this association is controversial. The aim of this study was to analyze any association between polymorphic variants of the angiotensin-converting enzyme (insertion/deletion) and kidney transplant outcome.

Materials and Methods: Totally, 169 patients undergoing kidney transplantation due to renal disease were recruited in the study. Mean (SD) age of the participants was 43.90(13.08). Among participants 39(23.08%) cases had history of transplant rejection. The patients were classified into two groups according to Acute Rejection (AR) episodes. TheI/D polymorphisms in ACE gene were determined by RFLP.

Results: Patients with rejected transplantation, received kidney from dead donors more than those who had no history of rejection (46.15 vs 38.46, p=0.4). Mean duration of dialysis before transplantation (21.21+- 37.08 vs 15.82+-19.02, p=0.2) and mean BUN (35.18±19.10 vs 30.74±13.76) among these patients were more than those among non-rejected patients Although, none of the above differences were not statistically significant. They had also hypercreatinemia more than controls (92.31% vs zero) which was statistically significant (p<0.0001). On the other hand, history of hypertension (100% vs 90.91%, p=0.07) and diabetes mellitus (16.15 vs 10.26, p=0.3) were more in patients whose transplantation was not rejected compared to cases. Although patients with transplant rejection had more frequency of having DD genotype, this difference was not statistically significant (50% vs 51.16%, p=0.8). Crude odds ratio between ID genotype and risk of rejection was 2.40 (p=0.4) and crude odds ratio between DD genotype and rejection was 2.07 (p=0.5). It means that these two genotypes increased the odds of transplant rejection more than two folds as compared to II genotype; however, these associations were not statistically significant. Multivariate logistic regression models showed that having adjusted for age and sex, these associations were not changed (OR=2.6, p=0.4 and OR=2.22, p=0.5 respectively, although still it was not statistically significant. On the other hand, these associations were markedly reversed when controlling for age, sex, serum BUN, hemoglobin, blood pressure, serum creatinine and duration of dialysis before transplantation (OR=0.70, p=0.8 and OR=0.66, p=0.7 respectively), indicated a protective effect of DD and ID in developing transplant rejection from different pathways. It should be mentioned that none of the above associations were statistically significant. Therefore, there is not any effect of this genotype in transplant rejection. Frequency of D allele among patients with history of rejected transplantation was slightly more than that of patients without but the difference was not statistically significant (73.08% vs 71.51%, p=0.8). Regression models showed that although D allele increased the odds of rejection about eight percent, this allele could not be considered as a risk factor for transplant rejection, because this association was not statistically significant (OR=1.08, p=0.8).


Conclusions:Finally, it may be concluded that sensitivity of DD genotype in diagnosis the potential transplant rejection is very low. It means that this genotype is only detected in half of patients with rejection. Specificity is low too indicated that DD genotype would be negative only in half of the normal transplants. . So these polymorphisms cannot be considered as risk factors of acute allograft rejection in Iranian renal transplantation recipients.