Abstract: Background: The rennin angiotensin system (RAS) is central to the pathogenesis of hypertension,
cardiovascular disease and kidney disease. Angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor
(AT1R) are two of the main components of the RAS. The genetic polymorphisms of these key components provide
a basis for studying the relationship between genetic variants and the development of vascular or renal damage in
individual subject. This work aimed to study the distribution of I/D polymorphism of ACE and AT1R
polymorphism in chronic kidney disease (CKD) patients and their association with other clinical and laboratory
variables in these patients. Methods: Gene polymorphisms were studied in 64 CKD patients (40 on hemodialysis
"HD" & 24 on conservative treatment "CT") and 20 healthy controls using PCR amplification for ACE gene and
PCR-RFLP technique for AT1R gene. Serum ACE activity, kidney functions and lipid profile were measured in all
the studied groups. Results: Higher frequency of D allele of ACE gene was observed in CKD (both on HD or CT)
patients than healthy controls (p<0.0001 & p<0.01 respectively) with higher distribution in HD patients than those
on CT (p <0.05). HD group had higher frequency of DD genotype compared to controls (p<0.01). The I allele and II
genotype showed higher distribution in healthy controls than CKD patients (HD and CT) (p<0.0001 and p<0.01
respectively). Patients on CT had higher frequency of I allele and II genotype when compared to those on HD
(p<0.05 for both). The C allele of AT1R showed higher frequency in HD group in comparison with controls
(p<0.05) but the A allele showed lower frequency in the HD patients compared to controls (p<0.05). No significant
difference was found in comparing the frequency of AA, AC or CC genotypes between the studied groups. The
number of hypertensive patients was higher in patients carrying DD genotype than those carrying II and ID genotype
(p<0.05). Estimated glomerular filtration rate (e-GFR) was lower in AC and CC genotype carriers than AA genotype
carriers (p<0.05). Study of the frequency of combined genotypes revealed that ACE-ID+AT1R-AA is the most
frequent genotype combination in CKD patients (40.6%) and ACE-II+AT1R-AA is the most frequent combination
in controls (60%). Conclusion: The D allele of ACE gene and the C allele of AT1R are important genetic
determinants in CKD. They are more frequent in HD patients than those on CT. Patients carrying these alleles have
higher ACE activity and more prone to hypertension. They also have more decline in kidney function as evidenced
by lower values of e-GFR. They can be considered as risk alleles