Nephrol Dial Transplant (2006) 21: 979–983
doi:10.1093/ndt/gfk012
Advance Access publication 29 December 2005
Original Article
Genetic polymorphisms of the renin-angiotensin system
in end-stage renal disease
Monika Buraczynska1,2,, Piotr Ksiazek1,, Andrzej Drop3, Wojciech Zaluska2,
Danuta Spasiewicz1 and Andrzej Ksiazek2
1
Laboratory for Molecular Diagnostics of Multifactorial Diseases, 2Department of Nephrology and
3
Department of Radiology, University Medical School, Lublin, Poland
*MB and PK contributed equally to this paper.
Abstract
Background. End-stage renal disease (ESRD) is a
complex phenotype resulting from underlying kidney
diseases of different etiologies as well as from environ-
mental and genetic factors. The responsible genes
influencing the development and rate of progression
to ESRD have yet to be defined. We examined an
association of the three renin-angiotensin system
(RAS) gene polymorphisms with renal disease and
progression to ESRD in dialyzed patients.
Methods. Genotyping was performed in 745 ESRD
patients and 520 control subjects for the angiotensin-
converting enzyme (ACE) I/D, angiotensinogen (AGT)
M235T and angiotensin II type 1 receptor (AT1R)
A1166C gene polymorphisms using polymerase chain
reaction and gel analysis.
Results. Allele and genotype frequencies of the ACE
polymorphism did not differ significantly between
ESRD patients and controls. The patient group
showed an increased frequency of the T allele of the
AGT polymorphism (P ¼ 0.02) and the C allele and
CC genotype of the AT1R polymorphism (P<0.01).
There was an association of the AT1R gene poly-
morphism with the progression of renal disease to
end-stage failure. The time from diagnosis to the onset
of ESRD was significantly shorter in patients carrying
the C allele than in subjects with the homozygous
AA genotype (4.7 years vs 12.6 years, P<0.001). The
observed effect was not associated with hypertension in
studied subjects.
Conclusion. The results of our study demonstrate the
association between the AT1R A/C polymorphism and
renal disease progression. The CC/AC genotype of this
polymorphism might serve as a predictor for early
Correspondence and offprint requests to: Monika Buraczynska,
Laboratory for Molecular Diagnostics of Multifactorial Diseases,
Department of Nephrology, University Medical School,
Dr K. Jaczewskiego 8, 20-954 Lublin, Poland.
Email: monika.buraczynska@am.lublin.pl
ß The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
For Permissions, please email: journals.permissions@oxfordjournals.org
Downloaded from https://academic.oup.com/ndt/article/21/4/979/1932471 by guest on 09 April 2022
ESRD and might be useful in planning therapeutic
strategies for individual patients.
Keywords: angiotensin-converting enzyme;
angiotensinogen; angiotensin II type 1 receptor;
DNA polymorphisms; end-stage renal disease
Introduction
The renin-angiotensin system (RAS) has been strongly
implicated in the pathogenesis of essential hyper-
tension, cardiovascular disease and progressive renal
disease [1–3]. RAS plays a central role in the regulation
of blood pressure, sodium metabolism and renal hae-
modynamics, with its actions mediated primarily by
angiotensin II. Angiotensin II is a powerful vasocons-
trictor and mediator of cellular proliferation and extra-
cellular matrix protein synthesis and accumulation.
Intrarenal effects of the RA system include changes in
renal haemodynamics, such as increase in intraglomer-
ular pressure as well as direct stimulation of mesangial
cell proliferation and matrix production [4,5].
Association studies based on the comparison of
genotype and allele distribution in cases and controls
are considered a useful approach in studying the role of
candidate genes in the development and progression
of multifactorial diseases. Among the candidate genes
of the RAS, the angiotensin-converting enzyme (ACE),
angiotensinogen (AGT) and angiotensin II type 1
receptor (AT1R) genes seem to be particularly biologi-
cally and clinically relevant to renal disease. The genetic
polymorphisms of these key components of RAS
provide a basis for studying the relationship between
genetic variants and the development of vascular
and/or renal damage in individual subjects [6–8].
ACE gene has a frequent insertion-deletion (I/D)
polymorphism characterized by the presence or absence
980
of a 278 bp Alu repetitive sequence in intron 16. This
polymorphism is associated with circulating ACE levels
[6,9].
Several polymorphisms were identified in the AGT
gene which was linked to essential hypertension.
Of those, M235T polymorphism (methionine
substituted by threonine) was extensively studied in
cardiovascular and renal diseases [3].
AT1R polymorphism A1166C is due to a substitu-
tion of cytosine for adenine at the position 1166 in 30
untranslated region. It has been considered a risk factor
for hypertension and cardiovascular disease [5].
In the present study we examined the association
of the ACE, AGT and AT1R gene polymorphisms
with the development and progression of end-stage
renal disease (ESRD) in a fairly large population of
dialysis patients.
Subjects and methods
Patients and controls
The study population consisted of 745 unrelated adult
individuals on maintenance dialysis (687 haemodialysis and
58 peritoneal dialysis), recruited from ten dialysis centers.
All patients were Caucasians of Polish origin. ESRD resulted
from chronic glomerulonephritis (n ¼ 246) and interstitial
nephritis (n ¼ 121) (both confirmed by renal biopsy in
majority of patients) as well as from diabetic nephropathy
(n ¼ 141), polycystic kidney disease (n ¼ 69), hypertensive
nephropathy (n ¼ 53), obstructive nephropathy (n ¼ 33) and
other causes. In about 4% of patients the renal disorder could
not be diagnosed adequately.
From the study group, 583 patients (78.2%) were
hypertensive and on antihypertensive medication at the
start of dialysis. Hypertension was defined as a systolic
blood pressure >140 mmHg and a diastolic blood pressure
>90 mmHg. Positive family history in first degree relatives
was reported by 163 patients (22%). Creatinine, urea,
electrolytes, total cholesterol and other standard chemistry
evaluations were performed in serum, at the onset of dialysis
therapy, according to routine methods. The time interval
from the first diagnosis of renal disease to ESRD was assessed
by clinicians who did not know the genotype status of the
patients.
Healthy control subjects (n ¼ 520), with no clinical signs
of vascular or renal disease and no family history of renal
disease, were recruited among hospital staff and blood bank
donors. An informed consent for genetic studies was obtained
from all subjects. The protocol of the study was read and
approved by the ethics committee of the University Medical
School in Lublin.
Determination of genotypes
Genomic DNA was isolated from all subjects from peripheral
blood leukocytes by the standard method.
Angiotensin I-converting enzyme I/D genotype was
determined using standard protocol [9]. Because of the
preferential amplification of the D allele, each DD genotype
was confirmed by using insertion-specific primers [10].
Amplification products had the size of 490 bp for the insertion
M. Buraczynska et al.
allele and 190 bp for the deletion allele. With the use of
insertion-specific primers, the product of 335 bp was obtained.
Detection of the AGT gene M235T polymorphism was
performed by restriction typing of polymerase chain
reaction (PCR) product. The following primers were used:
forward: 50 -CCGTTTGTGCAGGGCCTGGCTCTCT-30 and
reverse: 50 -CAGGGTGCTGTCCACACTGGACCCC-30 .
Genomic DNA (300 ng) was amplified in a final volume of
50 ml, containing 10 mM TRIS pH 8.3, 50 mM KCl, 1.5 mM
MgCl2, 200 mM each dNTP, 1 mM of each primer and 2 U Taq
polymerase (all reagents from MBI Fermentas, St. Leon-Rot,
Germany). The initial denaturation at 95
C was followed
by 35 cycles of denaturation at 94
C, annealing at 65
C and
elongation at 72
C, 1 min each. Final extension was at 72
C
for 7 min. The PCR products were digested with PsyI
restriction enzyme (MBI Fermentas, St. Leon-Rot,
Downloaded from https://academic.oup.com/ndt/article/21/4/979/1932471 by guest on 09 April 2022
Germany) and DNA fragments were separated by electro-
phoresis in 2% agarose gel stained with ethidium bromide.
The M allele was detected as a band of 165 bp, whereas the
mutated T allele showed two fragments, 141 bp and 24 bp.
The A1166C variant of the AT1R gene was identified
with primers: forward: 50 -GCAGCACTTCACTACCAAAT
GGGC-30 and reverse: 50 -CAGGACAAAAGCAGGCTA
GGGAGA-30 . The reaction conditions were the same as
for the AGT polymorphism, except for the annealing step
which was at 55
C. The PCR products were digested with
BsuRI restriction enzyme (MBI Fermentas, St. Leon-Rot,
Germany). In the presence of cytosine there is a restriction site
for this enzyme, resulting in a fragment 231 bp (C allele).
Undigested 255 bp fragment indicates the presence of the
A allele.
Statistical analysis
Statistical calculations were performed using SPSS for
Windows 5.0 (SPSS Inc., Chicago, IL). Hardy–Weinberg
equilibrium was tested with the 2 test. Genotype distribution
and allele frequencies were compared between groups using a
2 test of independence and z statistics. Odds ratios (OR) with
95% confidence intervals (CI) were estimated for the effects of
high risk alleles. Student’s t-test was used to compare mean
times to ESRD between genotypes. Values of P (two-tailed)
<0.05 were considered statistically significant.
Results
We genotyped 745 patients undergoing maintenance
dialysis and 520 healthy controls for the ACE, AGT
and AT1R gene polymorphisms. The clinical charac-
teristics of both groups are presented in Table 1. The
baseline serum creatinine levels and blood pressure
values did not differ between genotypes.
The genotype frequencies in each group satisfied the
Hardy–Weinberg equilibrium.
The distribution of genotype and allele frequencies
were compared between patients and controls (Table 2).
Analysing the entire patient group, no significant
difference was observed in the genotype distribution
and allele frequencies for the ACE gene polymorphism.
The carriers of the T allele of the AGT polymorphism
were more frequent in the patient group compared to
RAS polymorphisms in end-stage renal disease 981
Table 1. Clinical characteristics of studied subjects Table 3. Allele frequencies in dialysis patients with different
primary renal diseases
Characteristic Dialysis patients Controls
(n ¼ 745) (n ¼ 520) Primary disease ACE AGT AT1R

n I D M T A C
Age at study (years) 51.1±11.6 48.3±9.6
Sex (M/F) 415/330 294/226
Dialysis duration (years) 4.5±3.3 NA All patients 745 0.46 0.54 0.49 0.51 0.68 0.32
Time to ESRD (years) 9.8±5.1 NA Glomerulonephritis 246 0.44 0.56 0.47 0.53 0.66 0.34
Total cholesterol (mg/dl) 189.2±41 171±48 Diabetic nephropathy 141 0.44 0.56 0.51 0.49 0.67 0.33
Serum creatinine (mg/dl) 8.9±2.32 ND Interstitial nephritis 121 0.45 0.55 0.44 0.56 0.69 0.31
Hypertension (%) 583 (78.2) 0
Diabetes mellitus (%) 141 (19) 0
Family history of renal disease (%) 163 (22) 0
GFR 9.36±3.59 ND

Values are presented as mean±SD. NA: not applicable. ND: not

Downloaded from https://academic.oup.com/ndt/article/21/4/979/1932471 by guest on 09 April 2022

determined.

Table 2. Distribution of alleles and genotypes in dialysis patients

and controls

Polymorphism Dialysis patients (n ¼ 745) Controls (n ¼ 520)

ACE
alleles I/D 0.46/0.54 0.47/0.53
genotypes: II 171 (23) 112 (21.5)
ID 346 (46.4) 268 (51.5)
DD 228 (30.6) 140 (27)
For D allele carriers OR ¼ 0.92 (95% CI: 0.70–1.20)
Patients vs controls 2 ¼ 0.28, P ¼ 0.59 Fig. 1. Progression to ESRD in dialyzed patients.

AGT
alleles M/T 0.49/0.51 0.54/0.46
genotypes: MM 190 (25.5) 163 (31)
MT 354 (47.5) 238 (46)
significant differences were observed compared to the
TT 201 (27) 119 (23) whole patient group.
For T allele carriers OR ¼ 1.33 (95% CI: 1.04–1.70) Genetic polymorphisms of the ACE, AGT and
Patients vs controls 2 ¼ 4.91, P ¼ 0.02 AT1R genes were analysed for their association with
AT1R the rate of progression to ESRD. The results are shown
alleles A/C 0.68/0.32 0.80/0.20 in Figure 1. Progression of renal disease to the end-
genotypes: AA 346 (46.5) 322 (62) stage failure in our patient group was influenced by the
AC 322 (43.2) 182 (35) AT1R polymorphism. We pooled patients homo- and
CC 77 (10.3) 16 (3.0)
For C allele carriers OR ¼ 1.87 (95% CI: 1.49–2.35) heterozygous for the C allele for comparison with the
2
Patients vs controls  ¼ 28.83, P<0.0001 AA homozygotes. The time from diagnosis to the onset
of ESRD was significantly shorter for patients carrying
ACE, angiotensin-converting enzyme; AGT, angiotensinogen; the C allele than for subjects with the homozygous AA
AT1R, angiotensin II type 1 receptor; Percentages are shown in
parentheses; NS, not significant. P-values given where significant.
genotype (4.7 vs 12.6 years, P<0.001). When progres-
sion to ESRD was compared between the AA and
AC/CC genotypes in dialysis patients with different
primary renal diseases, the highest rate of progression
controls (P ¼ 0.02). The dialysis patient group also was observed in interstitial nephritis patients with
showed an increased frequency of the C allele and the the C allele (4.1 vs 13.3 years for AC þ CC subjects).
homozygous CC genotype of the AT1R polymorphism, The differences between studied primary diseases were
compared to controls (0.32 vs 0.20 and 10.3 vs 3%, not statistically significant.
respectively), OR ¼ 1.87 (95% CI: 1.49 to 2.35). The No significant differences were found when hyper-
frequency of combined AC and CC genotypes was also tensive and normotensive patients with AC þ CC vs AA
higher in the patient group (53.5 vs 38%, P<0.05). genotypes were compared (data not shown).
Dialyzed patients with hypertension and those without Some interesting results were obtained when the
it showed very similar frequencies of genotypes and patient population was divided into late (>50 years
alleles of studied polymorphisms (P ¼ 0.08 for ACE, of age) and early disease onset subgroups (281
0.12 for AGT and 0.31 for AT1R). and 464 individuals, respectively). The homozygous
Allele frequencies of the examined polymorphisms in TT genotype of the AGT gene polymorphism was
the subgroups of patients with most frequent primary more frequent in the late onset subgroup (38 vs 12%,
renal diseases are presented in Table 3. No statistically P<0.001). Mean time to ESRD in this subgroup
982
was 3.3 vs 8.7 years for the early onset subgroup
(P<0.01).
Discussion
Renal disease progression results from the interaction
of multiple environmental and genetic factors. Several
studies have shown a relationship between genetic
variants of the renin-angiotensin system genes and
renal diseases as well as the rate of progression of renal
damage (reviewed in [3]). There are also studies with
negative results concerning these polymorphisms.
Therefore, including large numbers of patients from
the same population might benefit evaluation of these
relationships and add to our knowledge.
We examined the association between the ACE,
AGT and AT1R gene polymorphisms and ESRD in
dialyzed patients. There are only a few papers published
concerning the relationship of these polymorphisms
with the rate of progression to ESRD in patients with
chronic renal failure resulting from different diseases.
The I/D polymorphism of the ACE gene was studied
frequently in cardiovascular and renal diseases. Several
reports link this polymorphism to the development
and progression of chronic renal diseases of different
etiologies [11–14]. Some of these studies, however,
involve rather small numbers of patients (n<80). As the
association studies are critically dependent on sample
size, we included a large group of dialyzed patients
in our study. In this group ACE allele frequencies
were similar to those described by others for the Polish
population. Neither the distribution of ACE genotypes
nor the D allele frequency in the entire patient group
showed any difference from those in the control group.
After dividing a patient population according to
underlying renal disease, we still did not observe
any differences. This lack of association between the
ACE I/D polymorphism and renal failure in our study
is in agreement with some reported data, either for the
entire ESRD population [15] or the particular primary
renal disease [16–18].
Several reports investigated the relationship between
the AGT gene M235T polymorphism and development
and progression of renal failure in patients with
different primary renal diseases. Some reported an
association of the T allele of this polymorphism with
development of chronic renal disease and renal failure
[11,14,19]. There are also contradictory reports,
from different populations, that failed to find such
association [18,21]. In our study the TT genotype was
more frequent in the patient group compared to healthy
individuals, but the strong association of the TT
genotype of the M235T polymorphism with develop-
ment of renal failure was observed only in patients
with onset of renal disease after 50 years of age. At
present this association is difficult to explain and will
be a subject of further investigation. The AGT 235T
allele is in a linkage disequilibrium with the AGT-6A
allele of the promoter region polymorphism which was
found to increase the level of transcription of AGT [20].
M. Buraczynska et al.
In a separate study, we genotyped 710 patients from our
ESRD group and 490 controls with the AGT G(-6)A
polymorphism. The frequency of the A allele was
higher in dialyzed patients than the controls (P ¼ 0.04;
data not shown). The functional role of the M235T
polymorphism, alone or in conjunction with the G(-6)A
polymorphism cannot be excluded.
The interesting finding of our study was the associa-
tion of the AT1R genotype with the development of
renal disease and progression to end-stage renal failure.
This confirms our previous results [22] with 430 ESRD
patients investigated (206 of which, genotyped for all
three polymorphisms, were used in the present inves-
tigation). We observed a significant difference in the
frequency of the C allele and CC homozygotes between
Downloaded from https://academic.oup.com/ndt/article/21/4/979/1932471 by guest on 09 April 2022
patients and controls. Due to a small number of
patients with the CC genotype, AC and CC genotypes
were pooled for the renal deterioration analysis.
Patients carrying the C allele showed more rapid
deterioration of renal function than those with the
AA genotype. This, to our knowledge, was earlier
reported only by us for a dialyzed patient population
[22]. In one study, time to ESRD in female patients with
diabetic nephropathy who had AC/CC genotype
was significantly shorter than in those with the AA
genotype [21]. The comparison between hypertensive
and normotensive patients indicates that the associa-
tion of the C allele with renal failure and faster
progression to ESRD is independent of hypertension
(data not shown).
We are not sure at this point whether the association
of the C allele with renal failure progression is
dependent on underlying kidney disease. In our
previous study [22] the strongest effect was observed
in interstitial nephritis. In the present study the highest
rate of progression to ESRD was also observed in
interstitial nephritis patients with the C allele, but
compared to other underlying diseases the differences
were not statistically significant. Although we studied
a large group of patients, this number is probably
still inadequate to assess the role of the C allele in
individual disease subgroups.
The risk of renal failure associated with the AT1R C
allele seems to be more apparent in dialyzed patients
with a positive family history. However, an interactive
effect of several factors may lead to an underestimation
or an overestimation of the role of any studied
polymorphism in determining the phenotype.
The mechanism by which the AT1R A/C poly-
morphism affects the development of renal disease and
its progression to ESRD remains to be elucidated. It is
possible that predisposition to renal disease is related to
genetic variability in the sensitivity of target tissues
to angiotensin II whose actions are mediated by the
AT1R receptor. The studied polymorphism is located
in the 30 untranslated region of the gene and is
apparently a nonfunctional mutation [23]. It may be
linked, however, to an unidentified functional mutation
in the AT1R gene or in another closely linked gene
possibly located in regulatory regions, involved in the
development and progression of renal damage.
RAS polymorphisms in end-stage renal disease
There are several reports concerning an interaction
between RAS gene polymorphisms, affecting the
development and progression of cardiovascular and
renal disease. Such interactions were observed between
the ACE I/D and AGT M235T polymorphisms [14,24],
and between ACE I/D and AT1R polymorphisms
[1,25]. The relation between AT1R genotype and the
progression of ESRD was assessed separately in groups
of subjects with different ACE and AGT genotypes. No
unfavorable combination of genotypes was found (data
not shown).
In conclusion, the present study has failed to confirm
any effect of the ACE gene I/D polymorphism on the
progression of renal failure in the entire group of
dialysis patients, although a fairly large group of ESRD
patients was genotyped. We demonstrate the presence
of an association between the AGT gene polymorphism
(the strongest in patients with late onset of renal
disease) and the AT1R A/C polymorphism and renal
disease progression. Our results suggest that in patients
with chronic renal disease, if confirmed in prospective
studies analysing GFR decline over time, the CC/AC
genotype might serve as a predictor of an early ESRD.
This implies that genotyping for the AT1R gene
polymorphism could in the future become an important
part of the clinical process of renal risk identification.
Acknowledgements. This study was supported by the University
Medical School grant DS 233/02.
Conflict of interest statement. None declared.
References
1. Alvarez R, Requero JR, Batalla A et al. Angiotensin-converting
enzyme and angiotensin II receptor 1 polymorphisms: associa-
tion with early coronary disease. Cardiovasc Res 1998; 40:
375–379.
2. Pontremoli R, Ravera M, Viazzi F et al. Genetic polymorphism
of the renin-angiotensin system and organ damage in essential
hypertension. Kidney Int 2000; 57: 561–569.
3. Schmidt S, Ritz E. Genetics of the renin-angiotensin system and
renal disease: a progress report. Curr Opin Nephrol Hypertens
1997; 6: 146–151.
4. Burns KD. Angiotensin II and its receptors in the diabetic
kidney. Am J Kidney Dis 2000; 36: 449–467.
5. Kim S, Iwao W. Molecular and cellular mechanisms of
angiotensin II-mediated cardiovascular and renal diseases.
Pharmacol Rev 2000; 52: 11–34.
6. Crisan D, Carr J. Angiotensin I-converting enzyme.
Genotype and disease associations. J Molec Diagnostics 2000;
2: 105–114.
7. Ortiz MA, De Prado A, Donate T et al. Angiotensin-converting
enzyme polymorphism gene and evolution of nephropathy to
end-stage renal disease. Nephrology 2003; 8: 171–176.
8. Miller JA, Scholey JW. The impact of renin-angiotensin system
polymorphisms on physiological and pathophysiological
processes in humans. Curr Opin Nephrol Hypertens 2004; 13:
101–106.
983
9. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P,
Soubrier F. An insertion/deletion polymorphism in the
angiotensin I-converting enzyme gene accounting for half the
variance of serum enzyme levels. J Clin Invest 1990; 86:
1343–1346.
10. Lindpainter K, Pfeffer MA, Kreutz R et al. A prospective
evaluation of an angiotensin-converting enzyme gene poly-
morphism and the risk of ischemic heart disease. N Engl J Med
1995; 322: 706–711.
11. Gumprecht J, Zychma MJ, Grzeszczak W, Zukowska-
Szczechowska E, End-Stage Renal Disease Study Group.
Angiotensin I-converting enzyme gene insertion/deletion and
angiotensinogen M235T polymorphisms: risk of chronic renal
failure. Kidney Int 2000; 58: 513–519.
12. Mallamaci F, Zuccala A, Zoccali C et al. The deletion
polymorphism of the angiotensin-converting enzyme is asso-
ciated with nephroangiosclerosis. Am J Hypertens 2000; 13:
Downloaded from https://academic.oup.com/ndt/article/21/4/979/1932471 by guest on 09 April 2022
433–437.
13. Samuelsson O, Attman PO, Larsson R et al. Angiotensin I-
converting enzyme gene polymorphism in non-diabetic renal
disease. Nephrol Dial Transplant 2000; 5: 81–86.
14. Lovati E, Richard A, Frey BM, Frey FJ, Ferrari P. Genetic
polymorphisms of the renin-angiotensin-aldosterone system in
end-stage renal disease. Kidney Int 2001; 60: 46–54.
15. Schmidt A, Kiener HP, Barnas U et al. Angiotensin-converting
enzyme polymorphism in patients with terminal renal failure.
J Am Soc Nephrol 1996; 7: 314–317.
16. Schmidt S, Schone N, Ritz E, The Diabetic Nephropathy
Study Group. Association of ACE gene polymorphism and
diabetic nephropathy? Kidney Int 1995; 47: 1176–1181.
17. Grzeszczak W, Zychma NJ, Lacka B, Zukowska-Szczechowska
E. Angiotensin I-converting enzyme gene polymorphisms:
relationship to nephropathy in patients with non-insulin
dependent diabetes mellitus. J Am Soc Nephrol 1998; 9:
1664–1669.
18. Frimat L, Philippe C, Maghakian MN. Polymorphism of
angiotensin converting enzyme, angiotensinogen, and angio-
tensin II type 1 receptor genes and end-stage renal failure in
IgA nephropathy: IGARAS – A study of 274 men. J Am Soc
Nephrol 2000; 11: 2062–2067.
19. Rogus JJ, Moczulski D, Freire MB, Yang Y, Warram JH,
Krolewski AS. Diabetic nephropathy is associated with AGT
polymorphism T235T: results of a family-based study.
Hypertension 1998; 31: 627–631.
20. Inoue I, Nakajima T, Williams CS et al. A nucleotide
substitution in the promoter of human angiotensinogen is
associated with essential hypertension and affects basal
transcription in vitro. J Clin Invest 1997; 99: 1786–1797.
21. Tomino Y, Makita Y, Shike T et al. Relationship between
polymorphism in the angiotensinogen, angiotensin-converting
enzyme or angiotensin II receptor and renal progression in
Japanese NIDDM patients. Nephron 1999; 82: 139–144.
22. Buraczynska M, Ksiazek P, Zaluska W, Spasiewicz D,
Nowicka T, Ksiazek A. Angiotensin II type 1 receptor gene
polymorphism in end-stage renal disease. Nephron 2002; 92:
51–55.
23. Bonnardeaux A, Davies E, Jeunemaitre X et al. Angiotensin II
type 1 receptor gene polymorphisms in human essential
hypertension. Hypertension 1994; 24: 63–69.
24. Bantis C, Ivens K, Kreusser W et al. Influece of genetic
polymorphisms of the renin-angiotensin system on IgA
nephropathy. Am J Nephrol 2004; 24: 258–267.
25. Ye S, Dhillon S, Seear R et al. Epistatic interaction between
variations in the angiotensin I converting enzyme and
angiotensin II type 1 receptor genes in relation to extent of
coronary atherosclerosis. Heart 2003; 89: 1195–1199.
Received for publication: 25.3.05
Accepted in revised form: 29.11.05