POLYMORPHISM OF ANGIOTENSIN-CONVERTING
ENZYME (rs4340) AND DIABETIC NEPHROPATHY IN
CAUCASIANS WITH TYPE 2 DIABETES MELLITUS Šeruga M, Makuc J,, Završnik M, Cilenšek I, Ekart R, Petrovič D M. Šeruga and J. Makuc contributed equally to this study. *Corresponding Author: Professor Dr. Daniel Petrovič, M.D., Ph.D., Institute of Histology and Embryology, Faculty of
Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia. Tel: +386-1-543-7360. Fax: +386-1-543-7361.
E-mail: daniel.petrovic@mf.uni-lj.si page: 29
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DISCUSSION
In our cross-sectional study we found no association
between rs4340 of the ACE gene and DN in Caucasians
with T2DM. Conflicting reports have been made in different
populations on the association between the I/D polymorphism
in the ACE gene (rs4340) and DN. Our findings
are in accordance with the study in French subjects with
T2DM, but they differ from most studies performed in
Chinese, Japanese and Indian populations, as well as in
two meta-analyses in Asian and Arab patients with T2DM
[13,19,20,23,25-29].
Wide inter-ethnic differences have been reported for
allele/genotype frequencies of the I/D polymorphism of
the ACE gene (rs4340), and these differences have been
assumed to be responsible for the contradictory results
among association studies in subjects with DN [13,19,
20,23-26]. An association between rs4340 and DN was
demonstrated in Asian populations (Japan, South India)
[20,23] but not in Iran [31] and Malaysia [32]. A metaanalysis
has demonstrated that the ACE I/D gene polymorphism
affected the development of DN, i.e., that the D
allele was a risk factor for DN, and I allele was a protective
factor against DN in T2DM in an Asian population [26,33].
Another meta-analysis [27] reported that ACE I/D gene
polymorphism (rs4340) was associated with T2DM in an
Arab population. Moreover, the D/D genotype (rs4340)
was reported to be an independent risk factor for renal end
points in Chinese patients with T2DM [24]. Wang et al.
[34] have recently demonstrated an association between
the D allele (rs4340) and glomerular filtration impairment
in Chinese patients with T2DM.
There were only a few reports in Caucasians [25,28,
29]. In a large case-control study, which enrolled patients
in France, Finland and Denmark, it was shown that the
rs4340 was associated with DN in subjects with type 1
diabetes mellitus (T1DM) [29]. Additionally, the D allele
(rs4340) was reported to be an independent risk factor
for both the onset and the progression of DN in T1DM
patients [30]. Moreover, Yu et al. [25] reported that the
DD genotype (rs4340) was associated with the end-stage
renal disease in DN patients with T2DM. Contrary to the
association between rs4340 and DN in T1DM, Hadjadj et
al. [28] were not able to demonstrate an association between
the rs4340 and DN in French subjects with T2DM,
whereas so far, there have been no reports of rs4341 and
DN in Caucasians.
A limitation of our study was the use of cross-sectional
data in the analyses, restricting the possibility of
causal inferences from our data. Another limitation of
the study was the sample size. The strength of our crosssectional
study was a rather large community-based sample of Caucasians with T2DM, and the detailed phenotypic
characterization of the subjects with DN. In conclusion,
rs4340 of the ACE gene was not demonstrated to be a potential
genetic marker for DN in Caucasians with T2DM.
Declaration of Interest. The authors report no conflicts
of interest. The authors alone are responsible for the
content and writing of this article.
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