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

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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