Author/Editor		Pleskovič, Aleš; Mankoč Ramuš, Sara; Jenko Pražnikar, Zala; Šantl-Letonja, Marija; Cokan Vujkovac, Andreja; Gazdikova, Katarina; Caprnda, Martin; Gaspar, Ludovit; Kruzliak, Peter; Petrovič, Danijel
Title		Polymorphism rs2073618 of the osteoprotegerin gene as a potential marker of subclinical carotid atherosclerosis in Caucasians with type 2 diabetes mellitus
Type		članek
Vol. and No.		Letnik no. , št. Vol.
Publication year		2017
Volume		str. str.
ISSN		0301-1526 - VASA. Zeitschrift für Gefasskrankheiten
Language		eng
Abstract		Background: The OPG/RANKL/RANK (osteoprotegerin/receptor-activator of nuclear factor kB ligand/receptor-activator of nuclear factor kB) axis has been recently linked to the development of atherosclerosis and plaque destabilization. We have investigated whether polymorphism rs2073618 of the OPG gene is associated with subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). Patients and methods: 595 subjects with T2DM were enrolled in the cross-sectional study. Subclinical markers of carotid atherosclerosis (carotid intima media thickness, plaque thickness, and plaques presence) were assessed with ultrasound at the time of recruitment. Genotyping for rs2073618 (a missense variant located in exon I of the OPG gene) was performed, and OPG serum levels were determined by ELISA. Results: Compared to the GG genotype, the CC genotype of the rs2073618 polymorphism had a significantly increased risk for the presence of carotid plaque (OR = 2.54, 95 % CI = 1.22-5.28, p = 0.01). No statistically significant difference could be detected (p = 0.68) upon comparing median values of serum OPG levels among studied genotype groups in subjects with T2DM. Multivariable linear regression analyses in T2DM subjects demonstrated that GC and CC genotypes (p = 0.03 and p = 0.003), together with statin therapy (p = 0.009), were independent predictors of the number of carotid segments with plaques. Conclusions: Despite the fact that OPG rs2073618 genotypes failed to predict the serum OPG levels as there was no statistical difference among compared genotypes, our results demonstrate that the rs2073618 polymorphism could be a possible genetic marker for the prediction of increased risk for carotid plaque burden as a measure of advanced subclinical atherosclerosis in T2DM subjects.
Keywords		subclinical carotid atherosclerosis genetic polymorphism type 2 diabetes mellitus subklinična karotidna ateroskleroza genetski polimorfizem diabetes mellitus tipa 2