Balkan Journal of Medical Genetics

POLYMORPHISM OF THE ADRB2 rs1042713 GENE IS NOT ASSOCIATED WITH SPONTANEOUS PRETERM BIRTH: ANALYSES IN A SLOVENIAN SAMPLE AND META ANALYSIS
Peterlin A1, Maver A1, Jan Z2, Lovrecic L1, Tul N2, Peterlin B1
*Corresponding Author: Professor Borut Peterlin, Clinical Institute of Medical Genetics, Division of Obstetrics and Gynecology, University Medical Centre Ljubljana, Šlajmerjeva 3, 1000 Ljubljana, Slovenia. Tel/Fax: +386-1-5401-137. E -mail: borut.peterlin@guest.arnes.si
page: 35

INTRODUCTION

Spontaneous preterm birth (SPTB) is the leading cause of neonatal morbidity and mortality worldwide. Approximately 12.0% of all infants are born preterm in the USA; this figure is 6.0-12.0% in the European Union (EU) [1,2], and 7.6% in Slovenia [3]. Infants born preterm can suffer from lifelong morbidities such as developmental delay, lung disease, vision, and hearing deficits, as well as other neurosensory impairments [4,5]. They are also predisposed to hypertension and diabetes in adult life [6]. The etiology of SPTB is multifactorial. In addition to multiple gestations and assisted reproductive technologies, several environmental contributors to SPTB have been proposed, such as an infection [7,8], maternal smoking during pregnancy [9,10], maternal/fetal stress [11,12], adolescence or advanced maternal age [13], cervical dysfunction [14], decidual thrombosis [15], and metabolic enzyme variation [14]. In about 70.0% of SPTB cases no risk factor can be identified, which makes genetic contribution a likely cause to be considered [16]. The role of genetic predisposition to SPTB is based on epidemiological evidence showing that SPTB tends to recur in families. Mothers with previous preterm deliveries have a significantly increased risk of preterm delivery in subsequent pregnancies [17-20]. Spontaneous preterm birth also occurs across generations and sibships [18,21-23]. The heri-tability of SPTB has been estimated to be in the range of 27.0-36.0% [24,25]. Based on their potential role in pathogenesis, as many as 482 genes have already been tested for genetic association with SPTB (HuGENavigator), however, validation of study results remains challenging [26,27]. One of the most frequently investigated candidate genes is the β-2- adrenergic receptor (ADRB2) gene. β-2-Adrenergic receptors, members of the superfamily of G protein-coupled receptors, mediate the catecholamineinduced activation of the adenylate cyclase signaling cascade, a mechanism that plays an important role in smooth muscle relaxation [28]. They are ubiquitously expressed in numerous human tissues, including smooth muscle cells of the trachea, bronchi, vasculature and the uterus. Uterine contractility is modulated by stimulation of ADRB2s with endogenous and exogenous agonists that have a potential to affect cervical tone and resistance to mechanical stretching [29]. Therefore, we hypothesized that genetic variability in the ADRB2 gene modulates uterine contractility and might be consequently associated with SPTB. Several association studies have linked ADRB2 polymorphism rs1042713 and SPTB, but the results were found to be inconsistent [30-33]. Selected polymorphism is a missense polymorphism that results in amino acid change R (Arg)→G(Gly). To address the role of ADRB2 in SPTB, we conducted a two-stage study. First, we designed a casecontrol study, where we investigated whether maternal single nucleotide polymorphism of ADRB2 rs1042713 is associated with the risk of SPTB in the Slovenian population. Second, we carried out a meta analysis to systematically review the association of ADRB2 rs1042713 with SPTB, including the results of this and previously published case-control studies.

Number 26 VOL. 26(1), 2023	Number 25 VOL. 25(2), 2022
Number 25 VOL. 25 (1), 2022	Number 24 VOL. 24(2), 2021
Number 24 VOL. 24(1), 2021	Number 23 VOL. 23(2), 2020
Number 22 VOL. 22(2), 2019	Number 22 VOL. 22(1), 2019
Number 22 VOL. 22, 2019 Supplement	Number 21 VOL. 21(2), 2018
Number 21 VOL. 21 (1), 2018	Number 21 VOL. 21, 2018 Supplement
Number 20 VOL. 20 (2), 2017	Number 20 VOL. 20 (1), 2017
Number 19 VOL. 19 (2), 2016	Number 19 VOL. 19 (1), 2016
Number 18 VOL. 18 (2), 2015	Number 18 VOL. 18 (1), 2015
Number 17 VOL. 17 (2), 2014	Number 17 VOL. 17 (1), 2014
Number 16 VOL. 16 (2), 2013	Number 16 VOL. 16 (1), 2013
Number 15 VOL. 15 (2), 2012	Number 15 VOL. 15, 2012 Supplement
Number 15 Vol. 15 (1), 2012	Number 14 14 - Vol. 14 (2), 2011
Number 14 The 9th Balkan Congress of Medical Genetics	Number 14 14 - Vol. 14 (1), 2011
Number 13 Vol. 13 (2), 2010	Number 13 Vol.13 (1), 2010
Number 12 Vol.12 (2), 2009	Number 12 Vol.12 (1), 2009
Number 11 Vol.11 (2),2008	Number 11 Vol.11 (1),2008
Number 10 Vol.10 (2), 2007	Number 10 10 (1),2007
Number 9 1&2, 2006	Number 9 3&4, 2006
Number 8 1&2, 2005	Number 8 3&4, 2004
Number 7 1&2, 2004	Number 6 3&4, 2003
Number 6 1&2, 2003	Number 5 3&4, 2002
Number 5 1&2, 2002	Number 4 Vol.3 (4), 2000
Number 4 Vol.2 (4), 1999	Number 4 Vol.1 (4), 1998
Number 4 3&4, 2001	Number 4 1&2, 2001
Number 3 Vol.3 (3), 2000	Number 3 Vol.2 (3), 1999
Number 3 Vol.1 (3), 1998	Number 2 Vol.3(2), 2000
Number 2 Vol.1 (2), 1998	Number 2 Vol.2 (2), 1999
Number 1 Vol.3 (1), 2000	Number 1 Vol.2 (1), 1999
Number 1 Vol.1 (1), 1998

About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact