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

DISCUSSION

In the case-control association study in the Slovenian population and meta-analysis of previous studies, we did not find any evidence of an association between SPTB and ADRB2 rs1042713. In the Slovenian population case-control association study, we also did not find any difference in ADRB2 rs1042713 polymorphism allele and genotype distribution between SPTB and controls. The arginine (A allele) at rs1042713 was reported to be associated with reduced downregulation of gene expression and reduced desensitization of ADRB2 leading to a change in the responsiveness to circulating endogenous β-agonists shown in Figure 3 [34,35]. Thus, it was suggested that down-regulation of ADBR2 could play a role in the timing of labor, especially as ADRB2 agonists in some cases appear to prevent preterm delivery [36,37]. This led us, and other authors, to investigate the association between the ADRB2 rs1042713 polymorphism and SPTB. While case-control association studies conducted in the Hungarian and Hispanic populations proposed that homozygosity for ADRB2 rs1042713 (AA genotype) protects against SPTB [31,32], our study and studies in the Korean and Turkish populations have not found any evidence of genotype AA effect on SPTB [30,33]. Both studies reporting an association between ADRB2 rs1042713 polymorphism and preterm birth (PTB) had small sample sizes, especially in the group of patients suffering from PTB, which leads to a lower statistical power to detect small effects of the studied polymorphism. The results of the studies could also be influenced by ethnical diversity among the participants. The results of genetic association studies quite frequently fail to be reproduced in subsequent studies, either because the original findings are false-positive reports, or because the small genetic effects were not detectable [38]. Large sample sizes or meta-analysis are required in order to identify the small genetic effects of polymorphisms [39]. A meta analysis is a statistical tool that enables objective, quantitative synthesis of research findings, thus overcoming the problem of a small sample size and the inadequate statistical strength of genetic association studies [40]. To further investigate the role of the ADRB2 rs1042713 polymorphism and SPTB we performed a meta analysis of four previously published case-control association studies and our study [30,33]. The evidence for association was found neither under the recessive nor dominant genetic models. Alternatively, the previously published meta analysis of three reports, including both studies that found association [31,32] and studies by Ozkur et al. [33] and Dolan et al. [41], suggested a nominally significant association. Our study has some limitations. On the one hand, the study in the Slovenian population had limited power to detect small effects of the studied polymorphism. On the other hand, the size of studies included in the meta analysis was small and of heterogeneous genetic background. Additionally, we found evidence of moderate heterogeneity under the dominant genetic model in our meta analysis. We only included studies in the English language; therefore, we might have missed potential association studies linking ADRB2 rs1042713 to SPTB. In conclusion, both the association study in the Slovenian population and meta analysis showed no evidence of an association between ADRB2 rs1042713 and SPTB. Further larger association studies on the topic are needed to reach a more definite conclusion. Declaration of Interest. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. Funding. This study was supported by a grant P3- 0326 from the Slovenian Research Agency (to B. Peterlin).

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