1984A/G adrenomedullin (rs3814700) gene polymorphism: can it be responsible for unexplained recurrent early pregnancy loss?

Abstract

IntroductionRecurrent miscarriage (RM) is three or more consecutive pregnancy losses before 22 gestational weeks [1]. The prevalence is approximately 0.8-1.4%, if only clinical RM (evidence of pregnancy with ultrasonographic and histologic findings) is taken into account; the prevalence is 2-3%, if also biochemical losses (urinary HCG positivity with no evidence of sonographic or histologic endometrial findings) are taken into consideration (2). In fact, there is a "rule of 30%'s" regarding the outcome of conceptions: 30% of them are lost before they implant into the endometrium. Further 30% of them are lost after the implantation; however, before the next menstrual period begins. So, only 30% of them end up in live birth (3). The etiology of RM is heterogeneous and the current data cannot be able to cover all the aspects of RM. Still approximately 50% of RM is unexplained. The well-known factors are classified as genetic, immunologic factors, thrombophilia, endocrinological causes, uterine malformations and obesity (2-5). Due to exaggerated oxidative stress, uterine natural killer cells via increased angiogenesis during the implantation period have been thought as a cause for idiopathic RM (6). Recent studies have showed that adrenomedullin (ADM) was important in angiogenesis, extracellular cytotrophoblast migration and placentation (7,8). The normal physiological maternal adaptation to the pregnancy occurs with the increased serum ADM levels (8). In compromised pregnancies such as preeclampsia -a result of defective placentation-, the increase in ADM levels does not occur (8).It is showed that GG genotype for ADM gene causes a decrease in ADM production, whereas AA genotype is associated with increased ADM levels. -1984A>G variant in the promoter region of the ADM gene, which probably decreases adrenomedullin transcription and, in consequence, decreases ADM concentration (9). From that point of view, idiopathic RM may result due to defective placentation and implantation process associated with altered ADM function and levels. So, we Abstract Objective: The etiology of recurrent miscarriage (RM) is heterogeneous and the current data cannot be able to cover all the aspects of RM. Adrenomedulline (ADM) has been very popular with the discovery of vital functions in maintaining an uneventful pregnancy. Idiopathic RM may result due to defective placentation and implantation process associated with altered ADM function and levels. So, we hypothesized that increased ADM gene polymorphism could play a role in idiopathic RM cases Methods: This prospective case-control study consisted of 60 women; 30 of whom had three consecutive pregnancy losses, who admitted to the outpatient clinic of department of obstetrics and gynecology or department of genetic at our tertiary center. Genomic DNA was extracted from peripheral blood and the frequency of genotypes and alleles of -1984A>G ADM (rs3814700) gene polymorphism was examined by polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP) method Results...