471: Functional polymorphism of serotonin transporter gene are associated with an increased risk of early pregnancy loss

Adverse pregnancy outcome (APO); repeated early pregnancy loss (REPL) and preterm birth (PTB) are determined by a multitude of factors, among which emotional and stress behaviors. These in turn, are mediated by serotonin receptor/ transporter (SLC6A4, 5-HTT). 5-HTT gene modulation was shown to impact on mitogenic capacity and aromatase activity of trophoblasts, and myometrial contractility. Functional polymorphisms of the 5' region of the 5-HTT gene are associated with lower transcriptional efficiency and serotonin uptake. Thus, we sought to determine the relationship between APO and 5-HTT gene variants. Prospective observational study of 76 women with PTB (<35weeks) as compared to 265 women with term uncomplicated birth, the controls. REPL was identified by medical records coding in both groups. Blood samples were compared for two functional polymorphisms of HTT-5; C(-1019)G polymorphism of the 5-HT1A receptor gene promoter and the 5-HTT-linked polymorphic region (5-HTTLPR) that produces a L (long, greater expressing) and S (short, lesser expressing) alleles. Statistics: Kruskal-Wallis & χ2 tests. PHASE 2.0.2 for allele frequencies and haplotype pairs, exact logistic regression. Both groups were similar with respect of mean age, ethnical origin, educational status, smoking habits, and area of residence. Hardy-Weinberg equilibrium was observed for both genes. While the pregnancy rate was similar between the groups, the women carrying the S (lesser expressing ) allele of 5-HTTLPR had a significantly higher REPL rate compared to the L (functional) allele, mean 0.6±0.90 vs 1.1±1.55 p=0.0046. The carriers of both 5HT1A-G and 5-HTTLPR variants showed no increased risk for either present or past PTB. This study suggests a plausible role for the serotonin gene variants in the early pregnancy establishment. We propose 5-HTTLPR gene functional polymorphism as moderators between personality traits and REPL and a target for future research and therapy.