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PTPRD fluctuation in pregnancy with and without Restless Legs Syndrome



Manconi M.



The proposed project will bring together investigators from the University of Campinas (UNICAMP), and the Neurocenter of Southern Switzerland with related scientific interest.

The Restless Leg Syndrome (RLS) is a common neurological sensorimotor disorder, manifested as an uncontrollable desire to move the body (legs) to relieve uncomfortable sensations (Berry et al., 2015). Symptoms appear or get worse during evening and night, interfering with sleep initiation and maintenance. Despite most typical in adults, RLS might affect children, adolescents, and pregnant women, with three components involved: genetic mechanism, dopaminergic dysfunction, and iron homeostasis (Manconi et al., 2021). Recently, Geng et al., (2022) demonstrated that serum levels of thyroid stimulating hormone (TSH), as well as a subclinical hypothyroidism were more represented in RLS patients. Dopaminergic system is well-kown linked with the hypothalamic-pituitary-thyroid (HPT) axis.

RLS affects women more frequently than men, with a reported 30–50% higher prevalence in women. During pregnancy, around 25% of women experience a transient form of RLS, with a dysfunction in iron metabolism and/or high estrogen levels that might contribute to RLS. During pregnancy, RLS symptoms peak in the third trimester and resolve around childbirth (Manconi et al., 2012). The quality of sleep altered during pregnancy can cause problems such as altered mental functioning, decreased daytime functioning, perinatal depression, hypertension, and diabetes. Sleep deprivation has been associated with adverse maternal and neonatal outcomes, including low birth weight, intrauterine growth retardation, preterm labor, operative delivery, and postpartum depression (Sharma et al., 2016).

Studies show that variations in the PTPRD gene (Protein Tyrosine Phosphatase Receptor Type Delta) may increase the chance of developing RLS. Allelic variants of PTPRD gene have been described in association with RLS at a significance level that withstands correction for multiple testing in a genome-wide analysis for common variants. The receptor-type protein tyrosine phosphatase D (PTPRD) gene encodes a cell adhesion molecule likely to influence the development of addiction and locomotion, and connections of sleep-related brain circuits where PTPRD is expressed.

In addition, genome-wide association studies (GWASs) showed that two single nucleotide polymorphisms (SNPs) (rs17584499 and rs649891) in the protein tyrosine phosphatase receptor type D (PTPRD) were associated with type 2 diabetes (T2D) (Tsai et al., 2010). Chen et al., (2016) suggested that PTPRD loci are candidate susceptibility regions that have some marker SNPs for gestational diabetes mellitus (GDM) in Han Chinese.

However, until the present moment, no relationship has yet been established between PTPRD and pregnancy related RLS.

Therefore, the main objective of this proposal is to evaluate PTPRD fluctuation in pregnancy with and without RLS. Furthermore, we believe it is important to analyze the relationship between TSH and RLS in pregnant women.

Additional information

Start date
End date
4 Months
Funding sources
Swiss National Science Foundation / Scientific Exchanges