ADH1B and ALDH2 polymorphisms and restless legs syndrome during pregnancy: A cross-sectional study during 2023-2025

The prevalence of restless legs syndrome (RLS) among Japanese pregnant women surveyed from 2020 to 2021 was 17.2%, which is higher than that in the general adult population. The onset of this condition involves various factors against a background of genetic predisposition. The presence of the ALDH2*2 allele has been linked to Parkinson's disease, but its association with RLS remains unexamined. This study aimed to clarify the relationship between ALDH2 polymorphism as well as ADH1B polymorphism-already reported to be associated with RLS-and RLS in pregnant women.

This study included 200 pregnant women in their third trimester. The survey was conducted from September 2023 to July 2025. Participants answered questionnaires on background factors and sleep/wake patterns, and DNA was extracted from somatic cells obtained by swabbing buccal mucosa using a cotton swab. The ALDH2 rs671 and ADH1B rs1229984 polymorphisms were determined.

The prevalence of RLS (95% confidence interval) during the survey period was 24.5% (18.7-21.1%). No association was identified between ALDH2 and ADH1B polymorphisms and RLS. Furthermore, no correlation was observed between ALDH2 and ADH1B polymorphisms and variables such as sleep duration, chronotype, insomnia symptoms, or daytime sleepiness, except for the relationship between ADH1B polymorphism and evening chronotype.

The prevalence of RLS among pregnant women has increased compared to the previous survey conducted using the same methodology. The ADH1B polymorphism was suggested to be linked with chronotype; however, no association was found between the ADH1B or ALDH2 polymorphisms and other sleep-wake phenotypes, including RLS.