# MDGA1 Gene Variants and Risk for Restless Legs Syndrome

## TL;DR

This study found that common genetic variations in the MDGA1 gene are not linked to the risk of developing restless legs syndrome in a Spanish population.

## Contribution

The study provides evidence against an association between MDGA1 gene variants and iRLS in a Caucasian Spanish cohort.

## Key findings

- Common MDGA1 gene variants showed no significant difference in frequency between RLS patients and healthy controls.
- Genotype frequencies were not correlated with age at onset, severity, family history, or drug response in RLS patients.
- Results suggest MDGA1 missense SNVs are not risk factors for iRLS in the studied population.

## Abstract

The MAM domain-containing glycosylphosphatidylinositol anchor 1 (MDGA1) gene, which encodes a protein involved in synaptic inhibition, has been identified as a potential risk gene for restless legs syndrome. A recent study in the Chinese population described increased MDGA1 methylation levels in patients with idiopathic RLS (iRLS) compared to healthy controls. In this study, we investigated the possible association between the most common variants in the MDGA1 gene and the risk for iRLS in a Caucasian Spanish population. We assessed the frequencies of MDGA1 rs10947690, MDGA1 rs61151079, and MDGA1 rs79792089 genotypes and allelic variants in 263 patients with idiopathic RLS and 280 healthy controls using a specific TaqMan-based qPCR assay. We also analyzed the possible influence of the genotype frequencies on several variables, including age at the onset of RLS, gender, a family history of RLS, and response to drugs commonly used in the treatment of RLS. The frequencies of the genotypes and allelic variants of the three common missense SNVs studied did not differ significantly between RLS patients and controls, neither in the whole series nor when analyzing each gender separately; were not correlated with age at onset and the severity of RLS assessed by the International Restless Legs Syndrome Study Group Rating Scale (IRLSSGRS); and were not related to a family history of RLS or the pharmacological response to dopamine agonists, clonazepam, or gabaergic drugs. Our findings suggest that common missense SNVs in the MDGA1 gene are not associated with the risk of developing idiopathic RLS in Caucasian Spanish people.