Association of ESR1 Polymorphisms with Susceptibility to Migraine: A Meta-Analysis and Trial Sequential Analysis.

Abstract

Background: Migraine is a highly prevalent and incapacitating neurological disorder mostly characterised by recurring attacks of moderate to severe throbbing and pulsating pain on one side of the head. The role of estrogen in migraine has been well documented. Although genetic variations in the ESR1 gene have been associated with an increased risk of developing migraine, the findings are inconsistent. We performed a meta-analysis of previously published articles considering four important single nucleotide polymorphisms in the ESR1 gene (rs1801132, rs2228480, rs2234693, and rs9340799) to explore their possible association with the development of migraine and its clinical phenotypes.

Materials and methods: We thoroughly searched literature databases, including PubMed, Science Direct, and Scopus until March 14, 2024, to identify the relevant reports. We utilized GPower software v.3 to assess the power of each report included in the meta-analysis and Comprehensive Meta-analysis v4 for all meta-analysis-related analyses. We employed funnel plots and Egger's regression test to identify publication biases within each genetic comparison model. We used Cochrane Q statistics, probability value, and I² to assess heterogeneity.

Results: After applying predefined criteria, a meta-analysis was conducted with 11 relevant studies comprising 3835 cases of migraine and 3655 healthy individuals. The analysis indicated a strong correlation between ESR1 polymorphisms (rs2228480 and rs9340799) and the likelihood of developing migraine. Furthermore, the subgroup analysis showed that rs2228480 is associated with susceptibility to migraine in both Caucasians and Asians. Additionally, rs2234693 variants were found to be linked with the development of migraine with aura. However, the trial sequential analysis suggested that more case-control studies are necessary to establish the definitive role of ESR1 variants in migraine.

Conclusions: ESR1 variants (rs2228480, rs2234693, and rs9340799) are associated with an increased risk of migraine and related phenotypes. However, further studies are needed to establish a definitive conclusion.