Case-control study of ADARB1 and ADARB2 gene variants in migraine.

Claudia F Gasparini,Bridget Maher,Larisa M Haupt,Astrid J Rodriguez-Acevedo,Heidi G Sutherland,Lyn R Griffiths,Elhame Khlifi

doi:10.1186/s10194-015-0511-y

Abstract

BackgroundMigraine causes crippling attacks of severe head pain along with associated nausea, vomiting, photophobia and/or phonophobia. The aim of this study was to investigate single nucleotide polymorphisms (SNPs) in the adenosine deaminase, RNA-specific, B1 (ADARB1) and adenosine deaminase, RNA specific, B2 (ADARB2) genes in an Australian case–control Caucasian population for association with migraine. Both candidate genes are highly expressed in the central nervous system and fit criteria for migraine neuropathology. SNPs in the ADARB2 gene were previously found to be positively associated with migraine in a pedigree-based genome wide association study using the genetic isolate of Norfolk Island, Australia. The ADARB1 gene was also chosen for investigation due to its important function in editing neurotransmitter receptor transcripts.MethodsFour SNPs in ADARB1 and nine in ADARB2 were selected by inspecting blocks of linkage disequilibrium in Haploview for genotyping using either TaqMan or Sequenom assays. These SNPs were genotyped in two-hundred and ninety one patients who satisfied the International Classification of Headache Disorders-II 2004 diagnostic criteria for migraine, and three-hundred and fourteen controls, and PLINK was used for association testing.ResultsChi-square analysis found no significant association between any of the SNPs tested in the ADARB1 and ADARB2 genes in this study and the occurrence of migraine.ConclusionsIn contrast to findings that SNPs in the ADARB2 gene were positively associated with migraine in the Norfolk Island population, we find no evidence to support the involvement of RNA editing genes in migraine susceptibility in an Australian Caucasian population.

Highlights

Migraine causes crippling attacks of severe head pain along with associated nausea, vomiting, photophobia and/or phonophobia
While genome wide association studies (GWAS) have shed new light on the types of genes involved in migraine susceptibility, many candidate gene association studies have focused on neurotransmitterrelated pathways, as these pathways are considered to play a significant role in the migraine process
We previously identified four single nucleotide polymorphisms (SNPs) forming a 22 kb haplotype block in ADARB2 (Table 1 and Figure 1) that were positively associated with migraine susceptibility in a pedigree-based GWAS of the population of Norfolk Island [11]

Summary

Introduction

Migraine causes crippling attacks of severe head pain along with associated nausea, vomiting, photophobia and/or phonophobia. The aim of this study was to investigate single nucleotide polymorphisms (SNPs) in the adenosine deaminase, RNA-specific, B1 (ADARB1) and adenosine deaminase, RNA specific, B2 (ADARB2) genes in an Australian case–control Caucasian population for association with migraine. Both candidate genes are highly expressed in the central nervous system and fit criteria for migraine neuropathology. Genes causing more common types of migraine have been identified from neurological, vascular and hormonal pathways and in 2010 the first functional variant to show linkage to familial MA was identified in TRESK, a potassium channel involved in neuronal excitability [10]. Genes affecting synthesis and activity of neurotransmitters, including RNA editing genes, are potential candidates for involvement in migraine susceptibility

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