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Letter to the Editor: No evidence for association between the EIF2B5 gene and multiple sclerosis in French families

Dear Editor – In their recent paper, Lucas, et al. [1] tested the Arg113His mutation (EIF2B5 gene), mostly involved in the childhood ataxia with central hypomylination/vanishing white matter (CACH/VWM) leukodystrophy, in a cohort of 101 patients with multiple sclerosis (MS). The authors showed no implication of the Arg113His mutation in MS susceptibility. However, similarities exist between MS and adult onset forms of CACH/ VWM, confirming the interest in testing the EIF2B5 gene as a susceptibility factor for MS [2]. Indeed, both neurodegenerative disorders involve a progressive demyelization of the cerebral white matter, typically characterized by relapsing–remitting phases precipitated by stress. The eukaryotic initiation factor (eIF2B) mutated in CACH/VWM patients is involved in the regulation of protein synthesis particularly under stress conditions. This key regulator role could explain the stress sensitivity of eIF2B-related disorders. In MS, stress has been largely reported as a precipitating factor, but never studied as a susceptibility factor. We tested the EIF2B5 gene as a candidate locus involved in MS susceptibility in a sample of French MS trio families. A total of 930 individuals, including 310 MS affected patients and both parents, have been genotyped for three single nucleotide polymorphisms (SNPs) localized in the EIF2B5 gene: rs2292611 in the promoter (het = 0.35), rs843358 in exon 13 (het = 0.43) and rs843359 in intron 12 (het = 0.50). We applied the combination test [3] to test for potential association between these three EIF2B5 SNPs and MS. This method has been shown to be powerful in detecting the role of a candidate gene even when several functional SNPs interact and have small individual effects. The combination test was carried out using the FamHap software [4]. As shown in Table 1, the combination of the two SNPs, rs983358 and rs2292611, has a pvalue of 0.036. However, this p-value becomes non-significant (0.114) after correcting for multiple testing. Our study does not provide evidence for the involvement of EIF2B5 in MS susceptibility. Acknowledgements