LINGO1 rs9652490 and rs11856808 polymorphisms are not associated with risk for multiple sclerosis

Abstract

Background: Some recent experimental data suggest a possible role of LINGO-1 in the pathogenesis of multiple sclerosis (MS). In an attempt to identify genetic biomarkers related to MS susceptibility, we genotyped two common SNPs in the LINGO1 gene which have been associated to other neurological conditions, in patients with MS and in healthy subjects. These SNPs are linked to several SNPs within the LINGO1 gene, especially in individuals of Oriental or Caucasian descent.

Methods: We analyzed the allelic and genotype frequency of two LINGO1 variants (rs9652490 and rs11856808) in 293 patients with MS and 318 healthy controls, using KASPar assays.

Results: LINGO1 rs9652490 and rs11856808 allelic and genotype frequencies did not differ significantly between MS patients and controls. The minor allele frequencies for rs9652490 were 0.171 (95% CI = 0.140-0.201) and 0.167 (95% CI = 0.138-0.196 for cases and controls respectively (p = 0.853). For rs11856808 the minor allele frequencies were 0.317 (95% CI = 0.280-0.355) and 0.310 (95% CI = 0.274-0.346) for cases and controls, respectively (p = 0.773). Allele and genotype frequencies were unrelated with the age of onset of MS, gender, and clinical course of MS. In addition, haplotype analyses did not reveal any putative risk related to haplotypes.

Conclusions: These results suggest that LINGO1 rs9652490 and rs11856808 polymorphisms are not related with risk for MS. This study adds to other published evidence indicating that, to date, the LINGO1 SNPs studied here could be useful risk biomarkers of developing essential tremor, but not other movement disorders.

Figure 1

Scheme and linkage analysis of the SNPs analyzed in this study. The linkage figure was composed with Haploview Ver. 3, release R-2, excluding individuals with > 50% missing genotypes, according to the standard colour scheme (D’/LOD), and the D’ values (×100) are shown when relevant. Top: The area covers the whole LINGO1 gene as well as the 3’ flanking region. The SNPs tested are marked at the right side of the figure. These data correspond to Caucasian individuals (Utah residents with ancestry from northern and western Europe). Bottom: Linkage figures focusing on the two SNPs tested and six SNPs located within the LINGO1 gene. The populations correspond to: CEU, Utah residents with ancestry from northern and western Europe; ASW, African ancestry in Southwest USA; JPT, Japanese in Tokyo, Japan; CHB, Han Chinese in Beijing, China; MXL, Mexican ancestry in Los Angeles, California; TSI, Tuscany in Italia. (see the website http://www.sanger.ac.uk/resources/downloads/human/hapmap3.html).