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Multiple sclerosis (MS) is a sex-specific autoimmune disease involving central nervous system. Previous studies determined that macrophage migration inhibitory factor (MIF) and its homologue D-dopachrome tautomerase (DDT) sex-specifically affect MS progression. Moreover, other studies reported that rs755622 polymorphism in promoter region of  MIF  gene is associated with risk of MS and affects the promoter activity to regulate  MIF  expression in a sex-specific way. Given that  MIF  and  DDT  share a part of promoter sequence, we surmise that rs755622 can also regulate  DDT  expression in a sex-specific way. However, this has not yet been studied. Here, we used five large-scale expression quantitative trait loci (eQTLs) and two RNA-seq datasets from brain and blood to assess the potential influence of rs755622 variant on expression of  DDT  in different genders by the linear regression and differential expression analysis. The results show that the minor allele frequency of rs755622 and expression of  DDT  are significantly increased in males for MS subjects and this minor allele variant can significantly upregulate  DDT  expression for males but not females, which suggests that the regulation of  DDT  expression level by rs755622 can affect MS progression in males. These findings further support and expand conclusions of previous studies and may help to better understand the mechanisms of MS.

Genetic Variant rs755622 Regulates Expression of the Multiple Sclerosis Severity Modifier D-Dopachrome Tautomerase in a Sex-Specific Way