Two functional promoter polymorphisms of neuregulin 1 gene are associated with progressive forms of multiple sclerosis

• Remyelination in MS lesions may depend on expression profile of growth factors.
• SNP rs6994992 of NRG1 gene is associated with progressive forms of MS.
• Primary progressive MS is associated with SNP rs7014762 of NRG1 gene.
• Progression of MS disease could be influenced by functional nucleotide variations of NRG1.
• Significant association may exist between male MS subjects and rs7014762 in NRG1.

Multiple sclerosis (MS) is an inflammatory, autoimmune, demyelinating disease of the central nervous system (CNS). Spontaneous remyelination happens in most of MS lesions but it is incomplete and inadequate and eventually fails in majority of lesions of damaged areas. According to the fact that the accuracy of this phenomenon depends on distinct temporal expression profiles of molecules, especially growth factors, we decided to study the association of two functional polymorphisms of NRG1 as a myelin-related growth factor which can promote oligodendrocyte proliferation and differentiation in CNS and PNS. SNP rs6994992 and SNP rs7014762 were genotyped by PCR-RFLP and mismatch PCR-RFLP methods, respectively, in 165 subjects with MS and 200 healthy controls. Totally, our results showed no significant difference in the allelic and genotype frequencies of these two NRG1 polymorphisms between MS patients and control group in Iranian population; but statistically significant association was found for the progressive forms of MS (secondary progressive-MS and primary progressive-MS) for functional SNP of rs6994992 polymorphism. Also, considering rs7014762 polymorphism frequencies, significant difference was observed between primary progressive MS group in comparison to the control group. Furthermore, when the samples were stratified by gender, significant association was revealed between male MS subjects and rs7014762 polymorphism. These results indicate that progression of MS disease could be influenced by functional nucleotide variations in NRG1 gene, which might have an impact on remyelination capacity in different patients.