Novel SNARE complex polymorphisms associated with Multiple Sclerosis: Signs of Synapthopathy in Multiple Sclerosis

Background: The role of axonal degeneration on disability in patients with multiple sclerosis is well known and the synapthopathy has recently become an important issue.

Aims: To investigate possible roles of selected synaptic and presynaptic membrane protein genetic polymorphisms (VAMP2, SNAP-25, Synaptotagmin, Syntaxin 1A) in patients with multiple sclerosis.

Study Design: Case-control study.

Methods: One hundred and twenty-three patients with multiple sclerosis and 192 healthy controls were included. We analyzed the functional polymorphisms of specific SNARE complex proteins (VAMP2, Synaptotagmin XI, Syntaxin 1A and SNAP-25) by polymerase chain reaction.

Results: The study indicated significant differences for the genotype and allele distribution of 26 bp Ins/Del polymorphisms of VAMP2 between multiple sclerosis and control subjects; Del/Del genotype and Del allele of VAMP2 were more frequent in patients with multiple sclerosis (p=0.011, p=0.004), respectively. Similarly, Ddel polymorphism of SNAP-25 gene C/C genotype (p=0.059), Syntaxin 1A T/C and C/C genotypes (p=0.005), and Synaptogtagmin XI gene C allele (p=0.001) observed more frequently in patients with multiple sclerosis. CC, Syntaxin rs1569061 1A gene for 33-bp promoter region TC haplotypes and Synaptotagmin XI gene has been shown to be associated with increased risk for multiple sclerosis (p = 0.012). Similarly, GC haplotype for rs3746544 of SNAP-25 gene and rs1051312 of SNAP-25 gene were found to be an increased risk for multiple sclerosis (p=0.022).

Conclusion: The genetic polymorphisms of SNARE complex proteins, which have critical roles in synaptic structure and communication, may play a role in the development of multiple sclerosis.