rs1801968

This comprehensive literature review examines the role of single-nucleotide polymorphisms (SNPs) and genetic variants in dystonia susceptibility, reviewing 43 published studies (2001-2017) across 29 genes. Key findings include associations of TOR1A variants (rs1182, rs1801968, rs35153737) with focal dystonia, BDNF rs6265 (Val66Met) with cervical dystonia and blepharospasm, and preliminary GWAS-identified variants in ARSG (rs11655081, rs61999318) and NALCN with dystonia risk. The review concludes that genetic factors confer dystonia susceptibility through multiple pathways, though many associations require validation in larger cohorts.

This association study of 263 North American patients with focal or segmental dystonia found a strong protective association between the deletion allele at the Mtdel SNP (rs3842225) in the TOR1A gene and reduced risk of dystonia (OR=0.59, p=0.007), particularly for cervical dystonia (OR=0.48, p=0.002). The D216H SNP (rs1801968) showed no significant association. The findings suggest genetic variability in the TOR1A locus contributes to focal dystonia risk, though results vary by population.

This study attempted to replicate findings by Risch et al. showing that the rs1801968 H allele (p.Asp216His) in TOR1A has a protective effect on DYT1 dystonia penetrance in European populations. The French study of 53 index cases found that all TOR1A c.907delGAG mutation carriers had the D allele in cis, but failed to replicate the protective trans effect of the H allele observed in American families, suggesting population-specific genetic modifiers.