Isolated dystonia is a common movement disorder often caused by genetic mutations, although it is predominantly sporadic in nature. Common variants of dystonia-related genes were reported to be risk factors for idiopathic isolated dystonia. In this study, we aimed to analyse the roles of previously reported GTP cyclohydrolase (GCH1) and Torsin family 1 member A (TOR1A) polymorphisms in an Indian isolated dystonia case-control group. A total of 292 sporadic isolated dystonia patients and 316 control individuals were genotyped for single-nucleotide polymorphisms (SNPs) of GCH1 (rs3759664:G > A, rs12147422:A > G and rs10483639:C > G) and TOR1A (rs13300897:G > A, rs1801968:G > C, rs1182:G > T and rs3842225:G > Δ) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by direct Sanger sequencing. The statistical significance of allelic, genotypic and haplotypic associations of all of the SNPs were evaluated using the two-tailed Fisher exact test. The minor allele (A) of rs3759664 is significantly associated with isolated limb dystonia as a risk factor (p = 0.005). The minor allele (C) of rs1801968 is strongly associated with isolated dystonia (p < 0.0001) and most of its subtypes. The major allele of rs3842225 (G) may act as a significant risk factor for Writer’s cramp (p = 0.03). Four different haplogroups comprising of either rs1182 or rs3842225 or in combination with rs1801968 and rs13300897 were found to be significantly associated with isolated dystonia. No other allelic, genotypic or haplotypic association was found to be significant with isolated dystonia cohort or its endophenotype stratified groups. Our study suggests that TOR1A common variants have a significant role in isolated dystonia pathogenesis in the Indian population, whereas SNPs in the GCH1 gene may have a limited role.

孤立性肌张力障碍是一种常见的运动障碍，通常由基因突变引起，尽管它主要是散发性的。据报道，肌张力障碍相关基因的常见变异是特发性孤立性肌张力障碍的危险因素。在本研究中，我们旨在分析先前报道的 GTP 环化水解酶 ( GCH1 ) 和 Torsin 家族 1 成员 A ( TOR1A ) 多态性在印度孤立性肌张力障碍病例对照组中的作用。对总共 292 名散发性孤立性肌张力障碍患者和 316 名对照个体进行了GCH1（rs3759664:G > A、rs12147422:A > G 和 rs10483639:C > G）和TOR1A 的单核苷酸多态性 (SNP) 的基因分型(rs13300897:G > A, rs1801968:G > C, rs1182:G > T 和 rs3842225:G > Δ) 使用聚合酶链反应限制性片段长度多态性 (PCR-RFLP) 并通过直接 Sanger 测序确认。使用双尾 Fisher 精确检验评估所有 SNP 的等位基因、基因型和单倍型关联的统计显着性。rs3759664 的次要等位基因 (A) 与作为危险因素的孤立性肢体肌张力障碍显着相关 ( p  = 0.005)。rs1801968 的次要等位基因 (C) 与孤立性肌张力障碍 ( p  < 0.0001) 及其大多数亚型密切相关。rs3842225 (G) 的主要等位基因可能是 Writer 痉挛的重要危险因素 ( p = 0.03）。发现包括 rs1182 或 rs3842225 或与 rs1801968 和 rs13300897 组合的四个不同单倍群与孤立性肌张力障碍显着相关。在孤立的肌张力障碍队列或其内表型分层组中，没有发现其他等位基因、基因型或单倍型关联是显着的。我们的研究表明，TOR1A常见变异在印度人群的孤立性肌张力障碍发病机制中具有重要作用，而GCH1基因中的SNP可能作用有限。