Abstract

Recent studies have shown that long noncoding RNAs contribute to the pathogenesis of bipolar disorder (BD). In this study, we genotyped four HOX Transcript Antisense Intergenic RNA (HOTAIR) gene polymorphisms to investigate if these variations could affect the risk of BD and its clinical subtypes. A total of 357 subjects, comprised of 194 BD patients and 163 age-matched healthy controls, were enrolled. Genotyping was carried out using PCR-RFLP and ARMS-PCR methods. We detected significant associations between the HOTAIR gene rs1899663 G/T, rs12826786 C/T, rs4759314 A/G, and rs920778 C/T polymorphism and the risk of BD under allelic, recessive, dominant, and codominant contrasted genetic models. The CT genotype of rs920778 C/T, GT genotype of rs1899663 G/T, and CT genotype of rs12826786 C/T polymorphisms enhanced the risk of BD type II (BDII). In contrast, the GG genotype of rs4759314 A/G polymorphism significantly diminished BDII risk by 83%. A positive association was noticed between CTTA and CTCG haplotypes of rs920778/rs1899663/rs12826786/rs4759314 and BD risk. Our findings reveal an interactive effect of HOTAIR polymorphisms on the development of BD and its subtypes. Further functional studies are needed to elucidate the role of these variations on HOTAIR expression and epigenetic status.

摘要

最近的研究表明，长的非编码 RNA 有助于双相情感障碍 (BD) 的发病机制。在这项研究中，我们对四个 HOX Transcript Antisense Intergenic RNA ( HOTAIR ) 基因多态性进行了基因分型，以研究这些变异是否会影响 BD 及其临床亚型的风险。共招募了 357 名受试者，包括 194 名 BD 患者和 163 名年龄匹配的健康对照。使用PCR-RFLP和ARMS-PCR方法进行基因分型。我们检测到HOTAIR之间的显着关联基因 rs1899663 G/T、rs12826786 C/T、rs4759314 A/G 和 rs920778 C/T 多态性和等位基因、隐性、显性和共显性对比遗传模型下的 BD 风险。rs920778 C/T的CT基因型、rs1899663 G/T的GT基因型和rs12826786 C/T多态性的CT基因型增加了BD II型（BDII）的风险。相比之下，rs4759314 A/G 多态性的 GG 基因型将 BDII 风险显着降低了 83%。rs920778/rs1899663/rs12826786/rs4759314 的 CTTA 和 CTCG 单倍型与 BD 风险之间存在正相关。我们的研究结果揭示了HOTAIR多态性对 BD 及其亚型发展的交互作用。需要进一步的功能研究来阐明这些变异对HOTAIR表达和表观遗传状态的作用。