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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.

Long noncoding RNA HOTAIR polymorphisms and susceptibility to bipolar disorder: a preliminary case–control study