Bipolar Disord. 2014 Mar;16(2):151-8. doi: 10.1111/bdi.12136.
The therapeutic action of lithium in bipolar mood disorder may be connected with its effect on biological rhythms. In the present study, an attempt was made to investigate an association between multiple single nucleotide polymorphisms (SNPs) and their haplotypes pertaining to four genes involved in regulation of biological rhythms [circadian locomotor output cycle kaput (CLOCK), aryl hydrocarbon receptor nuclear translocator-like (ARNTL), timeless circadian clock (TIMELESS), period circadian clock 3 (PER 3)], and the efficacy of lithium prophylaxis.
The study was performed on 115 patients with bipolar mood disorder (45 males, 70 females) with a mean age of 52 ± 12 years, with lithium prophylaxis for 22 ± 8 years, recruited from the outpatients in the Department of Psychiatry, Poznan University of Medical Sciences. The assessment of the lithium prophylactic response was made retrospectively using the Alda scale. Genotyping was done for nine SNPs of the CLOCK gene, 18 SNPs of the ARNTL gene, six SNPs of the timeless circadian clock (TIM) gene, and nine SNPs of the PER3 gene.
An association with the degree of lithium prophylaxis was found for six SNPs and three haplotype blocks of the ARNTL gene, and two SNPs and one haplotype block of the TIM gene. No association with SNPs or haplotypes of the CLOCK and PER3 genes was observed.
The results suggest that the ARNTL and TIM genes may be associated with the lithium prophylactic response in bipolar illness. This association may be related to the role of these genes in the predisposition to bipolar mood disorder. Of special interest may be polymorphisms of these genes involved both in the predisposition to bipolar mood disorder and the lithium response.
锂在双相情感障碍中的治疗作用可能与其对生物节律的影响有关。本研究试图探讨四个参与生物节律调节的基因（circadian locomotor output cycle kaput [CLOCK]、aryl hydrocarbon receptor nuclear translocator-like [ARNTL]、 timeless circadian clock [TIMELESS]、period circadian clock 3 [PER 3]）的多个单核苷酸多态性（SNP）及其单倍型与锂预防作用之间的关联。
该研究纳入了 115 名来自波兹南医科大学精神病学系门诊的双相情感障碍患者（45 名男性，70 名女性），平均年龄 52 ± 12 岁，锂预防治疗 22 ± 8 年。使用 Alda 量表回顾性评估锂预防的反应。对 CLOCK 基因的 9 个 SNP、ARNTL 基因的 18 个 SNP、TIM 基因的 6 个 SNP 和 PER3 基因的 9 个 SNP 进行了基因分型。
发现 ARNTL 基因的 6 个 SNP 和 3 个单倍型块以及 TIM 基因的 2 个 SNP 和 1 个单倍型块与锂预防程度相关。CLOCK 和 PER3 基因的 SNP 或单倍型与锂预防无关联。
结果表明，ARNTL 和 TIM 基因可能与双相情感障碍的锂预防反应有关。这种关联可能与这些基因在双相情感障碍易感性中的作用有关。这些基因中涉及双相情感障碍易感性和锂反应的多态性可能特别有趣。
