Zhao, Teng, Liu, Yun, Wang, Peng, Li, Sheng, Zhou, Daizhan, Zhang, Di, Chen, Zhou, Wang, Ting, Xu, He, Feng, Gouyin, He, Lin, and Yu, Lan
Background: Bipolar disorder is a widespread and severe brain disorder that is strongly affected by genetic factors. The PDZ and LIM domain 5 (PDLIM5) gene encodes a protein as an Enigma homologue LIM domain protein, which has been widely reported as being expressed in various brain regions. The analysis of DNA microarrays in the frontal lobes of patients with bipolar disorder has indicated changes in the expression level of PDLIM5, and subsequent studies have suggested that PDLIM5 might play a role in susceptibility to bipolar disorder. We sought to examine the association between PDLIM5and bipolar disorder. Methods: We recruited 502 patients with bipolar disorder and 507 controls from Anhui Province, China. We conducted a case-control study of 4 single-nucleotide polymorphisms (SNPs) of PDLIM5that have been reported to be significantly associated with bipolar disorder in the Japanese and Chinese population: rs10008257, rs2433320, rs2433322 and rs2438146. Results: We found that rs2433322 showed significantly different frequencies between patients and controls (p = 0.002). Three of the SNPs, rs10008257, rs2433320 and rs2438146, showed no statistical association with bipolar disorder; however, haplotypes constructed from 3 SNPs, rs2433320, rs2433322 and rs2438146, were significantly associated with bipolar disorder (global p = 0.004 after Bonferroni correction). Limitations: Our genetic association study only offered evidence for susceptibility of PDLIM5 to bipolar disorder, but the positive SNP rs2433322 could not indicate a direct cause of this complicated brain disorder. In addition, the 4 tagged SNPs that we selected could not cover the whole region of PDLIM5, thus additional reproducible studies of more SNPS in large non-Asian populations are needed. Conclusion: Our results suggest that PDLIM5 might play a role in susceptibility to bipolar disorder among the Chinese Han population. Contexte: Le trouble bipolaire est un trouble mental repandu et grave dont la composante genetique est importante. Le gene 5 des domaines PDZet LIM5 (PDLIM5) encode une proteine sous forme de proteine homologue enigmatique du domaine LIM qui, selon de nombreux rapports, est exprimee dans diverses regions du cerveau. L'analyse de microreseaux d'ADN provenant du lobe frontal de patients atteints de trouble bipolaire a revele la presence de variations du taux d'expression du PDLIM5et selon des analyses subsequentes, ce dernier pourrait jouer un role dans la predisposition au trouble bipolaire. Nous avons voulu etudier le lien entre le PDLIM5et le trouble bipolaire. Methodes: Nous avons recrute 502 patients atteints de trouble bipolaire et 507 participants temoins dans la province d'Anhui en Chine. Nous avons procede a une etude cas-temoins sur 4 polymorphismes de nucleotides simples (PNS) du PDLIM5qui seraient significativement associes au trouble bipolaire dans les populations japonaises et chinoises, soit les PNS rs10008257, rs2433320, rs2433322 et rs2438146. Resultats : Nous avons decouvert que le rs2433322 se manifestait a des frequences significativement differentes entre les patients et les temoins (p = 0,002). Trois des PNS, le rs10008257, le rs2433320 et le rs2438146, n'ont presente aucun lien statistique avec le trouble bipolaire. Toutefois, les haplotypes elabores a partir de 3 PNS, soit le rs2433320, le rs2433322 et le rs2438146, ont ete significativement associes au trouble bipolaire (p global = 0,004 apres correction de Bonferroni). Limites : Notre etude sur ce lien genetique n'a fourni des preuves qu'en regard de la predisposition des participants porteurs du PDLIM5 au trouble bipolaire, mais un PNS rs2433322 positif n'a pas pu etre considere comme une cause directe de ce trouble mental complexe. De plus, les 4 PNS marques qui ont ete selectionnes ne couvrant pas toute la region du PDLIM5, il faudra proceder a d'autres etudes de reproductibilite avec un plus grand nombre de PNS aupres d'importantes cohortes non asiatiques. Conclusion : Selon nos resultats, le PDLIM5pourrait jouer un role dans la predisposition au trouble bipolaire dans la population chinoise d'ascendance Han., Introduction Bipolar disorder, or manic-depressive illness, is a frequent, severe brain disorder characterized by dramatic recurrent episodes of mania and depression that affect mood, energy and ability to function. The [...]