Positive association between the PDLIM5 gene and bipolar disorder in the Chinese Han population

Positive association between the PDLIM5 gene and bipolar disorder in the Chinese Han population

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J Psychiatry Neurosci 2010; 34(3): 199-204

Teng Zhao, PhD; Yun Liu, PhD; Peng Wang, MB; Sheng Li, PhD; Daizhan Zhou, PhD; Di Zhang, PhD; Zhuo Chen, PhD; Ting Wang, BS; He Xu, PhD; Guoyin Feng, MB;
Lin He, PhD; Lan Yu, PhD

Zhao, Liu, Li, Zhou, Zhang, Chen, Wang, Xu, He, Yu — Institute for Nutritional Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai; Wang — The Fourth People’s Hospital of Wuhu, Anhui Province; Li, Xu, He, Yu — Bio-X Center, Shanghai Jiao Tong University; Feng — Shanghai Institute of Mental Health; He — Institutes of Biomedical Sciences, Fudan University, Shanghai, China

Abstract

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 PDLIM5 and 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 PDLIM5 that 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.

Conclusions: Our results suggest that PDLIM5 might play a role in susceptibility to bipolar disorder among the Chinese Han population.


Submitted Feb. 17, 2008; Revised Apr. 7, Jun. 16, 2008; Accepted Jun. 16, 2008

Acknowledgements: This work was supported by grants from the Chinese Academy of Sciences (KSCX2-YW-R-01), the National Natural Science Foundation of China, the national S973 and 863 Programs, and the Shanghai Municipal Commission for Science and Technology. Shanghai Leading Academic Discipline Project (B205).
We appreciate the contribution of all of the members participating in this study, as well as of the psychiatrists who helped us in the diagnosis.

Competing interests: None declared.

Contributors: Drs. Zhao, Liu, Zhou, Zhang, Chen, Feng, Yu and He designed the study. Drs. P. Wang, Li, Xu and Feng acquired the data, which Drs. Zhao, Liu, Zhou, Zhang, Chen and T. Wang analyzed. Dr. Zhao wrote the article, which all other authors reviewed. All authors approved the final version for publication.

Correspondence to: Dr. L. Yu or Dr. L. He, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Rd., Shanghai 200031, China or Bio-X Center, Shanghai Jiao Tong University, Hao Ran Bldg., 1954 Hua Shan Rd., Shanghai 200030, China; fax 86 21 62822491; helin@bio-x.cn