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


CONCLUSIONS
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.
Zhao
Teng
T
Institute for Nutritional Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Liu
Yun
Y
Wang
Peng
P
Li
Sheng
S
Zhou
Daizhan
D
Zhang
Di
D
Chen
Zhuo
Z
Wang
Ting
T
Xu
He
H
Feng
Guoyin
G
He
Lin
L
Yu
Lan
L
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D003198:Computer Simulation; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D060588:LIM Domain Proteins; D015810:Linkage Disequilibrium; D008297:Male; D009010:Monte Carlo Method; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D012984:Software
D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; C512485:PDLIM5 protein, human