Association study of p11 gene with major depressive disorder, suicidal behaviors and treatment response.
The p11 protein (also called S100A10), which plays a pivotal role in the dynamic modulation of serotonergic 1B receptor function, has been implicated in the pathogenesis of major depressive disorder (MDD) and the therapeutic mechanisms of antidepressant action. Humans and mice with depression have lower central p11 levels, and treatment with antidepressant agents raises p11 levels in animals. Furthermore, brain p11 mRNA expression is lower in post mortem brains from patients who were suffering from depression and had committed suicide compared with control subjects who had died from other causes. From the above findings, the p11 gene may be considered a candidate gene for the investigation of MDD susceptibility, response to antidepressants or the likelihood of attempting suicide. Three p11 polymorphisms were genotyped in 470 patients with MDD and 447 normal controls. No significant association with MDD was discovered in single locus or haplotype analyses. The analysis for genotypic effects showed no significant association between any of the three p11 single nucleotide polymorphisms (SNPs) and MDD therapeutic response. With regard to the risk of suicide attempt, 51 of the 470 MDD patients were found to have attempted suicide in the depressive episode during which they were monitored. No significant association with suicide attempt was shown in both the alleles and genotypes of single loci or of haplotypes constructed from these three p11 polymorphisms. Our findings suggest that p11 genetic variants do not play a major role in the MDD susceptibility, antidepressant therapeutic response or the risk of suicide attempt in MDD.
Department of Psychiatry, Mackay Memorial Hospital, Taipei, Taiwan.
Ruu-Fen
RF
Tzang
Chen-Jee
CJ
Hong
Ying-Jay
YJ
Liou
Younger W-Y
YW
Yu
Tai-Jui
TJ
Chen
Shih-Jen
SJ
Tsai
D000328:Adult; D017306:Annexin A2 / Q000235:genetics*; D000928:Antidepressive Agents / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D003866:Depressive Disorder / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D009418:S100 Proteins / Q000235:genetics*; D013406:Suicide, Attempted / Q000523:psychology*; D000099248:S100 Calcium Binding Protein A10
D017306:Annexin A2; D000928:Antidepressive Agents; D012333:RNA, Messenger; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10