A variant in the 5-hydroxytryptamine (serotonin) receptor 5A (HTR5A) gene may be involved in the pathogenesis of bipolar disorder, says an international team of scientists, although they urge caution in interpreting the findings.

Despite a wealth of research into the etiology of bipolar disorder and evidence to suggest that it is the result of an interaction between genetic and environmental factors, no single gene has been identified as being definitively associated with the disorder.

Yusuke Nakamura, from the University of Tokyo in Japan, and colleagues genotyped 94 bipolar disorder patients and 184 healthy controls from Bulgaria for 191 single nucleotide polymorphisms (SNPs) in 65 candidate genes using TaqMan and/or Invader assays.

In all, 17 SNPs were significantly associated with bipolar disorder and these were further genotyped in an additional set of 78 bipolar disorder patients and 372 controls, with the results pooled with the previous analysis to give a combined set of 172 patients and 556 controls.

The most significant association with bipolar disorder was found for the rs1800883 SNP in a promoter region of the HTR5A gene, which was unaffected by sequential Bonferroni correction, the team notes in the Journal of Affective Disorders.

Analysis revealed that 56.7% of the patients were homozygous for the G risk allele, compared with 42.1% of controls, giving an odds ratio of 1.80. In addition, the risk allele was more common in patients than in controls, at 73.7% versus 62.1%.

A weak association was also found for the rs6265 SNP located in exon 2 of the brain-derived neurotrophic factor gene, with the risk C allele more frequently seen in patients than controls, while a possible association was observed for the rs5443 SNP in exon 10 of the guanine nucleotide binding protein, beta polypeptide 3 gene. However, neither survived Bonferroni correction.

“In conclusion, our findings suggest that HTR5A gene could be one of many genes of importance in the etiology of bipolar disorder in the Bulgarian population, but the effect by the genetic substitution seemed to be small even if the association is further confirmed,” the team writes.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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