Allelic association study between phospholipase A2 genes and bipolar affective disorder.

OBJECTIVES: In vivo studies demonstrating that lithium is a powerful phospholipase A2 (PLA2) inhibitor suggest that PLA2 activation, and subsequent cell signaling overactivation by increased fatty acid release may be the primary abnormality in bipolar affective disorder (BPAD), thus making PLA2 genes attractive candidates for the susceptibility to BPAD. The present study investigates polymorphisms in cytosolic phospholipase A2 (cPLA2), calcium-independent phospholipase A2 (iPLA2), and secretory phospholipase (sPLA2) genes in a Brazilian sample. METHODS: A cross-sectional study was performed with 181 unrelated DSM-IIIR BPAD subjects and 312 controls. A polymerase chain reaction-restriction fragment length polymorphism assay for BanI cPLA2 and AvrII iPLA2 polymorphisms was performed, and an ATT repeat in sPLA2 was assessed using a semiautomated genetic analyzer (ALFexpress). RESULTS: There was no significant difference observed in the allelic and genotypic distribution between the BPAD and control groups for cPLA2 (genotype: chi2 = 0.8, 2df, p = 0.6; allele chi2 = 0, 1df, p = 0.9), iPLA2 (genotype: chi2 = 1.7, 2df, p = 0.4; allele: chi2 = 0.3, 1df, p = 0.6), and sPLA2 (allele: chi2 = 3.6, 6df, p = 0.8). CONCLUSION: Our results failed to demonstrate that the studied PLA2 polymorphisms were associated with an increased risk for BPAD in our sample.

Association of a new polymorphism in ALOX12 gene with bipolar disorder.

Bipolar disorder (BPD) is characterised by episodes of excitement interspersed with periods of depression. The role of genetic factors in BPD is indicated by studies in monozygotic twins showing 40-70 % of concordance. Studies using genetic markers showed linkage of genes for affective disorders in different chromosome regions, emphasising the polygenic and multifactorial traits. The main goal of our research is to search non-synonymous SNPs (those that result in modifications in protein sequence) in genes that can be associated with psychiatric diseases as suggested by genomic mapping and/or by physiological function of the protein. Using DNA sequencing we could confirm a new non-synonymous SNP in the conservative domain of the ALOX12 gene (17p13.1), suggested by EST alignment. This SNP is an alteration from G to A that leads to a change of an arginine (A) to a glutamine in one of the most important domains of the protein. This SNP was evaluated by DNA sequencing in 182 patients with BPD and 160 control individuals. An increased presence of allele A among patients (60 % in controls and 73.1 % in cases; chi(2) = 6.581, P = 0.010; OR = 1.8095, 95 % CI = 1.1477-2.853) was found, suggesting an association of this polymorphism with the BPD in this Brazilian sample.