Association of the putative susceptibility gene, transient receptor potential protein melastatin type 2, with bipolar disorder

Disturbed intracellular calcium (Ca2+) homeostasis has been implicated in bipolar disorder (BD). Reduced mRNA levels of the transient receptor potential Ca2+ permeable channel melastatin type 2, TRPM2, in B lymphoblast cell lines (BLCL) from bipolar I disorder (BD‐I) patients showing elevated basal intracellular Ca2+ ([Ca2+]B), an index of altered intracellular Ca2+ homeostasis, along with its location within a putative BD susceptibility locus (21q22.3), implicates the involvement of this gene in the Ca2+ abnormalities and the genetic diathesis to BD. We tested this hypothesis by examining the association of selected single nucleotide polymorphisms (SNPs) and their haplotypes, spanning the TRPM2 gene, with BD and BLCL [Ca2+]B, in a case control design. The 5′ TaqMan SNP assay was used to detect selected SNPs. BLCL [Ca2+]B was determined by ratiometric fluorometry. SNP rs1618355 in intron 18 was significantly associated with BD as a whole (P