期刊
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
卷 141B, 期 1, 页码 36-43出版社
WILEY
DOI: 10.1002/ajmg.b.30239
关键词
intracellular calcium homeostasis; calcium permeable channel; single nucleotide polymorphisms (SNPs); haplotype
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 < 7.0 x 10(-5); odds ratio (OR) = 2.60), and when stratified into BD-I (P < 7.0 x 10(-5), OR = 2.48) and BD-II (P = 7.0 x 10(-5), OR=2.88) subgroups. In addition, the alleles of the individual SNPs forming a seven marker at-risk haplotype were in excess in BD (12.0% in BD vs. 0.9% in controls; P=2.3 x 10(-12)). A weak relationship was also detected between BLCL [Ca2+](B) and TRPM2 SNP rs1612472 in intron 19. These findings suggest genetic variants of the TRPM2 gene increase risk for BD and support the notion that TRPM2 may be involved in the pathophysiology of BD. (C) 2005 Wiley-Liss, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据