Identification of interaction between serotonin transporter and glycogen synthase kinase-3 beta gene polymorphisms: role in susceptibility to bipolar disorder

被引：1

作者：

Subhashree, D. ^{[1
]}

Kumar, H. B. Kiran ^{[1
]}

Purushottam, Meera ^{[1
]}

Shubha, G. N. ^{[1
]}

Vallikiran, M. ^{[1
]}

Krishna, Nithin ^{[1
]}

Sriharsha, J. ^{[1
]}

Reddy, Y. C. J. ^{[1
,2
]}

Ghosh, Saurabh ^{[1
,3
]}

Mukherjee, Odity ^{[1
,4
]}

Jain, Sanjeev ^{[1
]}

机构：

[1] Natl Inst Mental Hlth & Adv Neurosci, Dept Psychiat, Mol Genet Lab, Hosur Rd, Bangalore 560029, Karnataka, India

[2] NIMHANS, Dept Psychiat, Bangalore, Karnataka, India

[3] Indian Stat Inst, Kolkata, W Bengal, India

[4] UAS, Natl Ctr Biol Sci, Bangalore, Karnataka, India

来源：

FUTURE NEUROLOGY | 2009年 / 4卷 / 03期

关键词：

5-HTTLPR; bipolar disorder; gene networks; GSK3B; multifactor dimensionality reduction;

D O I：

10.2217/FNL.09.11

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Genetic correlates of diseases of complex inheritance may include variations in several genes lying within a network of linked biological processes. Synaptic mechanisms, such as serotonin neurotransmission and second (third) messengers (e.g., glycogen synthase kinase [GSK]), have been implicated in susceptibility to mood disorders, the actions of therapeutic drugs and manipulation of circadian rhythms. A better understanding of such gene networks may be useful to understand the biology and treatment of mood disorders. Methods: We studied the association between serotonergic and GSK-mediated signaling networks with bipolar affective disorder (BPAD). We analyzed two single nucleotide polymorphisms (SNPs) in the HTR2A gene, a promoter SNP in SLC6A4 and a promoter SNP in the GSK3B gene in BPAD individuals and matched controls. A multifactor dimensionality reduction tool was employed to study gene-gene interactions and analyze multilocus genotype combination associations with high-or low-risk of BPAD. Results: Multifactor dimensionality reduction detected the best interacting model involving 5-HTTLPR (SLC6A4) and rs334558 (GSK3B). Conclusion: Our results suggest interplay between the serotonergic pathway and the second-messenger system involving GSK, which are important drug targets.

引用

页码：363 / 370

页数：8

共 35 条

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