Association of Calcium Channel Gene Polymorphisms with Bipolar Disorder in a Taiwanese Sample
Date Issued
2011
Date
2011
Author(s)
Jan, Wen-Chi
Abstract
Objectives. Genetic variants in voltage-gated calcium channel (Cav) genes, CACNA1C and CACNB2, were reported to be associated with bipolar disorder (BPD) in recent genome-wide association studies. However, only a few Cav genes were identified in prior association studies. The current study aimed to first evaluate the associations between common variants in Cav gene family and BPD more extensively. We also performed analysis for multiple risk variants and to test interaction effects among different Cav genes that encode for subunits of calcium channel. Methods. A case-control association study for patients with BPD and healthy controls was conducted in Taiwan. We selected 7 Cav genes, including CACNA1S, CACNA1C, CACNA1E, CACNB2, CACNG1, CACNG2 and CACNG5, based on evidence in prior association studies and significant linkage regions for BPD. Genotyping for thirteen SNPs (single nucleotide polymorphisms) was performed using GoldenGate® VeraCodeTM assays in 280 BPD patients and 200 controls. We conducted both single marker and multi-loci association analyses. Pair-wise interactions among SNPs using allelic and genotypic models were tested using the Boolean operation based screening and testing. Results. The strongest association was observed for rs11013860 in CACNA1C and rs2284018 in CACNG2 gene with BPD. A dose response analysis of four markers (rs10848635, rs704326, rs11013860 and rs2284018) revealed high accumulative risk for increasing numbers of risk genotypes an individual endorsed (trend test P < 0.02). Suggestive interactions were found between genes encoded for different subunits of calcium channel, including CACNA1S-CACNA1E, CACNB2-CACNG2, CACNAB2-CACNG5, and CACNA1C-CACNG5. Conclusions. Lines of evidence from single marker, multi-loci, and interactions analyses revealed the associations between calcium channel genes and bipolar disorder. Our results suggested the involvement of
common genetic variants in calcium channel genes to confer the risk for developing bipolar disorder in an Asian population. Futher replication and basic research is needed to investigate the functional proerty of these genes to contribute on understanding etiological mechanism of bipolar illess.
Subjects
Bipolar disorder
calcium channels
genetic polymorphisms
interaction
Type
thesis
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