Suggestive evidence for association between L-type voltage-gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in latinos: a family-based association study
artículo original
Fecha
2013-02-25Autor
Xu, Chun
Zavala, Juan Manuel
Armas, Regina
Contreras, Salvador
Dassori, Albana
Ontiveros Sánchez de la Barquera, Jose Alfonso
Nicolini Sánchez, José Humberto
Escamilla, Michael
Ramírez, Mercedes
Flores, Deborah
Jerez, Álvaro
Raventós Vorst, Henriette
González, Suzanne
Leach, Robin J.
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Objectives: Through recent genome-wide association studies (GWASs),
several groups have reported significant association between variants in
the calcium channel, voltage-dependent, L-type, alpha 1C subunit
(CACNA1C) and bipolar disorder (BP) in European and European-
American cohorts. We performed a family-based association study to
determine whether CACNA1C is associated with BP in the Latino
population.
Methods: This study included 913 individuals from 215 Latino
pedigrees recruited from the USA, Mexico, Guatemala, and Costa Rica.
The Illumina GoldenGate Genotyping Assay was used to genotype 58
single-nucleotide polymorphisms (SNPs) that spanned a 602.9-kb region
encompassing the CACNA1C gene including two SNPs (rs7297582 and
rs1006737) previously shown to associate with BP. Individual SNP and
haplotype association analyses were performed using Family-Based
Association Test (version 2.0.3) and Haploview (version 4.2) software.
Results: An eight-locus haplotype block that included these two
markers showed significant association with BP (global marker permuted
p = 0.0018) in the Latino population. For individual SNPs, this sample
had insufficient power (10%) to detect associations with SNPs with
minor effect (odds ratio = 1.15).
Conclusions: Although we were not able to replicate findings of
association between individual CACNA1C SNPs rs7297582 and
rs1006737 and BP, we were able to replicate the GWAS signal reported
for CACNA1C through a haplotype analysis that encompassed these
previously reported significant SNPs. These results provide additional
evidence that CACNA1C is associated with BP and provides the first
evidence that variations in this gene might play a role in the pathogenesis
of this disorder in the Latino population.
External link to the item
10.1111/bdi.12041
artículo -- Universidad de Costa Rica. Centro Investigación en Biología Molecular y Celular, 2013