Genome-wide copy number variation study reveals KCNIP1 as a modulator of insulin secretion.
Genomics
; 104(2): 113-20, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24886904
ABSTRACT
Copy number variations (CNVs) have emerged as another important genetic marker in addition to SNP for understanding etiology of complex diseases. In light of this, we performed a genome-wide CNV study to identify type 2 diabetes (T2D)-associated CNV using an array comparative genomic hybridization from 3180 subjects for T2D cases (n=863) and controls (n=2,317). Thus, five CNV regions having a p-value threshold ≤0.05 were identified and evaluated by validation with quantitative PCR and comparison with previously reported CNV regions in the Database of Genomic Variants. Furthermore, we performed a functional experiment to assess the biological significance of a gene encompassing a CNV region. The inhibition of KCNIP1 led to increased insulin secretion in a glucose-dependent manner, but had no effect on insulin gene transcription as well as cell apoptosis. Taken together, these data indicate that KCNIP1 from CNV study might function as a T2D-susceptibility gene whose dysregulation alters insulin production.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Interatuantes com Canais de Kv
/
Variações do Número de Cópias de DNA
/
Insulina
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Genomics
Assunto da revista:
GENETICA
Ano de publicação:
2014
Tipo de documento:
Article