Genomics, 2014, 01, 113─120

Genome-wide copy number variation reveals KCNIP1 as a modulator of insulin secretion

Lee HS, Moon S, Kim YJ, Han BG, Kim JM, Kim BJ

Abstract

Copy number variations (CNVs) haveemerged as another important geneticmarker 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 validationwith quantitative PCR and comparisonwith 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 tranion 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

• ISBN or ISSN: 0888-7543

• 본 연구는 질병관리본부 연구개발과제(과제번호 2010-N73004-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2010-N73004-00) by Research of Korea Centers for Disease Control and Prevention.