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

•Copy number variation (CNV) study was performed to understand genomic variation in type 2 diabetes (T2D).•5 CNV loci are associated with the risk of T2D in a Korean population.•KCNIP1 containing CNV locus is related to insulin secretion in insulinoma cells.

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.