title: Genome-wide copy number variation study reveals KCNIP1 as a modulator of insulin secretion.
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.
authors.affiliation: Center for Genome Science, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: Heun-Sik
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Center for Genome Science, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Moon
authors.affiliation: Center for Genome Science, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Yun
authors.affiliation: Center for Genome Science, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: MeeHee
authors.initials: M
authors.lastname: Lee
authors.affiliation: Center for Genome Science, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: Mi Yeong
authors.initials: MY
authors.lastname: Hwang
authors.affiliation: Center for Genome Science, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Center for Genome Science, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: Bok-Ghee
authors.initials: BG
authors.lastname: Han
authors.affiliation: Center for Genome Science, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea. Electronic address: goodmin@gmail.com.
authors.forename: Jeong-Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Center for Genome Science, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea. Electronic address: kbj6181@cdc.go.kr.
authors.forename: Bong-Jo
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002460:Cell Line; D002470:Cell Survival; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D055785:Gene Knockdown Techniques; D056426:Genetic Loci; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma / Q000235:genetics; D051605:Kv Channel-Interacting Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051381:Rats
chemical_list: D005819:Genetic Markers; D007328:Insulin; C496750:KCNIP1 protein, human; D051605:Kv Channel-Interacting Proteins
keywords: Association study; Copy number variation (CNV); Insulin secretion; KCNIP1; Type 2 diabetes