Divergent patterns of genic copy number variation in <i>KCNIP1</i> gene reveal risk locus of type 2 diabetes in Chinese population

Abstract

Abstract. Copy number variation (CNV) has emerged as another important genetic marker in addition to SNP for understanding etiology of complex disease. Kv channel interacting protein 1 (KCNIP1) is a Ca 2+ -dependent transcriptional modulator that contributes to the regulation of insulin secretion. Previous genome-wide CNV assay identified the KCNIP1 gene encompassing a CNV region, however, its further effect and risk rate on type 2 diabetes (T2D) have rarely been addressed, especially in Chinese population. The current study aims to detect and excavate genetic distribution profile of KCNIP1 CNV in Chinese T2D and control populations, and further to investigate the associations with clinical characteristics. Divergent patterns of the KCNIP1 CNV were identified (p < 0.01), in which the copy number gain was predominant in T2D, while the copy number normal accounted for the most in control group. Consistently, the individuals with copy number gain showed significant risk on T2D (OR = 4.550, p < 0.01). The KCNIP1 copy numbers presented significantly positive correlations with fasting plasma glucose and glycated hemoglobin in T2D. For OGTT test, the T2D patients with copy number gain had remarkably elevated glucose contents (60, 120, 180-min, p < 0.05 or p < 0.01) and diminished insulin levels (60, 120-min, p < 0.05) than those with copy number loss and normal, which suggested that the KCNIP1 CNV was correlated with the glucose and insulin action. This is the first CNV association study of the KCNIP1 gene in Chinese population, and these data indicated that KCNIP1 might function as a T2D-susceptibility gene whose dysregulation alters insulin production.

Exploring the Interactions between Human microRNAs and the Ilheus Virus Genome

“…Also associated with the 5 cap region in the ILHV genome, miRNA hsa-mir-4693, according to functional enrichment analysis, has been linked as a regulator of the targets KCNIP1 and ARRB2. Both of these targets are associated with the regulation of regulatory subunits of type A cellular potassium channels, which modulate the excitability of neuronal membranes, agonist-mediated desensitization of G protein-coupled receptors, and mediate the processes of desensitization and resensitization of cellular receptors to hormones, neurotransmitters, and immune signaling, respectively [22,23].…”

Ultra-performance liquid chromatography-mass spectrometry-based metabolomics reveals Huangqiliuyi decoction attenuates abnormal metabolism as a novel therapeutic opportunity for type 2 diabetes

“…Insulin resistance (IR) is dened by the WHO as a common ground for T2DM and various complications caused by it. 26,27 Currently, the "second strike" doctrine of oxidative stress has occupied the core position of IR research. Studies have shown that oxidative stress not only originates from IR, but also damages islet b cells and aggravates lipid metabolism disorder.…”

Quantitative evaluation of <i>PTPN22</i> copy number variation by digital droplet PCR and association with type 2 diabetes risk

“…1A and B, the copy numbers of the PTPN22 gene were detected by Exon7-probe1, Exon12-probe2, and Intron17-probe3, and the same tendency of the copy number variations was investigated between the T2D patients and controls. Furthermore, quantitative PCR (qPCR) method was used to confirm the copy number as described by our previous study [8]. The CN types were classified as gain (>0.5), loss (<-0.5) and normal (<| ±0.5|) based on the log 2 2 -ΔΔCt values.…”

“…CNVs also play important roles in modeling complex human diseases. Extensive CNVs evaluation studies have identified significant associations between CNVs and diseases such as schizophrenia [4], tumor [5,6], and endocrine metabolism disorders [7,8] using the candidategene approaches.…”

“…Grayson et al identified 39 CNVs presented different distribution (with enriched or depleted copy number) between diabetes and healthy controls using SNP array [12]. Subsequent studies have promulgated that some CNVs spanning with functional genes, such as exon-deletion in the AT-hook transcription factor (AKNA) domain containing 1 gene (AKNAD1) [13], the variable E2 region of the leptin receptor gene (LEPR) [14] as well as the Kv channel interacting protein 1 gene (KCNIP1) [8], were associated with glucose and insulin metabolism disorders. Therefore, CNVs may be considered as the promising molecular markers for the diagnosis and clinical therapy of T2D.…”