Divergent patterns of genic copy number variation in KCNIP1 gene reveal risk locus of type 2 diabetes in Chinese population.

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 Ca2+-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.

The Formation Mechanism of Hydrogels.

Hydrogels are degradable polymeric networks, in which cross-links play a vital role in structure formation and degradation. Cross-linking is a stabilization process in polymer chemistry that leads to the multi-dimensional extension of polymeric chains, resulting in network structures. By crosslinking, hydrogels are formed into stable structures that differ from their raw materials. Generally, hydrogels can be prepared from either synthetic or natural polymers. Based on the types of cross-link junctions, hydrogels can be categorized into two groups: the chemically cross-linked and the physically cross-linked. Chemically cross-linked gels have permanent junctions, in which covalent bonds are present between different polymer chains, thus leading to excellent mechanical strength. Although chemical cross-linking is a highly resourceful method for the formation of hydrogels, the cross-linkers used in hydrogel preparation should be extracted from the hydrogels before use, due to their reported toxicity, while, in physically cross-linked gels, dissolution is prevented by physical interactions, such as ionic interactions, hydrogen bonds or hydrophobic interactions. Physically cross-linked methods for the preparation of hydrogels are the alternative solution for cross-linker toxicity. Both methods will be discussed in this review.

CREB1 functional polymorphisms modulating promoter transcriptional activity are associated with type 2 diabetes mellitus risk in Chinese population.

The cAMP responsive element binding protein 1 (CREB1) is a ubiquitous transcription factor that contributes to the regulation of gluconeogenesis. The mechanisms of the CREB1 function remain largely unknown. In this study, we aimed to explore genetic variations in CREB1 promoter region and determine whether these loci affect transcriptional activity and risk on type 2 diabetes (T2D). Three polymorphisms were identified and designated as MU1, MU2 and MU3, respectively. Genotypic distribution analysis revealed that MU1 genotypes presented similar distribution between T2D and healthy controls (P > 0.05), while the MU2 and MU3 showed significant differences (P < 0.05). Haplotypic blocks of the three loci were constructed, and H1-TGA, H2-TTT and H3-ATT had higher frequencies in T2D patients than those in controls. Association studies revealed that the three loci significantly affected plasma glucose, glycated hemoglobin and insulin secretion. Disequilibrium analysis identified that the MU2 and MU3 variants were strongly linked in T2D (r2 = 0.348, D' = 1.0). Further analysis indicated that MU2 (TT vs GG, OR = 2.38, 95%CI = 1.19-4.77, P = 0.01) and MU3 (AA vs TT, OR = 1.16, 95%CI = 1.19-4.77, P = 0.04) were significantly associated with T2D in dominant genotypes. Luciferase assay showed that T-A haplotype from the highly linked MU2 and MU3 exhibited maximal promoter activity, which was consistent with the correlation results. We concluded that the TT genotype of MU2 and the AA genotype of MU3 could be used as molecular markers for evaluating the risk on T2D.