The association of nucleobindin 2 gene (NUCB2) variants with type 2 diabetes mellitus among Iranian Azeri-Turkish population

Abstract

Nesfatin-1, which is derived from the NEFA/nucleobindin 2 (NUCB2) precursor, is a satiety factor secreted by several tissues, including the hypothalamus. NUCB2 gene expression positively correlates with insulin secretory capacity, as well as with insulin and glucagon gene expression in human islets. Therefore, we hypothesized that polymorphisms in the NUCB2 gene promoter influence the susceptibility for the development of diabetes. In the current study, we investigated the association of NUCB2 polymorphisms in the promoter region and 52 UTR, exon1, and 52 part of intron 1 of NUCB2 gene with type II diabetes. A total of 200 patients with type II diabetes and 200 healthy controls subjects were enrolled in this study. The 52 part of NUCB2 variants was assessed using PCR and direct sequencing. Twelve variants, including rs186174(c.-427A > C), rs214088 (c.-406C > G), rs4757506(c.254A > G), rs369209853 (c.- 205G > A), rs214087 (c.-166G > C), rs373592192 (c.-281G > A), rs182903196 (c.-308G > A), rs 370538176 (c.- 426C > G), rs 190662423 (c.-612C > A), rs115148100 (c.-653G > A), rs374389403 (c -233T > c), and rs377756452 (c -207G > A), were identified. Analysis of the results showed that the frequency of seven of the polymorphisms [rs186174 (c.-427A > C), rs 4757506 (c.254A > G), rs369209853 (c.-205G > A), rs214087 (c.-166G > C), and rs182903196 (c.-308G > A)] is significantly different between patients and controls subjects (P < 0.05), which indicates the association of these polymorphisms with type 2 diabetes. Although the relationship between the promoter region of NUCB2 gene and T2D remains uncertain at present, These findings may support the role of NUCB2 gene in the regulation of the regulation of blood glucose and the increased type 2 diabetes in humans.