The Association of Nucleobindin 2 Gene (NUCB2) Variants with Type 2 Diabetes Mellitus Among Iranian Azeri-Turkish Population

Soodabeh khalili^¹,2, Mahmoud Shekari Khaniani², Naser Aghamohammdzade³, Abolfazl Akbarzadeh⁴ and Sima Mansoori Derakhshan¹^,2*

¹Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

²Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

³Department of Internal Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

⁴Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

DOI : http://dx.doi.org/10.13005/bbra/2335

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 5′ UTR, exon1, and 5′ 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 5′ 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 five of the polymorphisms [rs 214088 (c.-406C >G), rs 4757506 (c.254A > G), rs369209853 (c.-205G > A), rs214087 (c.-166G > C), and rs373592192 (c.-281G > 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.

KEYWORDS: NUCB2; type 2 diabetes; Single nucleotide polymorphism

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