Contents lists available at ScienceDirect Gene Reports journal homepage: www.elsevier.com/locate/genrep Association of CDKAL1 gene rs7756992 A/G polymorphism with type 2 diabetes mellitus and diabetic nephropathy in the Egyptian population Ahmed A. El-Husseiny a,⁎ , Ayman M. Gamal El-Din a , Amr D. Mariee a , Ragaa R. Mohamed b , Amal H. Ibrahiem b a Biochemistry Department, College of Pharmacy, Al-Azhar University, Cairo, Egypt b Internal Medicine and Nephrology Department, El-Zahraa Hospital, Al-Azhar University, Cairo, Egypt ARTICLE INFO Keywords: Type 2 diabetes mellitus CDKAL1 Polymorphism Egyptian population ABSTRACT Objectives: Cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1 (CDKAL1) gene has been recognized as one of the type 2 diabetes mellitus (T2DM) associated genes by genome-wide association studies. Even though, the association of its rs7756992 A/G polymorphism varies in different ethnic populations. Therefore, this study was designed to evaluate the influence of single nucleotide polymorphism rs7756992 in CDKAL1 gene as a possible genetic predisposing factor for T2DM among Egyptian population. Furthermore, the association of rs7756992 variant with diabetic nephropathy as one of the most serious diabetic complications was also investigated. Design and methods: 105 Egyptian patients with T2DM and 53 apparently healthy controls were enrolled in this study. Patients were divided into 50 T2DM patients without nephropathy and 55 T2DM patients with nephropathy. Genotyping was performed using TaqMan® allelic discrimination assay. Results: Results of this study showed a significant association between the rs7756992 variant of CDKAL1 gene and the risk of T2DM under allelic, additive, dominant and recessive models. Moreover, this variant was found to be significantly associated with reduced risk of diabetic nephropathy under the only dominant model and one of the two additive models used. Conclusions: Findings of this study revealed that rs7756992 variant of CDKAL1 gene is considered as a strong candidate for T2DM susceptibility whereas it is not considered as a genetic risk factor for diabetic nephropathy among Egyptian patients with T2DM. 1. Introduction The prevalence of type 2 diabetes mellitus (T2DM) has reached an epidemic level, with about 400 million adult patients throughout the world (Ozanne et al., 2017). In Egypt, T2DM is a fast-growing health problem that affects almost 15.6% of all adults aged 20 to 79 years, with an annual death of about 86,478 (Hegazi et al., 2015). Genetic predisposition is an important factor in the etiology of T2DM and the susceptibility to diabetic nephropathy (Fan et al., 2016; Liu et al., 2016). Accordingly, finding out new genetic risk factor contributing to T2DM in different world inhabitants would provide a better under- standing of the disease, and would open the door for new treatment strategies. Genome-wide association studies (GWAS) have identified > 60 loci encoding up to 500 different genes which increase the risk of T2DM (Rao et al., 2016). Among these genes, the cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1 (CDKAL1) has been identified as one of the T2DM associated genes (Saxena et al., 2007; Scott et al., 2007; Steinthorsdottir et al., 2007). Human CDKAL1 gene is one of the T2DM associated genes but this association varies in different ethnic populations (Dehwah et al., 2010). Genetic variants of CDKAL1 are associated with either defect in proinsulin conversion (Kirchhoff et al., 2008; Haupt et al., 2009; Stančáková et al., 2009) or decreased insulin response upon glucose stimulation (Saxena et al., 2007; Steinthorsdottir et al., 2007; Ruchat et al., 2009; 'tHart et al., 2010). The CDKAL1 gene rs7756992 A/G polymorphism is associated with T2DM in many different populations (Steinthorsdottir et al., 2007; Cauchi et al., 2008; Tabara et al., 2009; Chistiakov et al., 2011; Cauchi http://dx.doi.org/10.1016/j.genrep.2017.04.003 Received 25 January 2017; Received in revised form 30 March 2017; Accepted 5 April 2017 ⁎ Corresponding author at: Biochemistry Department, College of Pharmacy, Al-Azhar University, P.O. Box 11231, Nasr City, Cairo, Egypt. E-mail address: ahmedhelal0084@gmail.com (A.A. El-Husseiny). Abbreviations: CDKAL1, cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1; GWAS, genome-wide association studies; SNP, single nucleotide polymorphism; T2DM, type 2 diabetes mellitus; FPG, fasting plasma glucose; ACR, albumin to creatinine ratio; HbA1c, hemoglobin A1c; MAF, minor allele frequency; OR, odds ratio; 95% CI, 95% confidence interval Gene Reports 7 (2017) 142–146 Available online 08 April 2017 2452-0144/ © 2017 Elsevier Inc. All rights reserved. MARK