A Novel SERPINB1 Single-Nucleotide Polymorphism Associated With Glycemic Control and β-Cell Function in Egyptian Type 2 Diabetic Patients.

Ghada H Sayed,Dina H Kassem,Aya Adel,Mohamed M Kamal

doi:10.3389/fendo.2020.00450

Ghada H Sayed, Dina H Kassem + Show 2 more

Open Access

https://doi.org/10.3389/fendo.2020.00450

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Abstract

Aims: Serine protease inhibitor B1 (SerpinB1) is a neutrophil elastase inhibitor that has been proved to be associated with type 2 diabetes mellitus and pancreatic β-cell proliferation. In this study, we investigated 2 SERPINB1 SNPs, rs114597282 and rs15286, regarding their association with diabetes risk and various anthropometric and biochemical parameters in Egyptian type 2 diabetic patients.Materials and Methods: A total of 160 subjects (62 control and 98 type 2 diabetic patients) participated in this study. Various anthropometric and biochemical parameters were assessed. Genotyping assay for the two SNPs was done using TaqMan genotyping assays. The association of rs15286 variants with risk of diabetes, various biochemical parameters, and glycemic control in diabetic patients was assessed.Results: All genotyped subjects were found to be homozygous TT for SERPINB1 rs114597282. All genotype variants of SERPINB1 rs15286 were found in our Egyptian subjects with A being the minor allele. The SNP rs15286 was not found to be associated with risk of diabetes. The AA genotype was found to be associated with lower fasting plasma glucose, lower HbA1c%, and better β-cell function and glycemic control in diabetic patients. The G allele was associated with poor glycemic control.Conclusions: The genotypes AA, AG, and GG of SERPINB1 gene SNP rs15286 are all represented in the studied sample; however, it is not associated with risk of diabetes. Genotype AA of SNP rs15286 is associated with better glycemic control and better β-cell function in diabetic patients, while the G allele potentially represents the “risk allele” of poor glycemic control.

Highlights

Diabetes mellitus (DM) is a complex multifaceted metabolic disorder
This study was approved by the ethical committee of the National Institute of Diabetes and Endocrinology—General Organization for Teaching Hospitals and Institutes (NIDE—GOTHI) under number IDE00203, and informed consent was obtained from every enrolled subject
fasting plasma glucose (FPG), HbA1C%, and lipid profile including TG, total cholesterol (TC), Low-density lipoprotein cholesterol (LDL-C), and even LDL-C/high-density lipoproteincholesterol (HDL-C) and TC/HDL-C were all significantly elevated in type 2 DM as compared to the control group

Summary

Introduction

Diabetes mellitus (DM) is a complex multifaceted metabolic disorder. The number of people suffering DM globally has risen from about 108 million in 1980 to nearly 422 million in 2014 [2], with a further expected increase to about 630 million people worldwide. Type 2 DM is the most common type of DM, and genetic-predisposition accounts for nearly 60–90% of the susceptibility to its development [3]. During the natural course of the disease, insulin resistance and β-cell loss or dysfunction are potential drivers for the various metabolic abnormalities associated with type 2 DM [3, 4]. When the functional insulinsecreting β-cell mass is compromised, the normal physiological glucose homeostasis is disrupted and type 2 DM manifests [5]

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