Relation of Rs12255372 (G/T) Polymorphisim in Transcription Factor 7 Like 2Gene with Betatrophin Level in Patients with Diabetes Mellitus Type 2

Abstract

Transcription Factor7-Like2 also known as TCF7L2 or TCF4 is a protein acting  as a transcription factor in human is encoded by the TCF7L2 gene. TCF7L2ʼs role in glucose metabolism is expressed in many tissues such as gut, brain, liver and skeletal muscle. However,TCF7L2 does not directly regulate glucose metabolism in β-cell, but regulate glucose metabolism in pancreatic and liver.

This study aims to examine the role of rs12255372 (G/T) single nucleotide polymorphism of TCF7L2 gene polymorphism on the susceptibility of type 2 of Diabetes Mellitus  (T2DM) patients, as well as  to investigate the role of betatrophin in T2DM pathogenesis  and to study the relation between rs12255372(G/T) polymorphism with betatrophin level in patients with T2DM and healthy control in Babylon Province.

The study was conducted from the period from November 2019 to July 2020. This case-control study include 90 subjects. 45 persons with T2DM patients and 45 healthy control. Venous blood samples five milliliters of sample was collected and divided into 2 parts: 2 ml in to EDTA tube for molecular study and HbA1c test, while another 3 ml put in a plain tube for collection of serum. The concentration of glucose, lipid profile, and HbA_1c was done by use a colorimetric methods. Determination of betatrophin was done by ELISA method in addition to the study of polymorphisms in TC7L2 gene by sequencing.

Serum level of glucose, HbA1c, cholesterol (TC) triglycerides, LDL-C, VLDL-C found to be significantly increased in patient when compared with healthy control. Whilst HDL-C and betatrophin level were found to be non-significantly changed in patients when compared with healthy control. TCF7L2 gene (rs12255372) polymorphism found to have three genotype (GG, GT, and TT) corresponding to the alleles G and T. The homozygote genotype of wild allele  showed a higher frequency in control  (75%) than in patients (12.5%), while the heterozygote genotype showed a higher frequency in patients (43.5%) than in control (25%) (p= 0.0001, odd ratio= 10.5 and C.I. were 14.0361 to 4864.7110). In another hand none of the control samples showed the TT genotype while patients showed (43.5%) frequency (p= 0.0002, odd ratio= 261. The TT genotype showed higher frequencies in patients than in control and it has a highly significant risk factor.