Association of GLP-1R Gene Polymorphisms with the risk of Dyslipidemia in Palestinian Patients with Type 2 Diabetes Mellitus
Date
2024-07-11
Authors
Maha Rashad Joma AlSharabati
مها رشاد جمعة الشرباتي
Journal Title
Journal ISSN
Volume Title
Publisher
Al-Quds University
Abstract
The high risk of cardiovascular events in diabetic patients is associated with dyslipidemia, a common concomitant disease of diabetes. Dyslipidemia comprises of a wide range of lipid disorders including over production of lipids or its deficiency. It is characterized by the presence of either elevated low density lipoprotein cholesterol (LDL-C) or elevated high total cholesterol (Hypercholesterolemia) or elevated triglycerides (Hypertriglyceridemia) or decreased high density lipoprotein cholesterol (HDL-C). Several studies have found that dyslipidemia can be associated by single nucleotide variations in specific genes. Therefore, the present study aimed to investigate GLP-1R gene polymorphisms rs10305420 and rs3765467 and its association with the risk of dyslipidemia in Palestinian patients with type 2 diabetes mellitus (T2DM). A cross sectional study was conducted between October 2023 and February 2024 at Jericho health center MOH. Herein, we used next generation sequencing (NGS) to study two single nucleotide polymorphisms (SNPs), rs10305420 and rs3765467 within the GLP-1R gene in one multiplex PCR tube. Bioinformatics analysis was done using free online galaxy program (https://usegalaxy.org.au/). A total of 216 T2DM patients were enrolled in this study and divided into two groups: The control group (patients without dyslipidemia) and case group (patients with dyslipidemia). The control group included patients aged 40 years or older with confirmed T2DM (diagnosed according to WHO criteria) and had no history of dyslipidemia (TC < 200 mg/dl, TG < 150 mg/dl, and no use of lipid‐lowering agents), while the case group included patients who aged 40 years or older with confirmed T2DM and dyslipidemia. Dyslipidemia was
defined by TC ≥ 240 mg/dl and/or TG ≥ 150 mg/dl, LDL-C ≥ 140 mg/dl, HDL-C < 40 mg/dl, and/or use of lipid‐lowering drugs. Participants under 40 years old, individuals with confirmed diagnosis of Type 1 Diabetes Mellitus, patients with incomplete medical records, patients with severe comorbidities (e.g., severe liver disease or cancer), and pregnant women were excluded from the study. The results showed higher rates of diabetic neuropathy, retinopathy, and hypertension among patients with dyslipidemia compared to those without dyslipidemia (p < 0.05). However, no statistically significant differences were observed in the prevalence of nephropathy, diabetic foot, or tobacco smoking status between the two groups, whereas female patients were more prevalent in the dyslipidemia group (p = 0.04). The genotype distributions of rs10305420 in the studied groups showed that the most frequent genotype in the dyslipidemia group was CC (27.8%), followed by CT (15.3%) and TT (7.9%). For those without dyslipidemia, the CC, CT, and TT genotypes were 26.4%, 17.6%, and 5.1%, respectively. The study showed no significant difference in the distribution of the rs10305420 genotype between the T2DM patients with and without dyslipidemia. For the second SNP, the GLP-1R rs3765467 polymorphism, almost all samples exhibited the GG genotype. The mean (TC, TG, and LDL) of T2DM patients with dyslipidemia were respectively higher than those without dyslipidemia (178.7± 39.2 vs. 155.5 ± 33.6, p < 0.001), (189.1 ± 140.1 vs. 106.7 ± 40.6, p < 0.001), and (103.1 ± 32.3 vs. 92.9 ± 27.6, p < 0.015). Mean age, BMI, systolic blood presure of T2DM patients with dyslipidemia were higher than those without dyslipidemia. In conclusion, the rs10305420 and rs3765467 polymorphisms in the GLP-1R gene were not
significantly associate with dyslipidemia in this population. Further studies with larger sample sizes are needed to confirm these findings.