مقالات پذیرفته شده در هفتمین کنگره بین المللی زیست پزشکی
The LDLR rs2228671 CC genotype is associated with lower BMI in men with diabetes mellitus
The LDLR rs2228671 CC genotype is associated with lower BMI in men with diabetes mellitus
Afsaneh Zare,1Pegah Pourzargham,2 Atefe Ghamar Talepoor,3,* Mehrnoosh Doroudchi,4
1. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran 2. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran 3. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran 4. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Introduction: Type 2 Diabetes Mellitus (T2DM) is a chronic and age–related inflammatory disease. Although cardiovascular complications in patients with DM are common, the exact relation between DM and Cardiovascular Diseases is still unknown. LDL receptor (LDLR) is responsible for regulating plasma LDL-cholesterol concentrations and can associate with Insulin receptor on the cell membrane. This binding decreases the LDL particle clearance and can be modulated by the insulin level. Among LDLR polymorphisms, rs2228671 single nucleotide polymorphism (SNP) (C>T) has shown the strongest association with LDL-cholesterol level. In this study we evaluated the genetic link between LDLR and progression of atherosclerosis in diabetic and non-diabetic individuals.
Methods: Our study was conducted on 485 individuals who resided in Fars province of Iran. Based on the Diagnostic Angiography, patients were categorized to diabetes+angio+ (n=63), diabetes+angio- (n=48), and diabetes-angio+ (n=118) groups. Also 256 healthy blood donors were recruited and considered as control group (diabetes-angio-). DNA was extracted from peripheral blood by salting out method and LDLR gene polymorphism was detected by RFLP- PCR.
Results: We did not observe any significant difference in LDLR rs2228671 genotypes and alleles between the four groups. However, comparison of the 3 patients’ groups by regression analysis showed that CC genotype was increased significantly in men who had BMI lower than 25 (P=0.043). Accordingly, the frequencies of men and women with BMI<25 and CC genotype were 80% and 20%, respectively. While the frequencies of men and women with BMI>25 and CC genotype were 57.6% and 42.4%, respectively. There was also a significant difference between the 3 patients groups based on smoking status (P=0.005), gender (P=0.003) and blood pressure (P=0.001). Only 10.3% of smokers were diabetes+angio+, but 79.5% of smokers were diabetes-angio+. While 47.8% of female patients were diabetes+angio+, 67.9% of male patients were diabetes-angio+. Of those patients who had hypertension 45.9% were diabetes+angio+ while 76.8% of those without hypertension were diabetes-angio+.
Conclusion: We suggest that genetic variations in LDL clearance pathways may affect the progression of atherosclerosis in diabetic patients. The association of CC genotype with lower BMI may also have a protective role against diabetes in men. Also, hypertension plays a more significant role than smoking in progression of atherosclerosis in diabetic patients.