1. Risk allele of gene variant rs6584389 is associated with increased intima-media thickness in patients with type 2 diabetes.
- Author
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Kozarova M, Malachovska Z, Zidzik J, Javorsky M, Demkova K, Habalova V, and Tkac I
- Subjects
- Age Factors, Aged, Asymptomatic Diseases, Biomarkers blood, Carotid Artery Diseases diagnostic imaging, Chi-Square Distribution, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 diagnosis, Diabetic Angiopathies diagnostic imaging, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Glycated Hemoglobin metabolism, Humans, Linear Models, Male, Middle Aged, PAX2 Transcription Factor genetics, Peripheral Arterial Disease diagnostic imaging, Phenotype, Pulse Wave Analysis, Risk Factors, Carotid Artery Diseases genetics, Carotid Intima-Media Thickness, Chromosomes, Human, Pair 10, Diabetes Mellitus, Type 2 genetics, Diabetic Angiopathies genetics, Peripheral Arterial Disease genetics, Polymorphism, Single Nucleotide
- Abstract
Background: Genome-wide association studies identified several gene variants associated with peripheral arterial disease (PAD). Among them, rs6584389 A>C was significantly associated with PAD defined by decreased ankle-brachial index (ABI). The aim of this study was to investigate whether the rs6584389 variant is also associated with the earlier stages of atherosclerosis assessed by intima-media thickness (IMT) or pulse-wave velocity (PWV) in clinically asymptomatic subjects with type 2 diabetes (T2DM), a group of patients with a high cardiovascular risk., Patients and Methods: In total, 111 patients with T2DM (56 females, 55 males) with a mean age 63.0 ± 9.1 years were consecutively included in the study. IMT was measured by ultrasound using 7 MHz linear transducer. PWV was measured using a piezoelectric method. Genotyping for rs6584389 was performed by PCR-HRMA method., Results: The carriers of the risk C-allele of rs6584389 variant had significantly higher mean left-side IMT (AA: 0.67 ± 0.12, AC 0.77 ± 0.21, CC 0.78 ± 0.22 mm; p = 0.04). In multiple linear regression analysis, rs6586389 genotype was significantly associated with all measured IMT parameters. The presence of each risk C-allele predicted an increase in left-side IMT by 0.056 mm (p = 0.017), right-side IMT by 0.053 mm (p = 0.039), average IMT by 0.054 mm (p = 0.023), and maximal IMT by 0.058 mm (p = 0.021). Age and HbA1c levels were also significantly associated with increased IMT in all multivariate models., Conclusions: Gene variant rs6584389 A>C near to PAX2 gene was associated with increased carotid IMT in patients with type 2 diabetes independently of the other main risk factors for atherosclerosis.
- Published
- 2018
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