Association between the rs2279238 of the Liver X receptor alpha gene polymorphism and advanced carotid atherosclerosis in the Slovenian cohort.

BACKGROUND: Liver X receptor alpha (LXRA) plays important role in cholesterol and lipid homeostasis and lipid metabolism; moreover, it has been investigated as a candidate gene in a number of conditions, including onset and progression of atherosclerosis. We hypothesized that the LXRA gene rs2279238 polymorphism may be associated with the onset and progression of carotid atherosclerosis in the Slovenian cohort. METHODS: 783 unrelated Slovenian patients were included in this cross-sectional case-control study: 308 patients in the group of cases with severe internal carotid artery (ICA) stenosis (>75 %) and 475 patients with hemodynamically insignificant ICA stenosis (<50 %) in the control group. Medical records were used to acquire patient laboratory and clinical data. The TaqMan SNP Genotyping assay was used to genotype the rs2279238 polymorphism. RESULTS: Between the case and control groups, we identified a statistically significant variation in genotype distribution (p = 0.04), but not in allele frequency (p = 0.13) of the LXRA gene polymorphism rs2279238. The results, also show that there is a statistically significant association (p = 0.04) between the two genetic models (codominant and recessive) of the LXRA gene rs2279238 polymorphism and carotid atherosclerosis. CONCLUSION: In the Slovenian cohort, we found a significant association between the TT genotype of rs2279238 and advanced carotid artery disease, suggesting that this polymorphism might be a genetic risk factor for ICA atherosclerosis.

Association between rs2107595 HDAC9 gene polymorphism and advanced carotid atherosclerosis in the Slovenian cohort.

BACKGROUND: Histone deacetylase 9 (HDAC9) plays an important role in transcriptional regulation, cell cycle progression and developmental events; moreover, it has been investigated as a candidate gene in a number of conditions, including the onset and progression of atherosclerosis. We hypothesized that the rs2107595 HDAC9 gene polymorphism may be associated with advanced carotid artery disease in a Slovenian cohort. We also investigated the effect of this polymorphism on HDAC9 receptor expression in the internal carotid artery (ICA) specimens obtained by endarterectomy. METHODS: This case-control study enrolled 619 unrelated Slovenian patients: 311 patients with ICA stenosis > 75% as the study group and 308 patients with ICA stenosis < 50% as the control group. Patient laboratory and clinical data were obtained from the medical records. The rs2107595 polymorphisms were genotyped using TaqMan SNP Genotyping assay. HDAC9 expression was assessed by immunohistochemistry in 30 ICA specimens from patients with ICA atherosclerosis > 75%, and the numerical areal density of HDAC9 positive cells was calculated. RESULTS: The occurrence of advanced ICA atherosclerosis in the Slovenian cohort was 3.81 times higher in the codominant genetic model (OR = 3.81, 95%CI = 1.06-13.77, p = 0.04), and 3.10 times higher in the recessive genetic model (OR = 3.10, 95%CI = 1.16-8.27, p = 0.02). In addition, the A allele of rs2107595 was associated with increased HDAC9 expression in the ICA specimens obtained by endarterectomy. CONCLUSIONS: We observed a significant association between the AA genotype of rs2107595 with the advanced carotid artery disease in our Slovenian cohort, indicating that this polymorphism may be a genetic risk factor for ICA atherosclerosis.