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白细胞介素 6 启动子多态性热点(-174G/C 和-572G/C)与心血管疾病危险因素的相关性。

Association of IL-6 promoter polymorphism hotspots (- 174G/C and - 572G/C) with cardiovascular disease risk factors.

机构信息

King Fahd Medical Research Center, King Abdulaziz University, Jeddah, P.O. Box 80216, Jeddah, 21589, Saudi Arabia.

Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, P.O. Box 80216, Jeddah, 21589, Saudi Arabia.

出版信息

Mol Biol Rep. 2022 Mar;49(3):2265-2272. doi: 10.1007/s11033-021-07048-8. Epub 2022 Jan 13.

DOI:10.1007/s11033-021-07048-8
PMID:35023009
Abstract

BACKGROUND

Cardiovascular disease (CVD) is the leading cause of death globally, despite the recent advancements in clinical research. Early diagnosis of CVD and prevention of future complications are important for the management of CVD. In the present study, we determined the genotypic linkage of interleukin-6 (IL-6) promoters with the clinical, biochemical, and inflammatory markers of CVD in the Saudi population.

MATERIALS AND METHODS

The study consisted of 89 patients (male and female) with CVD who were admitted at the King Abdulaziz university hospital, Jeddah, Saudi Arabia. The biochemical parameters were evaluated using an automated chemistry analyzer, and inflammatory markers were measured using specific enzyme-linked immunosorbent assay (ELISA) kits. For genotypic analysis, Sanger sequencing was performed. We observed a statistically significant association (p < 0.05) between GG (66.29%), GC (30.34%), and CC (3.37%) genotypes at the - 174G/C (rs1800795) hotspot and neopterin levels. However, the genotypes at the - 572G/C (rs1800796) hotspot did not show any association with age, gender, obesity, diabetes, hypertension, dyslipidemia, smoking, and coronary artery status. In addition, no significant association was observed with biochemical and inflammatory markers, namely fasting blood sugar, glycated hemoglobin A1c, creatinine, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, IL-6, and C-reactive protein. The comparison between different possible genotypic groups and CVD risk factors showed a statistically significant (p < 0.05) association between the male gender and HDL with GG, rs1800795 group vs. GC, rs1800796 group. Similarly, neopterin level was also found to be significantly (p < 0.05) associated with the genotypes GC, rs1800795, and GG, rs1800796. Additionally, the male gender (p < 0.01), age (p < 0.05), serum creatinine (p < 0.001), and neopterin (p < 0.05) were found to be significantly associated with GG, rs1800795 + GG, rs1800796, GC, rs1800795 + GC, and rs1800796 GC.

CONCLUSION

The direct association of neopterin level with IL-6 promoter polymorphism at - 174G/C (rs1800795) hotspot indicated the role of inflammation in CVD pathogenesis in the Saudi population.

摘要

背景

尽管临床研究取得了新进展,但心血管疾病 (CVD) 仍然是全球范围内的主要死亡原因。早期诊断 CVD 并预防未来并发症对于 CVD 的管理非常重要。在本研究中,我们确定了白细胞介素 6 (IL-6) 启动子与沙特人群 CVD 的临床、生化和炎症标志物的基因型连锁。

材料与方法

该研究包括 89 名(男性和女性)患有 CVD 的患者,他们在沙特阿拉伯吉达的阿卜杜勒阿齐兹国王大学医院就诊。使用自动化学分析仪评估生化参数,使用特定的酶联免疫吸附测定 (ELISA) 试剂盒测量炎症标志物。进行 Sanger 测序以进行基因分型分析。我们观察到 -174G/C(rs1800795)热点处 GG(66.29%)、GC(30.34%)和 CC(3.37%)基因型与新蝶呤水平之间存在统计学显著关联(p<0.05)。然而,-572G/C(rs1800796)热点处的基因型与年龄、性别、肥胖、糖尿病、高血压、血脂异常、吸烟和冠状动脉状况均无关联。此外,与生化和炎症标志物(即空腹血糖、糖化血红蛋白 A1c、肌酐、总胆固醇、甘油三酯、高密度脂蛋白胆固醇 (HDL-C)、低密度脂蛋白胆固醇、IL-6 和 C-反应蛋白)也无显著关联。不同可能的基因型组与 CVD 危险因素之间的比较显示,男性性别和 GG、rs1800795 组与 GC、rs1800796 组与 HDL 之间存在统计学显著(p<0.05)关联。同样,新蝶呤水平也与 GC、rs1800795 和 GG、rs1800796 基因型显著相关(p<0.05)。此外,男性性别(p<0.01)、年龄(p<0.05)、血清肌酐(p<0.001)和新蝶呤(p<0.05)与 GG、rs1800795+GG、rs1800796、GC、rs1800795+GC 和 rs1800796 GC 显著相关。

结论

新蝶呤水平与 IL-6 启动子-174G/C(rs1800795)热点多态性的直接关联表明炎症在沙特人群 CVD 发病机制中的作用。

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