基因变异及心血管危险因素与单核细胞分泌白细胞介素6和10的关系

北京大学学报（医学版） ›› 2014, Vol. 46 ›› Issue (4): 589-595.

基因变异及心血管危险因素与单核细胞分泌白细胞介素6和10的关系

谢高强1△，于晖2，陈敬洲2，赵连成3△，任福秀4，史平4，武阳丰1,5,6

［1. 北京大学临床研究所，北京100191；2. 中国医学科学院，北京协和医学院，国家心血管病中心，阜外心血管病医院，心血管疾病国家重点实验室，心血管病基因研究室(中德实验室)，北京100037；3. 中国医学科学院，北京协和医学院，国家心血管病中心，阜外心血管病医院防治网络部，北京100037；4. 北京市石景山区疾病预防控制中心，北京100043；5. 北京大学公共卫生学院流行病与卫生统计学系，北京100191；6. 北京大学医学部乔治健康研究所，北京100191］

出版日期:2014-08-18 发布日期:2014-08-18

Relationship of genetic variants and cardiovascular risk factors with interleukin-6 and interleukin-10 secreted by monocytes

XIE Gao-qiang1△, YU Hui2, CHEN Jing-zhou2, ZHAO Lian-cheng3△, REN Fu-xiu4, SHI Ping4, WU Yang-feng1,5,6

(1. Peking University Clinical Research Institute, Beijing 100191, China; 2. SinoGerman Laboratory for Molecular Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China; 3. Department of Prevention Network, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China; 4. Shijingshan Center for Disease Control and Prevention, Beijing 100043, China; 5. Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China; 6. The George Institute, Peking University Health Science Center, Beijing 100191, China)

Online:2014-08-18 Published:2014-08-18

摘要/Abstract

摘要： 目的：研究白细胞介素（interleukin，IL）-6、IL-10基因变异及心血管危险因素［包括氧化低密度脂蛋白（oxygenized low density lipoprotein, ox-LDL）、缺乏体力活动、超重等］与单核细胞分泌IL-6和IL-10的关系。方法：2010年在北京社区人群随机抽取无心肌梗死和脑卒中病史的40名51~80岁的健康人，收集吸烟、饮酒资料，测量血压、空腹血糖、血脂等心血管危险因素指标，并检测IL-6（rs1800796、rs1524107、rs2066992）、IL-10基因变异（rs1800872、rs1554286、rs3021094）。分离静脉血单核细胞，在RPMI 1640培养液中培养24 h，分为二等份，一份加入ox-LDL(50 mg/L)刺激，另一份加入磷酸盐缓冲液(PBS)对照，继续培养48 h，采用ELISA法检测上清液IL-6和IL-10的浓度。结果：配对Wilcoxon检验显示，与PBS培养液相比，ox-LDL培养液中单核细胞分泌IL-6、IL-10以及IL-6/IL-10显著升高（P<0.01）。以PBS和ox-LDL培养液中IL浓度作为重复测量结果，调整年龄、性别后，重复测量的多因素一般线性模型显示，超重者（BMI≥26 kg/m2）单核细胞分泌IL-10显著低于体重较轻者（P=0.007），IL-6/IL-10则显著高于体重较低者（P=0.003）；缺乏体力活动者［metabolic equivalent of energy, METS<166 kJ/(kg·d)］单核细胞分泌的IL-6/IL-10显著高于体力活动较高者（P=0.046）；饮酒者单核细胞分泌的IL-6和IL-10显著高于不饮酒者（P=0.049和0.006）；高密度脂蛋白胆固醇（high-density lipoprotein-cholesterol, HDL-c）较高者(≥56.4 mg/dL)单核细胞分泌IL-6显著升高（P=0.027）；IL-10的3个单核苷酸多态性(single nucleotide polymorphism，SNP)位点(rs1800872、rs1554286、rs3021094)与ox-LDL对单核细胞分泌IL-10存在显著交互作用（P<0.05），IL-6基因SNP与ox-LDL无显著交互作用。结论：ox-LDL、缺乏体力活动、超重等心血管因素与炎症-抗炎平衡向炎症方向偏斜密切相关，IL-10基因和ox-LDL的交互作用与抗炎细胞因子IL-10表达密切相关。

关键词: 白细胞介素-6, 白细胞介素-10, 变异（遗传学）, 运动活动, 超重

Abstract: Objective：To examine the relationship of interleukin (IL)6 and IL10 genetic variants and cardiovascular factors ［oxygenized low density lipoprotein (oxLDL), lower physical activity, overweight, etc.］ with IL6 and IL10 secreted by monocytes. Methods: In the study, 40 health persons, aged from 51 to 80 years, without stroke and myocardial infarction, were randomly sampled from a communitybased population in Beijing in 2010. Their data on smoking, drinking, blood pressure, fasting glucose, and lipid were collected. The single nucleotide polymorphisms (SNPs) of IL6 (rs1800796, rs1524107, rs2066992) and IL10 (rs1800872, rs1554286, rs3021094) were genotyped. The human monocytes were cultivated in RPMI 1640 medium for 24 h; then divided into two equal parts, in which oxLDL (50 mg/L) and phosphate buffer solution (PBS) were added for another 48 h. Finally, the secretions of IL6 and IL10 in the culture supernatants were measured with ELISA. Results: Paired Wilcoxon tests showed that the IL6, IL10, and IL6/IL10 were significantly higher in oxLDL medium than in PBS one (all P<0.01). The concentrations in PBS/oxLDL taken as repeated measurements, and adjusted for age and gender, the repeated general linear models showed: IL10 was significantly lower for those overweight (BMI≥26 kg/m2) than for those normal weight (P=0.007), and IL6/IL10 was significantly higher in those overweight (P=0.003). The IL6/IL10 was significantly higher in those with lower physical activity ［metabolic equivalent of energy, METS<166 kJ/(kg·d)］ than those with higher physical activities (P=0.046). IL6 and IL10 were significantly higher in alcohol drinkers (P=0.049 and P=0.006). IL6 was significantly higher in those with higher highdensity lipoproteincholesterol (HDLc, ≥56.4 mg/dL, P=0.027). There were significant interactions between IL10 SNPs and oxLDL on IL10 (all P<0.05), but no significant interactions between IL6 gene SNPs and oxLDL on IL6. Conclusion: The oxLDL together with lower physical activity and overweight shifts the balance of proinflammatory and antiinflammatory in the direction of proinflammatory. The interaction between IL10 gene and oxLDL is intensively correlated with the secretion of the antiinflammatory cytokine IL10.

Key words: Interleukin6, Interleukin10, Variation (genetics), Motor activity, Overweight

谢高强1△, 于晖2, 陈敬洲2, 赵连成3△, 任福秀4, 史平4, 武阳丰1, 5, 6. 基因变异及心血管危险因素与单核细胞分泌白细胞介素6和10的关系[J]. 北京大学学报（医学版）, 2014, 46(4): 589-595.

XIE Gao-Qiang-1△, YU Hui-2, CHEN Jing-Zhou-2, ZHAO Lian-Cheng-3△, REN Fu-Xiu-4, SHI Ping-4, WU Yang-Feng-1, 5 , 6 . Relationship of genetic variants and cardiovascular risk factors with interleukin-6 and interleukin-10 secreted by monocytes[J]. Journal of Peking University(Health Sciences), 2014, 46(4): 589-595.

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