齐齐哈尔地区汉族人群钠离子通道1A基因DNA甲基化与家族性原发性高血压的关系研究

Correlation between DNA methylation of SCNN1A gene and familial essential hypertension in Han population from Qiqihar

摘要:

目的 探究齐齐哈尔地区汉族人群钠离子通道1A（SCNN1A）基因DNA甲基化与家族性原发性高血压的关系。方法 选取2020年10月—2022年1月在齐齐哈尔市居住 ≥ 3代且年龄 > 18岁的汉族原发性高血压患者180例作为研究对象。根据高血压确诊时间将其分为初诊组（入组时新发高血压）和既往组（入组前已确诊高血压），每组90例。另选取该地区90例无高血压家族史的健康体检者作为对照组。收集并整理各组患者的临床基础资料，采用焦磷酸测序法检测SCNN1A基因DNA甲基化，比较各组患者的SCNN1A基因编码区CpG1～CpG6位点DNA甲基化，以多因素Logistic回归分析家族性原发性高血压的影响因素。结果 各组性别、年龄、BMI、吸烟史、饮酒史、LDL、TC及FBG比较，差异无统计学意义（P >0.05）。初诊组和既往组TG、UA高于对照组，HDL低于对照组（P <0.05）。各组SCNN1A基因编码区CpG3、CpG4、CpG5、CpG6位点甲基化比较，差异无统计学意义（P >0.05）。初诊组和既往组SCNN1A基因编码区CpG2位点甲基化低于对照组，既往组CpG1位点甲基化高于对照组（P <0.05）。多因素Logistic回归分析结果显示：HDL［O^R=5.078（95% CI：2.326，11.090）］及CpG2［O^R=6.322（95% CI：2.845，13.805）］位点甲基化降低，TG［O^R=4.486（95% CI：2.054，9.797）］、UA［O^R=5.557（95% CI：2.545，12.134）］及CpG1［O^R=5.463（95% CI：2.502，11.930）］位点甲基化升高是家族性原发性高血压的影响因素（P <0.05）。ROC曲线分析结果显示，CpG1、CpG2位点DNA甲基化单一及联合诊断家族性原发性高血压诊断的AUC分别为0.743（95% CI：0.621，0.865）、0.707（95% CI：0.612，0.841）和0.839（95% CI：0.753，0.925）。结论 齐齐哈尔地区汉族人群DNA甲基化与家族性原发性高血压关系密切，且SCNN1A基因CpG1位点甲基化存在升高趋势，CpG2位点甲基化存在降低趋势。

Abstract:

Objective To explore the correlation between DNA methylation of sodium channel epithelial 1 subunit alpha (SCNN1A) gene and familial essential hypertension in Han population from Qiqihar.Methods From October 2020 to January 2022, 180 patients of Han nationality with essential hypertension, who were older than 18 years and were at least the third generation living in Qiqihar, were enrolled as the subjects. According to the time of definite diagnosis of hypertension, they were divided into the initial diagnosis group (newly diagnosed as hypertension at the time of enrollment) and the established diagnosis group (confirmed as hypertension before the enrollment). Another 90 healthy people without family history of hypertension in this area were selected as the control group. The clinical data of the two groups were collected and sorted out. The DNA methylation level of SCNN1A gene was detected by pyrosequencing, and the DNA methylation level of CpG1-6 sites in the coding region of SCNN1A gene was compared among the groups. Factors affecting the occurrence of familial essential hypertension were analyzed by multivariable Logistic regression.Results There was no difference in the sex composition, age, body mass index (BMI), history of smoking, history of alcohol consumption, and the levels of low-density lipoprotein (LDL), total cholesterol (TC), and fasting blood glucose (FBG) among the groups (P > 0.05). Compared with the control group, levels of triglyceride (TG) and uric acid (UA) were higher and the level of high-density lipoprotein (HDL) was lower in the initial diagnosis group and the established diagnosis group (P < 0.05). The DNA methylation levels of CpG3-6 sites in the coding region of SCNN1A gene were not different among the groups (P > 0.05). The DNA methylation level of CpG2 sites in the coding region of SCNN1A gene of the initial diagnosis group and the established diagnosis group was lower than that of the control group (P < 0.05), while the DNA methylation level of CpG1 sites of the established diagnosis group was higher than that of the control group (P < 0.05). Multivariable Logistic regression analysis showed that the decreases in the level of HDL [ O^R = 5.078, (95% CI: 2.326, 11.090) ] and the DNA methylation level of CpG2 sites [O^R = 6.322, (95% CI: 2.845, 13.805) ], as well as the increases in the levels of TG [O^R = 4.486, (95% CI: 2.054, 9.797) ] and UA [O^R = 5.557, (95% CI: 2.545, 12.134) ] and the DNA methylation level of CpG1 sites [O^R = 5.463, (95% CI: 2.502, 11.930) ] were factors affecting the occurrence of familial essential hypertension (P < 0.05). The receiver operating characteristic (ROC) curve analysis revealed that the areas under the ROC curves (AUCs) of the DNA methylation levels of CpG1, CpG2 sites and their combination for diagnosing familial essential hypertension were 0.743 (95% CI: 0.621, 0.865), 0.707 (95% CI: 0.612, 0.841) and 0.839 (95% CI: 0.753, 0.925), respectively.Conclusions There is a close relationship between DNA methylation and familial essential hypertension in the Han population from Qiqihar. The methylation level of CpG1 sites of SCNN1A gene increases, while the methylation level of CpG2 sites of SCNN1A gene decreases in familial essential hypertension.