原发性高血压患者上皮钠通道1γ亚单位(SCNN1G)基因多态性与尿钠排泄及血压之间的关系

The relationship of polymorphism of the sodium channel epithelial 1 subunit gamma (SCNN1G) gene with urinary sodium excretion and blood pressure in patients with essential hypertension

  • 摘要:
    目的 分析原发性高血压患者上皮钠通道1γ亚单位(SCNN1G)基因的基因型及等位基因分布特点,探究此基因多态性与24 h尿钠排泄、血压的关系。
    方法 选择昆明医科大学附属延安医院2018年5月至2021年8月诊断为原发性高血压的患者511例,收集患者24 h尿电解质,对入组患者进行SCNN1G基因检测,用线性回归分析SCNN1G基因与血压、24 h尿钠的关系,用广义多因子降维法(GMDR)分析SCNN1G基因与环境的交互作用。
    结果 与SCNN1G基因rs4299163 WM基因型个体比较,MM基因型个体24 h尿钠排泄量较低(160.69±82.11)比(189.46±91.36)mmol,P<0.05。与SCNN1G基因rs4499238 WM基因型个体比较,MM基因型个体24 h尿钠排泄量较低(160.16±81.35)比(191.05±93.06)mmol,P<0.05。与SCNN1G基因rs5735 WW或WM基因型个体相比,MM基因型个体24 h尿钠排泄量较高(208.53±79.75)比(164.74±89.58)、(164.55±68.43)mmol,均P<0.05。SCNN1G基因各位点不同基因型患者24 h收缩压、白天收缩压、白天舒张压比较差异有统计学意义(P<0.05),夜间舒张压比较差异无统计学意义(P>0.05)。多元线性回归分析显示,性别(女性,B=−24.556,P=0.001)、体重指数 (B=2.639,P=0.013)、24 h尿钾(B=0.589,P<0.001)、SCNN1G基因rs5735位点(WM+MM,B=40.649,P=0.039)是24 h尿钠排泄的影响因素,性别、年龄、24 h尿钠是24 h收缩压、24 h舒张压的影响因素(P<0.05)。GMDR分析显示,由rs40739309、rs7404408、rs4299163、rs5735与环境因素(年龄、性别、体重指数)构建的交互作用模型和由rs40739309、rs7404408、rs4299163、rs4073291、rs5735与环境因素(年龄、性别、体重指数)构建的交互作用模型最佳(训练样本准确性、检验样本准确性及交叉验证一致性最佳)。
    结论 SCNN1G基因rs4299163、rs5735、rs4499238不同基因型与24 h尿钠排泄相关。SCNN1G基因各位点与环境存在交互作用,进而引起血压升高。

     

    Abstract:
    Objective To analyze the distribution characteristics of genotypes and alleles of the sodium channel epithelial 1 subunit gamma (SCNN1G) gene in patients with essential hypertension, and to investigate the relationship of these polymorphisms with 24-hour urinary sodium excretion and blood pressure.
    Methods A total of 511 patients diagnosed with essential hypertension at Yan'an Hospital Affiliated to Kunming Medical University between May 2018 and August 2021 were selected. Twenty-four-hour urinary electrolytes were collected from the patients, and SCNN1G gene was tested. Linear regression analysis was used to examine the relationship of the SCNN1G gene with blood pressure and 24-hour urinary sodium. Generalized multifactor dimensionality reduction (GMDR) method was used to analyze gene-environment interactions involving SCNN1G gene.
    Results Compared with individuals with the WM genotype of the SCNN1G gene rs4299163 locus, individuals with the MM genotype had a lower 24-hour urinary sodium excretion (160.69±82.11) vs (189.46±91.36) mmol, P<0.05. Compared with individuals with the WM genotype of the SCNN1G gene rs4499238 locus, individuals with the MM genotype had a lower 24-hour urinary sodium excretion (160.16±81.35) vs (191.05±93.06) mmol, P<0.05. Compared to individuals with the WW or WM genotype at the SCNN1G gene rs5735 locus, those with the MM genotype had significantly higher 24-hour urinary sodium excretion (208.53±79.75) vs (164.74±89.58), (164.55±68.43) mmol, respectively; both P<0.05. Statistically significant differences were observed in 24-hour systolic blood pressure (SBP), daytime SBP, and daytime diastolic blood pressure (DBP) among patients with different genotypes at the SCNN1G gene loci (P<0.05). However, no statistically significant difference was found in nighttime DBP (P>0.05). Multiple linear regression analysis revealed that gender (female, B=−24.556, P=0.001), body mass index (B=2.639, P=0.013), 24-hour urinary potassium excretion (B=0.589, P<0.001), and the SCNN1G gene rs5735 locus (WM+MM, B=40.649, P=0.039) were influencing factors for 24-hour urinary sodium excretion. Furthermore, gender, age, and 24-hour urinary sodium excretion were influencing factors for both 24-hour SBP and 24-hour DBP (P<0.05). GMDR analysis identified that the interaction models constructed from rs40739309, rs7404408, rs4299163, rs5735, and environmental factors (age, gender, body mass index), and constructed from rs40739309, rs7404408, rs4299163, rs4073291, rs5735, and environmental factors (age, gender, body mass index) were the optimal models, demonstrating the best training accuracy, testing accuracy, and cross-validation consistency.
    Conclusions Different genotypes at the SCNN1G rs4299163, rs5735, and rs4499238 loci are associated with 24-hour urinary sodium excretion. Interactions exist between various SCNN1G loci and environmental factors, which synergistically contribute to elevated blood pressure.

     

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