The Relationship of Polymorphism of the Sodium Channel Epithelial 1 Subunit Gamma ( <i>SCNN1G</i> ) Gene With Urinary Sodium Excretion and Blood Pressure in Patients With Essential Hypertension

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 between these polymorphisms and 24-hour urinary sodium (24h-UNa) 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 the SCNN1G gene was tested. Linear regression analysis was used to examine the relationship between the SCNN1G gene and blood pressure/24h-UNa. The generalized multifactor dimensionality reduction (GMDR) method was used to analyze gene–environment interactions involving the SCNN1G gene. RESULTS Compared with individuals with the WM genotype of the SCNN1G gene rs4299163 locus, individuals with the MM genotype had a lower 24h-UNa excretion ([160.69 ± 82.11] vs. [189.46 ± 91.36] mmol, P &amp;lt; 0.05). Compared with individuals with the WM genotype of the SCNN1G gene rs4499238 locus, individuals with the MM genotype had a lower 24h-UNa excretion ([160.16 ± 81.35] vs. [191.05 ± 93.06] mmol, P &amp;lt; 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 24h-UNa excretion ([208.53 ± 79.75] vs. [164.74 ± 89.58], [164.55 ± 68.43] mmol, respectively; both P &amp;lt; 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&amp;lt; 0.05). However, no statistically significant difference was found in nighttime DBP (P &amp;gt; 0.05). Multiple linear regression analysis revealed that gender (B = −24.556, P = 0.001), body mass index (B = 2.639, P = 0.013), 24-hour urinary potassium excretion (B = 0.589, P&amp;lt;0.001), and the SCNN1G gene rs5735 locus (B = 40.649, P = 0.039) were influencing factors for 24h-UNa excretion. Furthermore, gender, age, and 24h-UNa excretion were influencing factors for both 24-hour SBP and 24-hour DBP (P &amp;lt; 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 24h-UNa excretion. Interactions exist between various SCNN1G loci and environmental factors, which synergistically contribute to elevated blood pressure.