Genetic variation in salt taste receptors impact salt intake and blood pressure

**Background:** High dietary sodium consumption is a major contributor to cardiovascular disease (CVD) mortality, with approximately 1.7 million CVD deaths in 2010 attributed to high sodium intake. Both genetic and environmental factors influence sodium consumption and blood pressure (BP). Salt taste perception, mediated by amiloride-sensitive (ENaC protein) and amiloride-insensitive (TRPV1) fibers, may be influenced by genetic variations in taste receptor genes. Single nucleotide polymorphisms (SNPs) in SCNN1B (encoding ENaC β subunit) and TRPV1 genes have been associated with differences in salt taste perception and BP, but few studies have examined these associations in Middle Eastern populations. This study aimed to evaluate associations between SNPs in salt taste receptor genes with dietary salt intake and BP in Iranian adults.

**Methods:** A cross-sectional study was conducted among 116 randomly selected healthy adults aged ≥18 years in Isfahan, Iran. Exclusion criteria included diabetes, renal insufficiency, special dietary regimens, diuretic use, pregnancy, lactation, impaired taste, and incomplete 24-hour urine collection. Participants underwent sodium intake determination by 24-hour urine collection (mean of two samples) and dietary assessment using a validated 136-item semi-quantitative food frequency questionnaire (FFQ). BP was measured manually with a mercury sphygmomanometer according to standard protocols. Whole blood was collected for DNA extraction and genotyping of SNP rs239345 in SCNN1B and rs224534, rs4790151, and rs8065080 in TRPV1 using ARMS method. Statistical analysis used one-way ANOVA with Bonferroni post-hoc or Kruskal-Wallis tests as appropriate.

**Key Results:** The study included 116 participants (56% male, mean age 35.4±7.7 years, mean BMI 27.3±4.9 kg/m²). Mean 24-hour urinary sodium was 4651.0±1647.7 mg/day. For rs239345 (SCNN1B), sodium consumption was significantly higher in A-allele carriers (AA genotype: 4808.4±824.4 mg/day) compared to TT genotype (4043.5±989.3 mg/day; P=0.004). Diastolic BP was also significantly higher in AA genotype carriers (83.6±8.5 mmHg) versus TT genotype (77.3±7.3 mmHg; P=0.011). Added salt intake was significantly higher in AA genotype compared to TT genotype (P=0.010). For rs224534 (TRPV1), sodium intake was significantly lower in TT genotype (3767.0±713.7 mg/day) compared to CC genotype (4633.3±793.5 mg/day; P=0.012). No significant associations were found between any SNPs and systolic BP, nor between rs224534, rs4790151, or rs8065080 and diastolic BP. No significant associations were found for rs4790151 or rs8065080 with sodium intake or BP.

**Clinical Implications:** This study provides evidence that genetic variations in salt taste receptor genes (SCNN1B rs239345 and TRPV1 rs224534) are associated with sodium intake and diastolic BP in an Iranian population. These findings suggest that genetic factors influencing salt taste perception may contribute to hypertension risk and ultimately CVD risk. Understanding genetic variation in taste perception could lead to personalized dietary approaches for reducing CVD risk. However, the study has limitations including small sample size (n=116), limited SNP coverage, single 24-hour urine collection, and lack of adjustment for age, sex, and BMI. Further studies with larger sample sizes are warranted to replicate these findings and examine potential gene-gene interactions.