RENAL SODIUM HANDLING IN RELATION TO ENVIRONMENTAL AND GENETIC FACTORS IN UNTREATED CHINESE

Abstract

Objective: Renal tubular sodium handling plays a key role in blood pressure regulation. Several studies reported association between higher proximal tubule fractional reabsorption of sodium and genetic variations response to blood pressure, but no previous study evaluated the contributions of environmental and genetic cues to renal sodium handling in a population-based study. Design and method: Our study subjects were suspected hypertensive patients being off antihypertensive medication for at least 2 weeks and referred to our hypertension clinic for 24-hour ambulatory blood pressure monitoring. We collected serum and 24-hour urine for measurement of sodium, creatinine and lithium concentration. Sodium and creatinine concentrations were measured by coupled plasma mass spectrometry. Fractional excretion of lithium (FELi) and fractional distal reabsorption rate of sodium (FDRNa) were calculated as markers of proximal and distal sodium handling, respectively. We used the ABI SNapShot method and genotyped 12 SNPs from candidate genes (ADD1, ADD2, ADD3, LSS, ABCB1, HSD3B1, NEDD4L, AGTR1 and WNK1) and 6 SNPs (rs10502933, rs2345088, rs12513375, rs16817782, rs2461911, rs16893522) generated from a genome wide association study. Results: The 1409 study participants included 664 men and had a mean age of 51.0 years. In adjusted analysis, FELi was positively associated with age but negatively with the total-to-high density lipoprotein cholesterol ratio. FDRNa was negatively associated with current smoking and waist circumference (P < = 0.003). Both indexes were also significantly associated with season and humidity explaining with ∼1.3% and ∼3.5% of the variance, respectively. After adjustment for host and environmental factors and Bonferroni multiple testing, among the 19 studied genetic variants, only rs12513375 potentially play a role in sodium reabsorption and was significantly associated with either FELi or FDRNa of the variance and explained about 1.7% of the variance. Conclusions: In conclusion, renal sodium handling as measured by endogenous lithium clearance was sensitive to major host, environmental and genetic factors.