Study of rs10177833 polymorphism in SLC4A5 gene and salt sensitivity in Bulgarian population

Abstract

High sodium intake is associated with increased blood pressure and and increased risk of cardiovascular disease (CVD). Among the countries of the European Union, Bulgaria ranks first in mortality from CVD. Genetically determined salt sensitivity is present in 50% of the hypertensive and 26% of the normotensive population, posing a major public health problem. The present study was conducted within the National Program for Prevention of Chronic Non-Communicable Diseases 2014 - 2020 to assess the sodium intake of the population in Bulgaria. 36 normotensive participants are included in the study. DNA from each volunteers was isolated and genotyped for rs10177833 (A>C) in SLC4A5 gene by TaqMan SNP genotyping assay. To determine the 24-hour urinary excretion of sodium in the subjects, a random sample was taken from each participant. Sodium concentration was determined by atomic absorption spectrometry. A WHO protocol has been used to recalculate sodium excretion (Protocol for Sodium Determination in 24-hour Urine Samples). Eighteen of total of 35 participants had wild AA genotype (51.43%), thirteen were heterozygotes (37.14%) and four were carriers of two polymorphic C alleles (11.43%). The frequency of A allele of rs10177833 (A>C) in SLC4A5 gene was 70%, whereas polymorphic C allele was only 30%. The correlation analysis showed negative statistical significant relationship between rs10177833 in SLC4A5 gene and sodium concentration (in milligrams) in 24 - hours urine (r = -0.365, p = 0.031). Also the holders of CC genotype had significant lower values of Na compared to these with wild AA genotype (p = 0.01) and compared to heterozygotes (p = 0.019). In conclusion, we found a clear relationship between the polymorphic variant rs10177833 in SLC4A5 gene and the concentration of sodium in urine in Bulgarian normotensives. The tendency of association was found between the studied polymorphic variant and blood pressure values, which should be studied in a large number of participants Key messages Increasing the population's awareness of health risks with increased salt consumption. Regular monitoring of salt consumption.

Hypertensive heart disease: risk factors, complications and mechanisms

“…While significantly elevating blood pressure in some individuals (salt sensitivity), excess salt has no effect on blood pressure in others (salt resistant) and there is a group of individuals (about 15%) whose blood pressure increases with low salt intake (inverse salt sensitivity) (127)(128)(129). Salt sensitivity of blood pressure (SSBP) results in part from genetic polymorphisms in genes regulating sodium handling and those not related to sodium handling such as the Protein Kinase CGMP-Dependent 1 (PRKG1), cytochrome b-245 alpha (CYBA) chain (also known as p22-phox), branched chain amino acid transaminase 1 (BCAT1), Solute Carrier Family 8 Member A1 (SLC8A1), SLC4A5, Angiotensin II Receptor Type 1 (AGTR1), Selectin E (SELE), cytochrome P450 family 4 subfamily A member 11 (CYP4A11), Neuronal precursor cell expressed developmentally down-regulated 4-like (NEDD4l) and Visinin Like 1 (VSNL1) (129)(130)(131)(132)(133). As explained above, RAAS activation leads to vasoconstriction, increased systemic vascular resistance (SVR) and elevation in blood pressure (134).…”