J Nutr Health.  2017 Jun;50(3):217-224. 10.4163/jnh.2017.50.3.217.

Salt-sensitive genes and their relation to obesity

• Cheon YP
• Lee M

• KMID: 2386623
• DOI: http://doi.org/10.4163/jnh.2017.50.3.217

Abstract

PURPOSE
Although it is well known thatmortality and morbidity due to cardiovascular diseases are higher in salt-sensitive subjects than in salt-resistant subjects, their underlying mechanisms related to obesity remain unclear. Here, we focused on salt-sensitive gene variants unrelated to monogenic obesity that interacted with sodium intake in humans.
METHODS
This review was written based on the modified 3(rd) step of Khans' systematic review. Instead of the literature, subject genes were based on candidate genes screened from our preliminary Genome-Wide Association Study (GWAS). Finally, literature related to five genes strongly associated with salt sensitivity were analyzed to elucidate the mechanism of obesity.
RESULTS
Salt sensitivity is a measure of how blood pressure responds to salt intake, and people are either salt-sensitive or salt-resistant. Otherwise, dietary sodium restriction may not be beneficial for everyone since salt sensitivity may be associated with inherited susceptibility. According to our previous GWAS studies, 10 candidate genes and 11 single nucleotide polymorphisms (SNPs) associated with salt sensitivity were suggested, including angiotensin converting enzyme (ACE), α-adducin1 (ADD1), angiotensinogen (AGT), cytochrome P450 family 11-subfamily β-2 (CYP11β-2), epithelial sodium channel (ENaC), G-protein b3 subunit (GNB3), G protein-coupled receptor kinases type 4 (GRK4 A142V, GRK4 A486V), 11β-hydroxysteroid dehydrogenase type-2 (HSD 11β-2), neural precursor cell-expressed developmentally down regulated 4 like (NEDD4L), and solute carrier family 12(sodium/chloride transporters)-member 3 (SLC 12A3). We found that polymorphisms of salt-sensitive genes such as ACE, CYP11β-2, GRK4, SLC12A3, and GNB3 may be positively associated with human obesity.
CONCLUSION
Despite gender, ethnic, and age differences in genetics studies, hypertensive obese children and adults who are carriers of specific salt-sensitive genes are recommended to reduce their sodium intake. We believe that our findings can contribute to the prevention of early-onset of chronic diseases in obese children by facilitating personalized diet-management of obesity from childhood to adulthood.

Keyword

sodium-sensitive genes; GWAS; obesity; hypertension

MeSH Terms

Adult
Angiotensinogen
Blood Pressure
Cardiovascular Diseases
Child
Chronic Disease
Cytochrome P-450 Enzyme System
Epithelial Sodium Channels
Genetics
Genome-Wide Association Study
GTP-Binding Proteins
Humans
Hypertension
Obesity*
Oxidoreductases
Peptidyl-Dipeptidase A
Phosphotransferases
Polymorphism, Single Nucleotide
Sodium
Sodium, Dietary
Angiotensinogen
Cytochrome P-450 Enzyme System
Epithelial Sodium Channels
GTP-Binding Proteins
Oxidoreductases
Peptidyl-Dipeptidase A
Phosphotransferases
Sodium
Sodium, Dietary

Reference

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