Identifying Interactions between Dietary Sodium, Potassium, Sodium–Potassium Ratios, and FGF5 rs16998073 Variants and Their Associated Risk for Hypertension in Korean Adults

Abstract

Hypertension is affected by both genetic and dietary factors. This study aimed to examine the interaction between dietary sodium/potassium intake, sodium–potassium ratios, and FGF5 rs16998073 and link these with increased risk for developing hypertension. Using data from the Health Examinee (HEXA) Study of the Korean Genome and Epidemiologic Study (KoGES), we were able to identify a total of 17,736 middle-aged Korean adults who could be included in our genome-wide association study (GWAS) to confirm any associations between hypertension and the FGF5 rs16998073 variant. GWAS analysis revealed that the FGF5 rs16698073 variant demonstrated the strongest association with hypertension in this population. Multivariable logistic regression was used to examine the relationship between dietary intake of sodium, potassium, and sodium–potassium ratios and the FGF5 rs16998073 genotypes (AA, AT, TT) and any increased risk of hypertension. Carriers with at least one minor T allele for FGF5 rs16998073 were shown to be at significantly higher risk for developing hypertension. Male TT carriers with a daily sodium intake ≥2000 mg also demonstrated an increased risk for developing hypertension compared to the male AA carriers with daily sodium intake <2000 mg (adjusted odds ratio (AOR) = 2.41, 95% confidence intervals (CIs) = 1.84–3.15, p-interaction < 0.0001). Female AA carriers with a daily potassium intake ≥3500 mg showed a reduced risk for hypertension when compared to female AA carriers with a daily potassium intake <3500 mg (AOR = 0.75. 95% CIs = 0.58–0.95, p-interaction < 0.0001). Male TT carriers in the mid-tertile for sodium–potassium ratio values showed the highest odds ratio for hypertension when compared to male AA carriers in the lowest-tertile for sodium–potassium ratio values (AOR = 3.03, 95% CIs = 2.14–4.29, p-interaction < 0.0001). This study confirmed that FGF5 rs16998073 variants do place their carriers (men and women) at increased risk for developing hypertension. In addition, we showed that high daily intake of sodium exerted a synergistic effect for hypertension when combined with FGF5 rs16998073 variants in both genders and that dietary sodium, potassium, and sodium–potassium ratios all interact with FGF5 rs16998073 and alter the risk of developing hypertension in carriers of either gender among Koreans.

A Genome-Wide Association Study of a Korean Population Identifies Genetic Susceptibility to Hypertension Based on Sex-Specific Differences

“…The significance was independently reproducible in the genetic association analysis of hypertension with a Chinese population [31]. The other two variants also showed a significant result in previous GWASs [32,33]. In the total population EWASs for SBP and DBP, there were no exome-wide significant results with the adjusted p value.…”

“…Moreover, the rs2074356 of HECTD4 had significant sex-specific genetic effects. Furthermore, the locus was associated with hypertension in a previous GWAS [33]. HECTD4 is an E3 ubiquitin ligase that is associated with androgen receptor promotion in prostate cancer cell lines [54].…”

High Concentration of Heavy Metal and Metalloid Levels in Edible Campomanesia adamantium Pulp from Anthropic Areas

“…However, K concentrations in this pulp are near blueberry and alfalfa (39 mg/100 g) [ 38 ]. The health benefit of K in the body is associated with blood pressure regulation, stroke risk reduction, preventing renal system dysfunction, decreasing urinary calcium excretion, reducing kidney stone formation and osteoporosis disease [ 40 ], regulating blood lipid concentrations [ 36 ] and maintaining bone and cardiovascular health [ 41 , 42 , 43 ].…”

Genome-wide association study of ischemic stroke risk in Sickle Cell confirms ADAMTS2, CDK18, uncovers 12 novel loci

“…genes from the current study, CUX1, CNNM2, and NUDT4, have been previously associated with higher reticulocyte counts 34 35 . CNNM2 has also been linked to numerous stroke related traits -hypertension, coronary artery disease, and mean corpuscular hemoglobin [36][37][38][39][40][41][42][43] . CNNM2 gene is expressed throughout the body but is particularly high in the brain, kidney, and endocrine tissue 44 and appears to play a role in renal magnesium uptake 45,46 Pathway analysis also uncovered enrichment of variants in genes involved with the platelet dense tubular network.…”