scholarly journals Genetic Predictors of Salt Sensitivity of Blood Pressure: The Additive Impact of 2 Hits in the Same Biological Pathway

Hypertension ◽  
2021 ◽  
Vol 78 (6) ◽  
pp. 1809-1817
Author(s):  
Andrea V. Haas ◽  
Li En Yee ◽  
Yan E. Yuan ◽  
Yin H. Wong ◽  
Paul N. Hopkins ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Risk Allele ◽  
Salt Sensitivity ◽  
Nucleotide Polymorphisms ◽  
Aldosterone Secretion ◽  
Mineralocorticoid Receptor Antagonist ◽  
Single Nucleotide ◽  
Genetic Predictors ◽  
Serum Aldosterone ◽  
Cardiovascular Morbidity And Mortality

Salt sensitivity of blood pressure is associated with increased cardiovascular morbidity and mortality. A diplotype in the β2AR gene (rs1042713, rs1042714) and single nucleotide polymorphisms in ESR2 (rs10144225), SGK1 (rs2758151), and AGT (rs2493134) genes are all independently associated with salt sensitivity of blood pressure and all but AGT are associated with increased aldosterone levels and/or activity. We sought to determine whether individuals who carried a double hit risk phenotype—a risk allele associated with increased aldosterone secretion (either β2AR or ESR2 ) and a risk allele associated with amplification of aldosterone’s effects ( SGK1 ) would result in more significant SSBP compared with individuals homozygous for a single risk allele. Data were obtained from the Hypertension Pathotypes cohort where individuals completed 7 days of restricted sodium and liberal sodium diets. We defined 3 genetic combinations: β2AR/SGK, ESR2/SGK , and AGT/SGK. Multivariate regression analyses found a significantly higher salt sensitivity of blood pressure as the number of risk allele pairs increased in both the β2AR/SGK (β=5.46; P <0.001) and ESR2/SGK ( β =4.87; P 0.01). In addition, the number of risk allele pairs was associated with serum aldosterone levels for β2AR/SGK and ESR2/SGK . On the other hand, there was no association between the number of risk allele pairs with salt sensitivity of blood pressure nor aldosterone levels in the AGT/SGK combination. In conclusion, genetic combinations of β2AR/SGK1 and ESR2 / SGK1 are associated with greater salt sensitivity of blood pressure and plasma aldosterone concentrations. Hypertensive combination risk homozygotes may be candidates for mineralocorticoid receptor antagonist therapy—gene-driven, personalized medicine.

scholarly journals Evidence GDF15 Plays a Role in Familial and Recurrent Hyperemesis Gravidarum

2018 ◽  
Vol 78 (09) ◽  
pp. 866-870 ◽  
Author(s):  
Marlena Fejzo ◽  
Daria Arzy ◽  
Rayna Tian ◽  
Kimber MacGibbon ◽  
Patrick Mullin
Keyword(s):  
Genome Wide Association Study ◽  
Risk Allele ◽  
Hyperemesis Gravidarum ◽  
Nucleotide Polymorphisms ◽  
Sequencing Data ◽  
Severe Nausea ◽  
Single Nucleotide ◽  
Genome Wide ◽  
History Of ◽  
Study Support

Abstract Introduction Hyperemesis gravidarum (HG), a pregnancy complication characterized by severe nausea and vomiting in pregnancy, occurs in up to 2% of pregnancies. It is associated with both maternal and fetal morbidity. HG is highly heritable and recurs in approximately 80% of women. In a recent genome-wide association study, it was shown that placentation, appetite, and the cachexia gene GDF15 are linked to HG. The purpose of this study was to explore whether GDF15 alleles linked to overexpression of GDF15 protein segregate with the condition in families, and whether the GDF15 risk allele is associated with recurrence of HG. Methods We analyzed GDF15 overexpression alleles for segregation with disease using exome-sequencing data from 5 HG families. We compared the allele frequency of the GDF15 risk allele, rs16982345, in patients who had recurrence of HG with its frequency in those who did not have recurrence. Results Single nucleotide polymorphisms (SNPs) linked to higher levels of GDF15 segregated with disease in HG families. The GDF15 risk allele, rs16982345, was associated with an 8-fold higher risk of recurrence of HG. Conclusion The findings of this study support the hypothesis that GDF15 is involved in the pathogenesis of both familial and recurrent cases of HG. The findings may be applicable when counseling women with a familial history of HG or recurrent HG. The GDF15-GFRAL brainstem-activated pathway was recently identified and therapies to treat conditions of abnormal appetite are under development. Based on our findings, patients carrying GDF15 variants associated with GDF15 overexpression should be included in future studies of GDF15-GFRAL-based therapeutics. If safe, this approach could reduce maternal and fetal morbidity.

scholarly journals Black Carbon Exposures, Blood Pressure, and Interactions with Single Nucleotide Polymorphisms in MicroRNA Processing Genes

2010 ◽  
Vol 118 (7) ◽  
pp. 943-948 ◽  
Author(s):  
Elissa H. Wilker ◽  
Andrea Baccarelli ◽  
Helen Suh ◽  
Pantel Vokonas ◽  
Robert O. Wright ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Single Nucleotide Polymorphisms ◽  
Black Carbon ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Microrna Processing

scholarly journals Salt-Sensitivity of Blood Pressure and Insulin Resistance

2021 ◽  
Vol 12 ◽  
Author(s):  
Lale A. Ertuglu ◽  
Fernando Elijovich ◽  
Cheryl L. Laffer ◽  
Annet Kirabo
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Insulin Sensitivity ◽  
Immune Activation ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Salt Sensitivity ◽  
Common Denominator ◽  
Peroxisome Proliferator ◽  
Cardiovascular Morbidity And Mortality

Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular morbidity and mortality that is seen in both hypertensive and normotensive populations. Insulin resistance (IR) strongly correlates with SSBP and affects nearly 50% of salt sensitive people. While the precise mechanism by which IR and SSBP relate remains elusive, several common pathways are involved in the genesis of both processes, including vascular dysfunction and immune activation. Vascular dysfunction associated with insulin resistance is characterized by loss of nitric oxide (NO)-mediated vasodilation and heightened endothelin-1 induced vasoconstriction, as well as capillary rarefaction. It manifests with increased blood pressure (BP) in salt sensitive murine models. Another common denominator in the pathogenesis of insulin resistance, hypertension, and salt sensitivity (SS) is immune activation involving pro-inflammatory cytokines like tumor necrosis factor (TNF)-α, IL-1β, and IL-6. In the last decade, a new understanding of interstitial sodium storage in tissues such as skin and muscle has revolutionized traditional concepts of body sodium handling and pathogenesis of SS. We have shown that interstitial Na+ can trigger a T cell mediated inflammatory response through formation of isolevuglandin protein adducts in antigen presenting cells (APCs), and that this response is implicated in salt sensitive hypertension. The peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that modulates both insulin sensitivity and BP. PPARγ agonists increase insulin sensitivity and ameliorate salt sensitivity, whereas deficiency of PPARγ results in severe insulin resistance and hypertension. These findings suggest that PPARγ plays a role in the common pathogenesis of insulin sensitivity and salt sensitivity, perhaps via effects on the immune system and vascular function. The goal of this review is to discuss those mechanisms that may play a role in both SSBP and in insulin resistance.

scholarly journals The Effect of Antihypertensive Medications on Testing for Primary Aldosteronism

2021 ◽  
Vol 12 ◽  
Author(s):  
Piotr Jędrusik ◽  
Bartosz Symonides ◽  
Jacek Lewandowski ◽  
Zbigniew Gaciong
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Drug ◽  
Primary Aldosteronism ◽  
Angiotensin Receptor Blockers ◽  
Suboptimal Control ◽  
Aldosterone Secretion ◽  
Antihypertensive Medications ◽  
Specific Patient ◽  
Drug Classes ◽  
Cardiovascular Morbidity And Mortality

Primary aldosteronism (PA) is a potentially curable form of secondary hypertension caused by excessive renin-independent aldosterone secretion, leading to increased target organ damage and cardiovascular morbidity and mortality. The diagnosis of PA requires measuring renin and aldosterone to calculate the aldosterone-to-renin ratio, followed by confirmatory tests to demonstrate renin-independent aldosterone secretion and/or PA subtype differentiation. Various antihypertensive drug classes interfere with the renin-angiotensin-aldosterone axis and hence evaluation for PA should ideally be performed off-drugs. This is, however, often precluded by the risks related to suboptimal control of blood pressure and serum potassium level in the evaluation period. In the present review, we summarized the evidence regarding the effect of various antihypertensive drug classes on biochemical testing for PA, and critically appraised the issue whether and which antihypertensive medications should be withdrawn or, conversely, might be continued in patients evaluated for PA. The least interfering drugs are calcium antagonists, alpha-blockers, hydralazine, and possibly moxonidine. If necessary, the testing may also be attempted during treatment with beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers but renin and aldosterone measurements must be interpreted in the context of known effects of these drugs on these parameters. Views are evolving on the feasibility of testing during treatment with mineralocorticoid receptor antagonists, as these drugs are now increasingly considered acceptable in specific patient subsets, particularly in those with severe hypokalemia and/or poor blood pressure control on alternative treatment.

scholarly journals FASN, SCD1 and ANXA9 gene polymorphism as genetic predictors of the fatty acid profile of sheep milk

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ewa Pecka-Kiełb ◽  
Inga Kowalewska-Łuczak ◽  
Ewa Czerniawska-Piątkowska ◽  
Bożena Króliczewska
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Saturated Fatty Acids ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Fatty Acids Profile ◽  
Sheep Milk ◽  
Genetic Predictors ◽  
Pcr Rflp

AbstractIn this study, single nucleotide polymorphisms (SNPs) in the ANXA9 (annexin 9), FASN (fatty acid synthase) and SCD1 (stearoyl-CoA desaturase 1) genes were analyzed as factors influencing fatty acid profiles in milk from Zošľachtená valaška sheep. SNP in selected genes was identified using polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR–RFLP). The long-chain fatty acids profile in sheep milk was identified by gas chromatography. Statistical analysis of the SCD1/Cfr13I polymorphism showed that the milk of the homozygous AA animals was characterized by a lower (P < 0.05) share of C4:0, C6:0, C8:0, C10:0, C12:0, C14:0 in comparison to the homozygous CC sheep. The milk of heterozygous sheep was characterized by a higher (P < 0.05) proportion of C13:0 acid compared to the milk of sheep with the homozygous AA type. A higher (P < 0.05) level of saturated fatty acids (SFA) was found in the milk of CC genotype sheep compared to the AA genotype. Our results lead to the conclusion that the greatest changes were observed for the SCD1/Cfr13I polymorphism and the least significant ones for FASN/AciI. Moreover, it is the first evidence that milk from sheep with SCD1/Cfr13I polymorphism and the homozygous AA genotype showed the most desirable fatty acids profile.

scholarly journals Effects of environmental and genetic risk factors for salt sensitivity on blood pressure in northern China: the systemic epidemiology of salt sensitivity (EpiSS) cohort study

BMJ Open ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. e023042 ◽  
Author(s):  
Han Qi ◽  
Bin Liu ◽  
Chunyue Guo ◽  
Zheng Liu ◽  
Han Cao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Northern China ◽  
Salt Sensitivity ◽  
Urine Samples ◽  
Liaoning Province ◽  
Nucleotide Polymorphisms ◽  
Spot Urine ◽  
Face To Face ◽  
Non Coding Rnas

PurposeThe systemic epidemiology of salt sensitivity (EpiSS) study aims to combine molecular biology, epidemiology and bioinformatics methods to discover the potential causes of salt sensitivity of blood pressure (SSBP) using single-nucleotide polymorphisms in the genome and non-coding RNAs in the transcriptome to uncover both the genetic and environmental factors of SSBP.ParticipantsBetween July 2014 and July 2016, we enrolled adults from 11 study centres in Beijing and Liaoning Province; participants were of the Han population and were 35–70 years of age. We collected blood samples, spot urine samples and 24-hour urine samples, in addition to baseline data on demographics, health-related lifestyle factors, chronic diseases, family history of illness and anthropometric information through face-to-face interviews using a standardised questionnaire. EpiSS uses the modified Sullivan’s acute oral saline load and diuresis shrinkage test (MSAOSL-DST) to evaluate the effects of salt on blood pressure.Findings to dateIn total, 2163 participants were included in the EpiSS, of which 2144 participants completed the questionnaire, 2120 (98.0%) completed the MSAOSL-DST and 2083 (96.3%) provided a 24-hour urine sample. A total of 2057 participants (1501 women and 556 men) completed all the steps of the investigation and were included in the analysis. Among them, 583 (28.3%) subjects were classified as having salt sensitivity of blood pressure, and 1061 (51.6%) had hypertension.Future plansThe next step of our study is to evaluate the incidence of cardiovascular disease in the participants. Biennial follow-up, including face-to-face questionnaire surveys, laboratory measurements of blood, urinary creatinine, glomerular filtration rate and anthropometric measurements, will occur two additional times. DNA and RNA will be collected for subsequent genetic biomarker studies. We plan on screening the salt-sensitive-related gene loci and non-coding RNAs based on relative environmental risk factors.Trial registration numberChiCTR-EOC-16009980; Pre-results.

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