MyMedR

Displaying all 8 publications

Abstract:

Sort:

Recent Advances in the Genetics of Hypertension

Wei LK, Au A, Teh LK, Lye HS

Adv Exp Med Biol, 2017;956:561-581.
PMID: 27957710 DOI: 10.1007/5584_2016_75

Hypertension is a silent killer worldwide, caused by both genetic and environmental factors. Until now, genetic and genomic association studies of hypertension are reporting different degree of association on hypertension. Hence, it is essential to gather all the available information on the reported genetic loci and to determine if any biomarker(s) is/are significantly associated with hypertension. Current review concluded the potential biomarkers for hypertension, with regards to electrolyte and fluid transports, as well as sodium/potassium ions homeostasis, which are supported by the results of case-controls and meta-analyses.

Matched MeSH terms: Blood Pressure/genetics*
Signaling pathway genes for blood pressure, folate and cholesterol levels among hypertensives: an epistasis analysis

Wei LK, Menon S, Griffiths LR, Gan SH

J Hum Hypertens, 2015 Feb;29(2):99-104.
PMID: 25055800 DOI: 10.1038/jhh.2014.53

Irregular atrial pressure, defective folate and cholesterol metabolism contribute to the pathogenesis of hypertension. However, little is known about the combined roles of the methylenetetrahydrofolate reductase (MTHFR), apolipoprotein-E (ApoE) and angiotensin-converting enzyme (ACE) genes, which are involved in metabolism and homeostasis. The objective of this study is to investigate the association of the MTHFR 677 C>T and 1298A>C, ACE insertion-deletion (I/D) and ApoE genetic polymorphisms with hypertension and to further explore the epistasis interactions that are involved in these mechanisms. A total of 594 subjects, including 348 normotensive and 246 hypertensive ischemic stroke subjects were recruited. The MTHFR 677 C>T and 1298A>C, ACE I/D and ApoEpolymorphisms were genotyped and the epistasis interaction were analyzed. The MTHFR 677 C>T and ApoE polymorphisms demonstrated significant associations with susceptibility to hypertension in multiple logistic regression models, multifactor dimensionality reduction and a classification and regression tree. In addition, the logistic regression model demonstrated that significant interactions between the ApoE E3E3, E2E4, E2E2 and MTHFR 677 C>T polymorphisms existed. In conclusion, the results of this epistasis study indicated significant association between the ApoE and MTHFR polymorphisms and hypertension.

Matched MeSH terms: Blood Pressure/genetics
Fulltext Association of beta 2 adrenoceptor gene polymorphisms in Malaysian hypertensive subjects

Komara M, Vasudevan R, Ismail P, Bakar SA, Pishva SR, Heidari F

Genet. Mol. Res., 2014;13(2):2939-48.
PMID: 24782128 DOI: 10.4238/2014.April.16.2

The sympathetic nervous system plays a major role in blood pressure regulation. Beta 2 (β2) adrenoceptor gene polymorphisms have been associated with hypertension in different populations with conflicting results. We examined the association of three common polymorphisms, Arg16Gly, Gln27Glu, and Thr164Ile, of the β2 adrenoceptor gene in Malaysian hypertensive subjects. A total of 160 hypertensive and control subjects were recruited. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and anthropometric measurements were obtained from each subject. Biochemical analyses of lipid profiles were conducted with an autoanalyzer. DNA samples were extracted from blood and buccal cells. Genotyping was accomplished with polymerase chain reaction-restriction fragment length polymorphism. SBP, DBP, body mass index, and biochemical factors all differed significantly between case and control subjects (P < 0.05). The genotype frequencies of Arg16Arg, Arg16Gly, and Gly16Gly were 22.5, 70, and 7.5% among cases and 33.1, 63.1, and 3.8% among controls, respectively. The genotype frequencies of Gln27Gln, Gln27Glu, and Glu27Glu among cases were 41.1, 50, and 1.9% compared to 77.5, 20.6, and 1.9% among controls, respectively. In this study, the Gln27Glu polymorphism was significantly associated with Malaysian hypertensive subjects (P < 0.05). Therefore, the Gln27Glu polymorphism of the β2 adrenoceptor could be a risk factor associated with hypertension among Malaysians.

Matched MeSH terms: Blood Pressure/genetics*
Association of melanocortin-4 receptor gene polymorphisms with obesity-related parameters in Malaysian Malays

Apalasamy YD, Ming MF, Rampal S, Bulgiba A, Mohamed Z

Ann Hum Biol, 2013 Jan;40(1):102-6.
PMID: 22989167 DOI: 10.3109/03014460.2012.720709

Melanocortin-4 receptor (MC4R) is an important regulator of body weight and energy intake. Genetic polymorphisms of the MC4R gene have been found to be linked to obesity in many recent studies across the globe.

Matched MeSH terms: Blood Pressure/genetics
Fulltext The Association of Estrogen Receptor-β Gene Variation With Salt-Sensitive Blood Pressure

Manosroi W, Tan JW, Rariy CM, Sun B, Goodarzi MO, Saxena AR, et al.

J Clin Endocrinol Metab, 2017 11 01;102(11):4124-4135.
PMID: 28938457 DOI: 10.1210/jc.2017-00957

Context: Hypertension in young women is uncommon compared with young men and older women. Estrogen appears to protect most women against hypertension, with incidence increasing after menopause. Because some premenopausal women develop hypertension, estrogen may play a different role in these women. Genetic variations in the estrogen receptor (ER) are associated with cardiovascular disease. ER-β, encoded by ESR2, is the ER predominantly expressed in vascular smooth muscle.
Objective: To determine an association of single nucleotide polymorphisms in ESR2 with salt sensitivity of blood pressure (SSBP) and estrogen status in women.
Methods: Candidate gene association study with ESR2 and SSBP conducted in normotensive and hypertensive women and men in two cohorts: International Hypertensive Pathotype (HyperPATH) (n = 584) (discovery) and Mexican American Hypertension-Insulin Resistance Study (n = 662) (validation). Single nucleotide polymorphisms in ESR1 (ER-α) were also analyzed. Analysis conducted in younger (<51 years, premenopausal, "estrogen-replete") and older women (≥51 years, postmenopausal, "estrogen-deplete"). Men were analyzed to control for aging.
Results: Multivariate analyses of HyperPATH data between variants of ESR2 and SSBP documented that ESR2 rs10144225 minor (risk) allele carriers had a significantly positive association with SSBP driven by estrogen-replete women (β = +4.4 mm Hg per risk allele, P = 0.004). Findings were confirmed in Hypertension Insulin-Resistance Study premenopausal women. HyperPATH cohort analyses revealed risk allele carriers vs noncarriers had increased aldosterone/renin ratios. No associations were detected with ESR1.
Conclusions: The variation at rs10144225 in ESR2 was associated with SSBP in premenopausal women (estrogen-replete) and not in men or postmenopausal women (estrogen-deplete). Inappropriate aldosterone levels on a liberal salt diet may mediate the SSBP.

Matched MeSH terms: Blood Pressure/genetics
Fulltext Genetic Predictors of Salt Sensitivity of Blood Pressure: The Additive Impact of 2 Hits in the Same Biological Pathway

Haas AV, En Yee L, Yuan YE, Wong YH, Hopkins PN, Jeunemaitre X, et al.

Hypertension, 2021 Dec;78(6):1809-1817.
PMID: 34757767 DOI: 10.1161/HYPERTENSIONAHA.121.18033

[Figure: see text].

Matched MeSH terms: Blood Pressure/genetics*
Uncoupling protein 2 promoter polymorphism -866G/A, central adiposity, and metabolic syndrome in Asians

Shen H, Qi L, Tai ES, Chew SK, Tan CE, Ordovas JM

Obesity (Silver Spring), 2006 Apr;14(4):656-61.
PMID: 16741267

A polymorphism in the promoter region of uncoupling protein 2 gene -866G/A has been associated with its expression levels in adipose tissue, the risk of obesity, and metabolic abnormalities. Our purpose was to examine the associations of -866G/A with body fat and the risk of metabolic syndrome in a random sample of 4018 Asians (1858 men and 2160 women) from three ethnic groups (Chinese, Malay, and Indian). The minor allele frequency of -866G/A polymorphism in South Asians was similar to that in whites. After adjustment for covariates including age, cigarette smoking, and physical activity, the -866A/A genotype was associated with higher waist-to-hip ratio as compared with the wild-type genotype in Chinese and Indian men (p = 0.018 and p = 0.046, respectively). Moreover, Indian men with -866A/A genotype had a significantly increased risk of metabolic syndrome as compared with those homozygous for the wild-type (odds ratio, 2.66; 95% confidence interval, 1.21 to 5.88; p = 0.015). Such a risk was mainly caused by the excess presence of hypertriglyceridemia and central obesity. Our findings indicate that the uncoupling protein 2 gene -866G/A polymorphism may increase the risks of central obesity and metabolic syndrome, with greater effects on Asian men.

Matched MeSH terms: Blood Pressure/genetics
Fulltext Lysine-Specific Demethylase-1 Deficiency Increases Agonist Signaling Via the Mineralocorticoid Receptor

Treesaranuwattana T, Wong KYH, Brooks DL, Tay CS, Williams GH, Williams JS, et al.

Hypertension, 2020 04;75(4):1045-1053.
PMID: 32160100 DOI: 10.1161/HYPERTENSIONAHA.119.13821

LSD1 (lysine-specific demethylase-1) is an epigenetic regulator of gene transcription. LSD1 risk allele in humans and LSD1 deficiency (LSD1+/-) in mice confer increasing salt-sensitivity of blood pressure with age, which evolves into salt-sensitive hypertension in older individuals. However, the mechanism underlying the relationship between LSD1 and salt-sensitivity of blood pressure remains elusive. Here, we show that LSD1 genotype (in humans) and LSD1 deficiency (in mice) lead to similar associations with increased blood pressure and urine potassium levels but with decreased aldosterone levels during a liberal salt diet. Thus, we hypothesized that LSD1 deficiency leads to an MR (mineralocorticoid receptor)-dependent hypertensive state. Yet, further studies in LSD1+/- mice treated with the MR antagonist eplerenone demonstrate that hypertension, kaliuria, and albuminuria are substantially improved, suggesting that the ligand-independent activation of the MR is the underlying cause of this LSD1 deficiency-mediated phenotype. Indeed, while MR and epithelial sodium channel expression levels were increased in LSD1+/- mouse kidney tissues, aldosterone secretion from LSD1+/- glomerulosa cells was significantly lower. Collectively, these data establish that LSD1 deficiency leads to an inappropriate activation and increased levels of the MR during a liberal salt regimen and suggest that inhibiting the MR pathway is a useful strategy for treatment of hypertension in human LSD1 risk allele carriers.

Matched MeSH terms: Blood Pressure/genetics*