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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: Hypertension/genetics*
Reduction in arterial stiffness with angiotensin II antagonism and converting enzyme inhibition. A comparative study among malay hypertensive subjects with a known genetic profile

Rehman A, Ismail SB, Naing L, Roshan TM, Abdul Rahman AR

Am J Hypertens, 2007 Feb;20(2):184-9.
PMID: 17261465 DOI: 10.1016/j.amjhyper.2006.07.015

BACKGROUND: Data comparing the effect of losartan and perindopril on aortic stiffness among hypertensive subjects without A(1166)C polymorphism was not available.
METHODS: The short-term and long-term effects of losartan (50 mg) and perindopril (4 mg) on aortic stiffness measured as carotid femoral pulse wave velocity (PWV) were compared in 39 middle-aged Malay subjects with mild-to-moderate hypertension in a 4-month, double-blind, randomized, controlled, parallel-design study.
RESULTS: Four-month treatment with both drugs showed a significant reduction in blood pressure (BP) (P < .005) and PWV (P < .05) as compared to the baseline. On the other hand 1-month treatment showed a significant reduction in BP only in perindopril group (P < .05) but not in the losartan group. There was no significant reduction in pulse pressure and PWV after 1 month treatment by both drugs. No significant difference was seen in reduction in BP after 1 month and 4 months treatment between the two drugs. Similarly no significant difference was seen in reduction in PWV between the two drugs after 1 month (P = .613) and 4 months (P = .521) of treatment. Reduction in PWV by losartan (r = 0.470) and perindopril (r = 0.457) correlated significantly only with reduction in DBP (P < .05) and remained significant even after controlling for reduction in DBP (P < .05). Reduction in PWV by both losartan and perindopril was independent of reduction in BP by these drugs.
CONCLUSIONS: These results showed that long-term treatment with losartan shows similar pressure independent reduction in PWV as perindopril among Malay hypertensive subjects with a homogenous "AA" genotype for angiotensin II type 1 receptor and may serve as a suitable alternative to perindopril.

Matched MeSH terms: Hypertension/genetics
alpha-Tocopherol increased nitric oxide synthase activity in blood vessels of spontaneously hypertensive rats

Newaz MA, Nawal NN, Rohaizan CH, Muslim N, Gapor A

Am J Hypertens, 1999 Aug;12(8 Pt 1):839-44.
PMID: 10480480

Antioxidant protection provided by different doses of alpha-tocopherol was compared by determining nitric oxide synthase (NOS) activity in blood vessels of spontaneously hypertensive rats (SHR) treated with alpha-tocopherol. SHR were divided into four groups namely hypertensive control (C), treatment with 17 mg of alpha-tocopherol/kg diet (alpha1), 34 mg of alpha-tocopherol/kg diet (alpha2), and 170 mg of alpha-tocopherol/kg diet (alpha3). Wister Kyoto (WKY) rats were used as normal control (N). Blood pressure were recorded from the tail by physiography every other night for the duration of the study period of 3 months. At the end of the trial, animals were sacrificed. The NOS activity in blood vessels was measured by [3H]arginine radioactive assay and the nitrite concentration in plasma by spectrophotometry at wavelength 554 nm using Greiss reagent. Analysis of data was done using Student's t test and Pearson's correlation. The computer program Statistica was used for all analysis. Results of our study showed that for all the three alpha-tocopherol-treated groups, blood pressure was significantly (P < .001) reduced compared to the hypertensive control and maximum reduction of blood pressure was shown by the dosage of 34 mg of alpha-tocopherol/kg diet (C: 209.56 +/- 8.47 mm Hg; alpha2: 128.83 +/- 17.13 mm Hg). Also, NOS activity in blood vessels of SHR was significantly lower than WKY rats (N: 1.54 +/- 0.26 pmol/mg protein, C: 0.87 +/- 0.23 pmol/mg protein; P < .001). Although alpha-tocopherol in doses of alpha1, alpha2, and alpha3 increased the NOS activity in blood vessels, after treatment only that of alpha2 showed a statistical significance (P < .01). Plasma nitrite concentration was significantly reduced in SHR compared to normal WKY rats (N: 54.62 +/- 2.96 mol/mL, C: 26.24 +/- 2.14 mol/mL; P < .001) and accordingly all three groups showed significant improvement in their respective nitrite level (P < .001). For all groups, NOS activity and nitrite level showed negative correlation with blood pressure. It was significant for NOS activity in hypertensive control (r = -0.735, P = .038), alpha1 (r = -0.833, P = .001), and alpha2 (r = -0.899, P = .000) groups. For plasma nitrite, significant correlation was observed only in group alpha1 (r = -0.673, P = .016) and alpha2 (r = -0.643, P = .024). Only the alpha2 group showed significant positive correlation (r = 0.777, P = .003) between NOS activity and nitrite level. In conclusion it was found that compared to WKY rats, SHR have lower NOS activity in blood vessels, which upon treatment with antioxidant alpha-tocopherol increased the NOS activity and concomitantly reduced the blood pressure. There was correlation of lipid peroxide in blood vessels with NOS and nitric oxide, which implies that free radicals may be involved in the pathogenesis of hypertension.

Matched MeSH terms: Hypertension/genetics
Fulltext Striatin Gene Polymorphic Variants Are Associated With Salt Sensitive Blood Pressure in Normotensives and Hypertensives

Gupta T, Connors M, Tan JW, Manosroi W, Ahmed N, Ting PY, et al.

Am J Hypertens, 2017 Dec 08;31(1):124-131.
PMID: 28985281 DOI: 10.1093/ajh/hpx146

BACKGROUND: Understanding the interactions between genetics, sodium (Na+) intake, and blood pressure (BP) will help overcome the lack of individual specificity in our current treatment of hypertension. This study had 3 goals: expand on the relationship between striatin gene (STRN) status and salt-sensitivity of BP (SSBP); evaluate the status of Na+ and volume regulating systems by striatin risk allele status; evaluate potential SSBP mechanisms.
METHODS: We assessed the relationship between STRN status in humans (HyperPATH cohort) and SSBP and on volume regulated systems in humans and a striatin knockout mouse (STRN+/-).
RESULTS: The previously identified association between a striatin risk allele and systolic SSBP was demonstrated in a new cohort (P = 0.01). The STRN-SSBP association was significant for the combined cohort (P = 0.003; β = +5.35 mm Hg systolic BP/risk allele) and in the following subgroups: normotensives, hypertensives, men, and older subjects. Additionally, we observed a lower epinephrine level in risk allele carriers (P = 0.014) and decreased adrenal medulla phenylethanolamine N-methyltransferase (PNMT) in STRN+/- mice. No significant associations were observed with other volume regulated systems.
CONCLUSIONS: These results support the association between a variant of striatin and SSBP and extend the findings to normotensive individuals and other subsets. In contrast to most salt-sensitive hypertensives, striatin-associated SSBP is associated with normal plasma renin activity and reduced epinephrine levels. These data provide clues to the underlying cause and a potential pathway to achieve, specific, personalized treatment, and prevention.

Matched MeSH terms: Hypertension/genetics*
Genetic and interracial aspects of hypertensive toxemia of pregnancy. A prospective study

Gordon H, Huskisson ID, Torrington M, Pannell A, Zackon D

Am J Obstet Gynecol, 1970 May 15;107(2):254-62.
PMID: 5462441
Matched MeSH terms: Hypertension/genetics*
Influence of the Angiotensin II type I receptor gene 1166A > C polymorphism on BP and aortic pulse wave velocity among Malays

Rehman A, Rasool AH, Naing L, Roshan TM, Rahman AR

Ann. Hum. Genet., 2007 Jan;71(Pt 1):86-95.
PMID: 17227479

Angiotensin II type 1 receptor (AGT1R) gene 1166A > C polymorphism has been shown to be associated with essential hypertension and aortic stiffness as measured by carotid femoral pulse wave velocity (PWV). This study was carried out to investigate the association of the 1166A > C polymorphism with blood pressure (BP) and PWV among Malay hypertensive and normotensive subjects. Two hundred and one hypertensive subjects without evidence of cardiovascular (CV) complications and 201 age- and sex-matched normotensive subjects were studied in a cross-sectional design. Blood pressures (BP) and PWV were measured, and 1166A > C genotype was determined by polymerase chain reaction followed by restriction enzyme digestion. The 1166C allele frequency was 7.96% and 7.73% among Malay hypertensive and normotensive subjects, respectively. There was no association of the 1166A > C polymorphism with BP in the hypertensive, normotensive or overall Malay populations. PWV was significantly higher among 1166C allele carriers as compared to non-carriers (10.52 +/- 1.82 vs. 10.15 +/- 1.80, p = 0.040) in the overall population, but not in the hypertensive and normotensive populations separately. In conclusion, the frequency of 1166C polymorphism is similar among Malay hypertensive and normotensive subjects. This polymorphism has no association with BP but may have an influence on PWV in Malays, which needs further investigation.

Matched MeSH terms: Hypertension/genetics
RAS Genetic Variants in Interaction with ACE Inhibitors Drugs Influences Essential Hypertension Control

Heidari F, Vasudevan R, Mohd Ali SZ, Ismail P, Arkani M

Arch Med Res, 2017 Jan;48(1):88-95.
PMID: 28577874 DOI: 10.1016/j.arcmed.2017.03.003

BACKGROUNDS AND AIMS: Essential Hypertension (EH) is a common disorder associated with increased cardiovascular morbidity and mortality in Malaysia. To investigate how genetic polymorphisms of the renin-angiotensin-aldosterone system (RAS) influence EH control with angiotensin-converting enzyme inhibitor drugs (ACEI).
METHODS: A case-control, cross-sectional population-based nested study (n = 142) included hypertensive subjects treated with ACEI drugs, either lisinopril or enalapril (20 mg, once daily) as monotherapy for 24 weeks. In total seven possible polymorphisms of RAS genes were genotyped. The association between those polymorphisms and the changes in blood pressure were observed in the 24 week treatment.
RESULTS: Statistically significant associations of I, G, T, M and G alleles of ACE (I/D, G2350A), AGT (M235T, T175M and G-6A) respectively were observed in essential hypertensive subjects. The decrease in systolic blood pressure and diastolic blood pressure after 24 weeks of treatment of the patients carrying II, GG, and TT genotypes were greater than the groups carrying DD, AA, MM, MM and GG of I/D, G2350A, M235T, T174M and G-6A genotypes respectively. In contrast, No significant difference was observed between renin gene polymorphisms (Bg/I and MboI) and hypertensives.
CONCLUSIONS: Although this study shows a possible association of polymorphisms of RAS genes with the risk of non-control of HT in ACEI-treated patients and indicates the importance of all this system's components in regulating HT, it needs to be replicated in other data sources.

Matched MeSH terms: Hypertension/genetics
Fulltext Angiotensinogen M235T gene variants and its association with essential hypertension and plasma renin activity in Malaysian subjects: a case control study

Say YH, Ling KH, Duraisamy G, Isaac S, Rosli R

BMC Cardiovasc Disord, 2005;5(1):7.
PMID: 15811183

Essential hypertension is a major public health concern worldwide where its prevalence accounts for various cerebrovascular diseases. A common molecular variant of angiotensinogen (AGT), the precursor of potent vasoactive hormone angiotensin II, has been incriminated as a marker for genetic predisposition to essential hypertension in some ethnics. This case-control study was designed not only to determine the association of the AGT M235T gene variants with essential hypertension, but also its relationship to Plasma Renin Activity (PRA) in subjects attending the Health Clinic, Kuala Lumpur, Malaysia.

Matched MeSH terms: Hypertension/genetics*
Fulltext Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia

Ghodsian N, Ismail P, Ahmadloo S, Eskandarian N, Etemad A

Biomed Res Int, 2016;2016:6712529.
PMID: 27413750 DOI: 10.1155/2016/6712529

Background. Atrial natriuretic peptide (ANP) considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID) and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM) status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G) were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR) in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P < 0.05). Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population.

Matched MeSH terms: Hypertension/genetics*
Fulltext Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis

Leong XF, Ng CY, Jaarin K

Biomed Res Int, 2015;2015:528757.
PMID: 26064920 DOI: 10.1155/2015/528757

Hypertension and atherosclerosis are among the most common causes of mortality in both developed and developing countries. Experimental animal models of hypertension and atherosclerosis have become a valuable tool for providing information on etiology, pathophysiology, and complications of the disease and on the efficacy and mechanism of action of various drugs and compounds used in treatment. An animal model has been developed to study hypertension and atherosclerosis for several reasons. Compared to human models, an animal model is easily manageable, as compounding effects of dietary and environmental factors can be controlled. Blood vessels and cardiac tissue samples can be taken for detailed experimental and biomolecular examination. Choice of animal model is often determined by the research aim, as well as financial and technical factors. A thorough understanding of the animal models used and complete analysis must be validated so that the data can be extrapolated to humans. In conclusion, animal models for hypertension and atherosclerosis are invaluable in improving our understanding of cardiovascular disease and developing new pharmacological therapies.

Matched MeSH terms: Hypertension/genetics
Fulltext Analysis of renin-angiotensin aldosterone system gene polymorphisms in Malaysian essential hypertensive and type 2 diabetic subjects

Ramachandran V, Ismail P, Stanslas J, Shamsudin N

Cardiovasc Diabetol, 2009;8:11.
PMID: 19243623 DOI: 10.1186/1475-2840-8-11

The renin-angiotensin aldosterone system (RAAS) plays an important role in regulating the blood pressure and the genetic polymorphisms of RAAS genes has been extensively studied in relation to the cardiovascular diseases in various populations with conflicting results. The aim of this study was to determine the association of five genetic polymorphisms (A6G and A20C of angiotensinogen (AGT), MboI of renin, Gly460Trp of aldosterone synthase and Lys173Arg of adducin) of RAAS genes in Malaysian essential hypertensive and type 2 diabetic subjects.

Matched MeSH terms: Hypertension/genetics*
Candidate gene polymorphisms and their association with hypertension in Malays

Ghazali DM, Rehman A, Abdul Rahman AR

Clin Chim Acta, 2008 Feb;388(1-2):46-50.
PMID: 17977523 DOI: 10.1016/j.cca.2007.10.002

BACKGROUND: Knowledge of candidate gene polymorphisms in a population is useful for a variety of gene-disease association studies, particularly for some complex traits. A single nucleotide variant of the angiotensinogene gene (AGT M235T) and endothelial nitric oxide synthase gene (eNOS G894T) have been associated with hypertension.
METHOD: A cross-sectional study consisting of 200 hypertensives and 198 age- and sex-matched controls was conducted. Subjects involved in this study were pure Malay for 3 generations. The AGT M235T and eNOS G894T polymorphisms were determined by PCR-RFLP method.
RESULTS: The distribution of M235T genotype in the population was 3.5% for MM, 30.4% for MT and 66.1% for TT. No significant difference was observed in genotype (chi(2)=1.30, p=0.52) and allele (chi(2)=0.87, p=0.35) frequencies among the 2 study group. In contrast, the distribution of genotypes for G894T was 74.1% for GG, 24.6% for GT and 1.3% for TT, respectively. Similarly, no significant difference was observed in genotype (chi(2)=0.94, p=0.33) and allele (chi(2)=0.60, p=0.44) frequencies between both study groups.
CONCLUSION: The AGT M235T and eNOS G894T polymorphisms are unlikely to play an important role in the pathogenesis of hypertension in Malays.
Study site: Outpatient clinic, Hospital Universiti Sains Malaysia (HUSM); government clinics, Kelantan, Malaysia.

Matched MeSH terms: Hypertension/genetics*
Fulltext Association between the C34T polymorphism of the AMPD1 gene and essential hypertension in Malaysian patients

Nemati R, Lu J, Ramachandran V, Etemad A, Heidari M, Yahya MJ, et al.

Genet. Mol. Res., 2016 Jun 20;15(2).
PMID: 27323204 DOI: 10.4238/gmr.15026241

The aim of this study was to determine whether C34T, a common polymorphism of the adenosine monophosphate deaminase 1 gene (AMPD1), is associated with essential hypertension (EH). We hypothesize that C34T is associated with the development of EH. A case-control design was used for this study. The DNA was extracted using a commercial kit from the whole blood of 200 patients with hypertension and 200 subjects without hypertension from selected Malaysian ethnicities (Malays, Chinese, and Indians). Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) and agarose gel electrophoresis were used for genotyping. The C34T gene polymorphism of AMPD1 was significantly associated with EH in the Malaysian subjects (P < 0.0001). The genotype frequencies of CC, CT, and TT were 6%, 79%, and 15%, respectively, among hypertensive subjects, while no TT genotypes were observed in the normotensive subjects. Further, the frequency of hypertension was higher among T allele carriers than C carriers (OD = 9.94; 95%CI = 6.851-14.434). There were significant differences in the systolic blood pressure, diastolic blood pressure, and pulse pressure (P ˂ 0.05) between the normotensive and hypertensive Malaysian subjects; we believe those difference were caused by the C34T polymorphism. For the first time in Malaysia, the current study provides evidence that a common polymorphism of the AMPD1 gene (C34T) is strongly associated with EH.

Matched MeSH terms: Hypertension/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: Hypertension/genetics*
Fulltext Association of TNF-α G308A gene polymorphism in essential hypertensive patients without type 2 diabetes mellitus

Ghodsian N, Akhlaghi M, Ramachandran V, Heidari F, Haghvirdizadeh P, Eshkoor SA, et al.

Genet. Mol. Res., 2015 Dec 29;14(4):18974-9.
PMID: 26782547 DOI: 10.4238/2015.December.29.4

This study aims to investigate the effects of tumor necrosis factor alpha (TNF-α) G308A gene polymorphism on essential hypertension (EHT) with or without type 2 diabetes mellitus (T2DM). The project was conducted on buccal epithelial and blood cells for case and control patients, respectively. Epithelial cells were obtained from the inner part of the cheeks. Techniques including DNA extraction, polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLP) were utilized to assess biomarkers of DNA damage. Our results demonstrated significant differences between wild and mutated genotypes among EHT patients without T2DM. We also found a significant association between wild and mutated allele frequencies in EHT patients (P < 0.05). Clinical characteristics between the groups (EHT with or without T2DM and controls) showed statistically significant association (P < 0.05). Overall, we show that G308A polymorphism of the TNF-αgene may be a significant genetic risk factor for EHT without T2DM patients in Malaysia.

Matched MeSH terms: Hypertension/genetics*
Fulltext Natural selection and local adaptation of blood pressure regulation and their perspectives on precision medicine in hypertension

Hoh BP, Abdul Rahman T, Yusoff K

Hereditas, 2019;156:1.
PMID: 30636949 DOI: 10.1186/s41065-019-0080-1

Prevalence of hypertension (HTN) varies substantially across different populations. HTN is not only common - affecting at least one third of the world's adult population - but is also the most important driver for cardiovascular diseases. Yet up to a third of hypertensive patients are resistant to therapy, contributed by secondary hypertension but more commonly the hitherto inability to precisely predict response to specific antihypertensive agents. Population and individual genomics information could be useful in guiding the selection and predicting the response to treatment - an approach known as precision medicine. However this cannot be achieved without the knowledge of genetic variations that influence blood pressure (BP). A number of evolutionary factors including population demographics and forces of natural selection may be involved. This article explores some ideas on how natural selection influences BP regulation in ethnically and geographically diverse populations that could lead to them being susceptible to HTN. We explore how such evolutionary factors could impact the implementation of precision medicine in HTN. Finally, in order to ensure the success of precision medicine in HTN, we call for more initiatives to understand the genetic architecture within and between diverse populations with ancestry from different parts of the world, and to precisely classify the intermediate phenotypes of HTN.

Matched MeSH terms: Hypertension/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: Hypertension/genetics*
Association of insertion/deletion polymorphism of alpha-adrenoceptor gene in essential hypertension with or without type 2 diabetes mellitus in Malaysian subjects

Vasudevan R, Ismail P, Stanslas J, Shamsudin N, Ali AB

Int J Biol Sci, 2008;4(6):362-7.
PMID: 18953403

An insertion/deletion (I/D) polymorphism of Alpha2B-Adrenoceptor (ADRA2B) gene located on chromosome 2 has been studied extensively in related to cardiovascular diseases. The main aim of the present study was to examine the potential association of D allele frequency of I/D polymorphism of ADRA2B gene in Malaysian essential hypertensive subjects with or without type 2 diabetes mellitus (T2DM). This study includes 70 hypertensive subjects without T2DM, 65 hypertensive subjects with T2DM and 75 healthy volunteers as control subjects. Genotyping of I/D polymorphism was performed by conventional PCR method. There was significant difference found in age, body mass index, systolic/diastolic blood pressure and high density lipoprotein cholesterol level between the case and control subjects. DD genotypic frequency of I/D polymorphism was significantly higher in hypertensive subjects (42.84% vs. 29.33%; P-=0.029) and in hypertensive with T2DM subjects (46.15% vs. 29.33%; P=0.046) than control group. D allele frequency was higher in hypertensive group (67.41%) than control subjects (52.67%). However, no significant difference was found between the three genotypes of I/D polymorphism of ADRA2B gene and the clinical characteristics of the subjects. The result obtained in this study show D allele of ADRA2B gene was associated with essential hypertension with or without T2DM in Malaysian subjects.

Matched MeSH terms: Hypertension/genetics*
Mutational analysis of CYP2C8 in hypertensive patients using denaturing high performance liquid chromatography

Teh LK, Zahri MK, Zakaria ZA, Ismail R, Salleh MZ

J Clin Pharm Ther, 2010 Dec;35(6):723-8.
PMID: 21054465 DOI: 10.1111/j.1365-2710.2009.01146.x

CYP2C8 is involved in the cytochrome P450 (CYP) epoxygenase pathway. Arachidonic acid metabolites such as epoxyeicosatrienenoic acids and hydroxyeicosatetrenoic acids, produced may have a role in hypertension. We aimed to develop a medium through-put method for screening samples of known and new mutations of CYP2C8 using denaturing high performance liquid chromatography (DHPLC).

Matched MeSH terms: Hypertension/genetics*
Fulltext Novel Association of WNK4 Gene, Ala589Ser Polymorphism in Essential Hypertension, and Type 2 Diabetes Mellitus in Malaysia

Ghodsian N, Ismail P, Ahmadloo S, Heidari F, Haghvirdizadeh P, Ataollahi Eshkoor S, et al.

J Diabetes Res, 2016;2016:8219543.
PMID: 27314050 DOI: 10.1155/2016/8219543

With-no-lysine (K) Kinase-4 (WNK4) consisted of unique serine and threonine protein kinases, genetically associated with an autosomal dominant form of hypertension. Argumentative consequences have lately arisen on the association of specific single nucleotide polymorphisms of WNK4 gene and essential hypertension (EHT). The aim of this study was to determine the association of Ala589Ser polymorphism of WNK4 gene with essential hypertensive patients in Malaysia. WNK4 gene polymorphism was specified utilizing mutagenically separated polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method in 320 subjects including 163 cases and 157 controls. Close relation between Ala589Ser polymorphism and elevated systolic and diastolic blood pressure (SBP and DBP) was recognized. Sociodemographic factors including body mass index (BMI), age, the level of fasting blood sugar (FBS), low density lipoprotein (LDL), and triglyceride (TG) in the cases and healthy subjects exhibited strong differences (p < 0.05). The distribution of allele frequency and genotype of WNK4 gene Ala589Ser polymorphism showed significant differences (p < 0.05) between EHT subjects with or without type 2 diabetes mellitus (T2DM) and normotensive subjects, statistically. The WNK4 gene variation influences significantly blood pressure increase. Ala589Ser probably has effects on the enzymic activity leading to enhanced predisposition to the disorder.

Matched MeSH terms: Hypertension/genetics*

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