Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The deletion of thiazide-sensitive Na-Cl cotransporter ( TSC, SLC12A3) causes Gitelman's syndrome characterized by low blood pressure, while deletions of the WNK1 ( PRKWNK1) and WNK4 ( PRKWNK4) genes cause familial hypertension known as pseudohypoaldosteronism type II. Recent studies have revealed that cell surface expression of TSC is regulated by WNK1 and WNK4. We hypothesized that molecular variations in TSC, WNK1, and WNK4 could lead to an increased morbidity of hypertension. We identified 52, 35, and 21 polymorphisms in Japanese hypertensives by sequencing the entire coding regions of TSC, WNK1 and WNK4, respectively. Twenty-one representative polymorphisms were genotyped in 1,818 Japanese individuals (771 subjects with hypertension and 1,047 controls) randomly sampled in Suita city. The results indicated that the systolic blood pressure in men with the CT+TT genotype in WNK4 C14717T was 3.1 mmHg higher than those with the CC genotype ( p=0.042) after adjustment with confounding factors such as age, BMI, hyperlipidemia, diabetes mellitus, antihypertensive drug use, smoking, and drinking. Multivariate logistic regression analysis (with adjustment for the same parameters) in men revealed that the odds ratio for the presence of hypertension of the CT+TT genotype in C14717T to the CC genotype was 1.62 ( p=0.010, 95% confidence interval, 1.12-2.33). Association of TSC and WNK1 with hypertension was not observed. In conclusion, our study suggests the possible involvement of WNK4 in essential hypertension in a Japanese general population.
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PMID:Identification of 108 SNPs in TSC, WNK1, and WNK4 and their association with hypertension in a Japanese general population. 1530 83

The response of blood pressure to thiazide diuretics (TZDs) differs among individuals. The prediction of the antihypertensive effect of TZDs is important for realizing individualized therapy in the management of hypertension. The aim of this study was to identify the single nucleotide polymorphisms (SNPs) susceptible to the antihypertensive effect of TZDs, particularly focusing on genes related to water-electrolyte absorption in the kidney. Seventy-six outpatients (mean age, 65.4+/-9.0 years) with essential hypertension (EHT) taking TZDs were retrospectively assessed. We defined as responders (R) those whose mean blood pressure was lowered by more than 5 mmHg after the use of TZDs. Forty-eight SNPs in 17 genes (ADD1, GNB3, TSC [SLC12A3], MLR [NR3C2], NCX1 [SLC8A1], WNK1, WNK4, AGT, ACE, AT1 [AGTR1], CYP11B2, ADRB1, ADRB2, ADRB3, ADRA1A, ADRA1B, ADRA2A) were genotyped in the 76 patients. The SNPs in TSC, MLR, NCX1, WNK1, and WNK4 were identified by direct sequencing and those with minor frequencies of greater than 5% were genotyped in this study. The comparison of polymorphism prevalence between R and non-responders (NR) showed significant differences in TSC C1784T (C allele vs. T allele, odds ratio (OR)=3.81, p =0.016, confidence interval (CI): 1.25-11.63) and ADRB3 T727C (Trp64Arg) (T allele vs. C allele, OR=4.59, p =0.005, CI: 1.54-13.68). The blood pressure (BP) in patients homozygous for the major alleles of both TSC C1784T and ADRB3 T727C were significantly reduced by TZD treatment; however, the BP in those homozygous for the minor allele and heterozygous (TSC C1784T: TT+CT; ADRB3 T727C: CC+CT) for both SNPs were not significantly changed after TZD treatment. Both newly detected TSC C1784T and ADRB3 T727C are gene polymorphisms susceptible to the antihypertensive effect of TZDs in patients with EHT. Thus, the prediction of BP reduction by TZDs may be possible by evaluating these two SNPs.
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PMID:The thiazide-sensitive Na(+)-Cl(-) cotransporter gene, C1784T, and adrenergic receptor-beta3 gene, T727C, may be gene polymorphisms susceptible to the antihypertensive effect of thiazide diuretics. 1582 64

Thiazide-sensitive Na-Cl cotransporter (TSC, SLC12A3) is located on chromosome 16q13 and is expressed specifically in the renal distal convoluted tubule, where it mediates the reabsorption of Na+ and Cl-. Mutation of TSC is known to be responsible for Gitelman's syndrome, an autosomal recessive renal tubular disorder characterized by low blood pressure due to renal sodium wasting, hypokalemia, metabolic alkalosis, hypomagnesemia and normocalcemic hypocaliuria. We assessed mutational analysis of the TSC gene in 35 patients with Gitelman's syndrome. We found 16 missense mutaions, insertion of 18bp in the 6th exon, deletion of C in the 9th exon and deletion of C in the 16th exon. These results suggest that there is no mutational hot spot in the TSC gene. These 19 mutations include eight novel mutations: R261C, N406H, A523T, M672I, R1009Q, N1014K, deletion of C in the 9th exon and deletion of C in the 16th exon. The eight novel mutations might be responsible for impairment of NaCl reabsorption leading to the principal clinical features of Gitelman's syndrome in these patients. These mutations could bring new insights into genotype-phenotype correlations among the hypokalemic tubulopathies. Recently, genome-wide association studies, using SNPs to identify loci involved in susceptibility to common diseases, showed that the TSC gene may contribute to genetic susceptibility to diabetic nephropathy in Japanese. In addition, substitution of Arg904 to Gln in the TSC gene has been reported to predispose essential hypertension in Swedish and Japanese populations. Further studies are needed to clarify the possible associations of the TSC gene with common diseases.
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PMID:[Clinical significance of thiazide-sensitive Na-Cl cotransporter gene by mutational analysis]. 1751 Dec 64

Hypertension in children is not as frequent as adults. In addition, most of the times, we encounter secondary hypertension rather than essential hypertension in children. This demands careful history taking, physical examination, and laboratory and imaging investigations to find the underlying cause. Here, a boy with tuberous sclerosis is reported who presented with hypertension and abdominal pain associated with bilateral renal cystic disease.
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PMID:Tuberous sclerosis with hypertension and abdominal pain in a child. 2062 17

Although there have been several studies investigating a possible association between essential hypertension and TSC gene Arg904Gln polymorphisms, the results have been inconsistent. We conducted a meta-analysis of four case-control studies (one study in Europe and three studies in Asia), including 1811 essential hypertension cases and 1381 controls. The pooled results showed no significant associations between any of these polymorphisms and essential hypertension (allele Arg vs allele Gln: odds ratio (OR) = 0.94, 95% confidence interval (95%CI) = 0.70-1.27), additive genetic model (Arg/Arg vs Gln/Gln: OR = 0.98, 95%CI = 0.43-2.23), dominant genetic model (Arg/Arg + Arg/Gln vs Gln/ Gln: OR = 0.97, 95%CI = 0.43-2.21), and recessive genetic model (Arg/ Arg vs Arg/Gln + Gln/Gln: OR = 1.03, 95%CI = 0.45-2.35). Based on the results of our meta-analysis, we conclude that the TSC gene Arg904Gln polymorphism is not associated with essential hypertension risk.
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PMID:Lack of an association between TSC gene Arg904Gln polymorphisms and essential hypertension risk based on a meta-analysis. 2307 45