Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are ethnic differences in the prevalence and severity of hypertension and asthma and in beta-2 adrenergic receptor (BAR2)-mediated vascular responses. Two common polymorphisms of the human BAR2, Arg16 to Gly and Gln27 to Glu, are associated with alterations in BAR2 response, both in vitro and in vivo. Ethnic differences in disease manifestations and responses to treatment may be explained by the altered frequency of BAR2 polymorphisms. To determine the relative frequencies of the Arg16 to Gly and Gln27 to Glu BAR2 polymorphisms in different ethnic groups we studied 415 (123 African-American, 188 Caucasian-American and 104 Chinese) healthy individuals. There was a marked interethnic difference in the frequency of the BAR2 polymorphisms among the ethnic groups. The Glu27 allele was more frequent in Caucasian-American (34.8%) than in African-American individuals (20.7%) (P = 0.0001) and much less frequent in Chinese individuals (7.2%) (P = 0.0001 versus African-American or Caucasian-American). The homozygous Glu27 genotype was more frequent in Caucasian-American (15.4%) than African-American individuals (4.9%) (P = 0.003) and was not observed in Chinese. The Gly16 allele (54.3% versus 41.3%) and homozygous genotype (35.1% versus 18.3%) were more common in Caucasian-American than Chinese individuals (P = 0.003 for both). There is a marked ethnic difference in the frequency of these two common BAR2 polymorphisms among African-American, Caucasian-American and Chinese individuals, with a markedly reduced frequency of the Glu27 polymorphism, the polymorphism associated with resistance to desensitization and increased BAR2 responses, in African-American and Chinese individuals. Such ethnic genotypic differences may explain previously observed alterations in the response to the BAR agonists in different ethnic groups.
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PMID:Frequency of functionally important beta-2 adrenoceptor polymorphisms varies markedly among African-American, Caucasian and Chinese individuals. 1078 Feb 71

A genetic linkage study of young-onset hypertension was performed on data from 59 nucleus families of Han Chinese residing in Taiwan. Thirty seven microsatellite markers near 18 hypertension candidate genes were genotyped. In a nonparametric identity-by-descent sibpair analysis, a positive linkage signal (defined as P<0.05) was found for four microsatellite markers, viz., D1S1612 (P=0.0162), D1S547 (P=0.0263), D8S 1145 (P= 0.0284), and D17S2193 (P=0.0256), which were located near genes for atrial natriuretic peptide (NPPA)/glucose transporter 5 (SLC2A5), angiotensinogen (AGT), lipoprotein lipase (LPL), and angiotensin-conveting enzyme (DCP1), respectively. Marker D5S1480 located near beta-2-adrenergic receptor (ADRB2) had a borderline P value (P=0.0785) for the positive signal. Comprehensive genotyping with further markers in these regions is underway to confirm whether these genes are linked to young-onset hypertension.
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PMID:Linkage analysis with candidate genes: the Taiwan young-onset hypertension genetic study. 1107 81

Significant evidence has been provided for the pathophysiological involvement of the beta(2)-adrenergic receptor (ADRB2) in hypertension. Among ADRB2 polymorphisms identified to date, 2 amino acid substitutions, Arg16Gly and Gln27Glu, and a promoter variant, T-47C, are considered functionally important. In particular, Arg16Gly was shown to be associated with hypertension in black and white subjects. To investigate the relevance of ADRB2 polymorphisms to hypertension, we undertook an extensive association study in a Japanese population. An association was tested in 2 ways. First, a case-control study was conducted in 842 hypertensive and 633 normotensive subjects. In addition to the overall comparison between case and control groups, each was stratified by body mass index and compared with an independent panel of 525 diabetic subjects. Second, ANOVA and multivariate analyses were performed to test the significance of an association between ADRB2 genotype and the level of blood pressure within the entire population except for 395 subjects who had been under treatment for hypertension. Although no significant association was observed for Arg16Gly and T-47C, 2 analytical methods indicated a marginal association (P:=0.01 to 0.04) between the Glu27 variant and lower blood pressure levels. Given such a normotensive propensity, the odds ratio for Glu27 versus Gln27 allele frequencies was estimated to be 0.74, with a wide confidence interval (95% CI, 0.55 to 0.99) reflecting the low Glu27-allele frequency (6% to 8%) in Japanese. There were no apparent confounding influences of obesity and diabetes on the postulated association. Our data suggest that 3 ADRB2 polymorphisms tested are unlikely to confer principal genetic susceptibility for hypertension in the Japanese population. However, further investigation is warranted to clarify the relevance of ADRB2 polymorphisms to blood pressure regulation.
Hypertension 2001 Feb
PMID:Association analysis of beta(2)-adrenergic receptor polymorphisms with hypertension in Japanese. 1123 Feb 87

Beta2-adrenoceptor (beta2-ADR)-mediated vasodilatation decreases vascular reactivity and blood pressure (BP) and chromosome 5 where its gene (ADRB2R) resides and shows linkage to hypertension (HT). A Gln27Glu ADRB2R variant confers resistance to agonist-induced desensitization and enhanced vasodilator response to isoprenaline. Therefore, we carried out a case-control study in a cohort of HT and normotensive (NT) Anglo-Celtic Australian white subjects whose parents had a similar BP status as the subjects. Glu27 frequency was 0.41 in 108 HT and 0.42 in 141 NT (chi2 = 0.05, P = .82). Within the HT group, the Glu27 allele was more prevalent in 61 subjects who were overweight (body mass index [BMI] > or = 25 kg/m2) compared with 41 who were lean (BMI <25 kg/m2); ie, 0.49 v 0.31, respectively (chi2 = 6.4, P = .012). Furthermore, Glu27 tracked with elevation in BMI in these subjects: 24 +/- 4 kg/m2, 27 +/- 5 kg/m2, and 28 +/- 5 kg/m2 for Gln/Gln, Gln/Glu, and Glu/Glu, respectively (P = .0058 by one-way ANOVA). Thus, the Gln27Glu beta2-ADR variant is excluded in HT, but might influence body weight.
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PMID:Association of beta2-adrenoceptor Gln27Glu variant with body weight but not hypertension. 1177 27

Previous studies suggest that variants of the beta(2)-adrenergic receptor (ADRB2) may differently affect functional responses to adrenergic stimulation, thereby possibly modulating cardiovascular and metabolic phenotypes. We examined the hypothesis that G/R16 and Q/E27 polymorphism of ADRB2, or their haplotypes, may modulate blood pressure, cardiovascular structure, and function or metabolic cardiovascular risk factors in the general population. We examined a random sample of the general population (n=571; age, 35 to 64 years). Neither clinic nor 24-hour ambulatory blood pressure was significantly associated with ADRB2 genotypes in the overall population. Cardiac structure and function were also not influenced by ADRB2 polymorphism. After adjustment for potential confounders, association of the R16 allele with higher systolic blood pressure was observed in the subgroup of younger people (below age of 50 years). Haplotype analysis showed that higher blood pressure values were more specifically associated with the presence of R16-Q27. Younger people carrying the R16-Q27 haplotype also showed a trend toward lower heart rate, higher BMI, lower glycemia, and higher trygliceridemia, which is consistent with the hypothesis of a genetic predisposition to reduced cardiovascular and metabolic response to ADRB2 stimulation. This study does not provide evidence of a major role of ADRB2 gene variability in blood pressure modulation. However, association of ADRB2 polymorphism with cardiovascular and metabolic effects can be observed in younger subjects, before the development of age-related decline of ADRB2-mediated activity. Our study emphasizes the necessity of taking into account (patho)-physiological changes related to aging (in this case, decreased efficiency of ADRB2 signaling) when analyzing phenotypic effects of genetic variants.
Hypertension 2003 Feb
PMID:Beta(2)-adrenergic receptor gene polymorphism, age, and cardiovascular phenotypes. 1257 8

Allelic variation at multiple genetic loci may contribute to hypertension. Since autonomic/sympathetic dysfunction may play an early, pathogenic, heritable role in hypertension, we evaluated candidate loci likely to contribute to such dysfunction, including catecholamine biosynthetic enzymes, catecholamine transporters, neuropeptides, and adrenergic receptors. Since chromosomal locations and physical map positions of many of these loci had not yet been identified, we used the GeneBridge4 human/hamster radiation (somatic cell) hybrid library panel (resolution approximately 1 to approximately 1.5 Mb), along with specifically designed oligonucleotide primers and PCR (200-400 bp products) to position these loci in the human genome. Primers were designed from sequences outside the coding regions (3'-flanking or intronic segments) to avoid cross-species (hamster) amplification. Chromosomal positions were assigned in cR (centi-Ray) units ( approximately 270 Kbp/cR(3000) for GeneBridge 4). A total of 13 loci were newly assigned chromosomal positions; of particular interest was a cluster of adrenergic candidate loci on chromosome 5q (including ADRB2, ADRA1A, DRD1, GPRK6, and NPY6R), a region harbouring linkage peaks for blood pressure. Such physical map positions will enable more precise selection of polymorphic microsatellite and single nucleotide polymorphism markers at these loci, to aid in linkage and association studies of autonomic/sympathetic dysfunction in human hypertension.
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PMID:Physical mapping of autonomic/sympathetic candidate genetic loci for hypertension in the human genome: a somatic cell radiation hybrid library approach. 1275 4

Polymorphisms in the beta2 adrenergic receptor (ADRB2), in particular G16R, Q27E, and T164I, have been implicated in the pathogenesis of cardiovascular and metabolic phenotypes. However, no prospective, genetic-epidemiological data are available on the risk of cardiovascular disease associated with these variants. Using DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we evaluated the G16R, Q27E, and T164I polymorphisms among 523 individuals who subsequently developed myocardial infarction and among 2092 individuals who remained free of reported cardiovascular events during follow-up. The haplotype frequency distribution was significantly different among cases and controls (chi(2)(7d.f.) = 20.92, P = 0.0039). Haplotype-based logistic regression, adjusting for age, smoking, and randomized treatment group, indicated that G16-Q27-I164 (odds ratio 0.178, 95% C.I. 0.043-0.737, P = 0.017) and (non-G16-Q27)-T164 (odds ratio 1.235, 95% C.I. 1.031-1.480, P = 0.022) haplotypes were significantly associated with altered risk of myocardial infarction. These findings remained after further adjustment for BMI, history of hypertension, and presence or absence of diabetes. In conclusion, variation in haplotype frequencies for the beta2 adrenergic receptor gene was found to be associated with risk of myocardial infarction.
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PMID:Haplotype analysis of the beta2 adrenergic receptor gene and risk of myocardial infarction in humans. 1552 Feb 58

The aim of this study was to investigate the association between polymorphisms in the beta(2)-adrenergic receptor gene (ADRB2) (-47C/T, Arg16/Gly, Gln27/Glu) and stage-2 hypertension in northern Han Chinese. We recruited 503 individuals with stage-2 hypertension and 504 age-, gender-, and area-matched controls from the International Collaborative Study of Cardiovascular Disease in Asia. Genotyping was performed using PCR-RFLP. Logistic regression analyses revealed that carriers of the Gly16 allele had a significantly higher odds ratio (OR) for hypertension, while carriers of the Glu27 allele had a significantly lower OR. In multivariate linear regression analyses, the Arg16/Gly and Gln27/Glu genotypes were significantly associated with systolic blood pressure level (p = 0.004 and p < 0.001, respectively). In haplotype analyses, we found the frequency of haplotypes composed of the Gly16 and Gln27 alleles was significantly higher, whereas the frequency of haplotypes composed of the Arg16 and Glu27 alleles was significantly lower, in hypertensives compared to their controls (both p = 0.001). These results indicate that the Gly16 and Gln27 alleles of the ADRB2 gene confer an increased risk for stage-2 hypertension in this northern Han Chinese population.
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PMID:beta2-Adrenergic receptor gene variations associated with stage-2 hypertension in northern Han Chinese. 1563 26

Insulin resistance is a determinant of blood pressure variation and risk factor for hypertension. Because insulin resistance and blood pressure cosegregate in Mexican American families, we thus investigated the association between variations in 9 previously reported hypertension genes (ACE, AGT, AGTRI, ADDI, NPPA, ADDRB2, SCNN1A, GNB3, and NOS3) and insulin resistance. Families were ascertained via a coronary artery disease proband in the Mexican American Coronary Artery Disease Project. Individuals from 100 Mexican American families (n=656) were genotyped for 14 polymorphisms in the 9 genes and all adult offspring and offspring spouses were phenotyped for insulin sensitivity by hyperinsulinemic euglycemic clamp (n=449). AGT M235T and NOS3 A(-922)G and E298D polymorphisms were significantly associated with insulin sensitivity (P=0.018, 0.036, 0.039) but were not significant after adjusting for body mass index. ADD1 G460W was associated with insulin sensitivity only after adjusting for body mass index. The NPPA T2238C and SCNN1A A663T were associated with decreased fasting insulin levels after adjusting for body mass index (P=0.015 and 0.028). In conclusion, AGT, NOS3, NPPA, ADRB2, ADD1, and SCNN1A may well be genetic markers for insulin resistance, and adiposity was a potential modifier for only some gene/trait combinations. Our data support the hypothesis that genes in the blood pressure pathway may play a role in insulin resistance in Mexican Americans.
Hypertension 2005 Apr
PMID:Hypertension genes are genetic markers for insulin sensitivity and resistance. 1569 55

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


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