Associations between aldosterone synthase gene polymorphism and the adrenocortical function in males

Hautanen, Aarno; LANKINEN, L.; Kupari, Markku; Jänne, Olli A.; Adlercreutz, Herman; Nikkila, Heli; White, Perrin C.

doi:10.1046/j.1365-2796.1998.00308.x

Cited by 88 publications

(70 citation statements)

References 19 publications

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“…In keeping with the results of earlier studies, the associations of the CYP11B2 C-344T polymorphism with BP remain inconclusive. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] In addition, our results were not consistent with previous reports indicating that BP elevation was sensitive in elderly subjects with the TT genotype. 20,21 Furthermore, we suggested that the association of the CC genotype with CRP was consistent with previous reports describing the association of the genotype with cardiac structures and atherosclerosis as discussed above, 17,34 whereas some apparent contradictory associations between the genotype and atherosclerosis, including cardiac structure and coronary artery diseases, have been shown in previous studies.…”

Section: Discussioncontrasting

confidence: 99%

“…1,2 One of the polymorphisms of aldosterone synthase (CYP11B2), rs1799998, which is located À344 bp upstream and consistent with either T or C, may influence the cardiovascular system through the effects of aldosterone, because the C allele binds to the steroidogenic factor-1 (SF-1) site five times stronger than does the T allele. 3 An overview of published studies suggests a higher frequency of hypertension or increase in blood pressure (BP) in subjects with the T allele or TT genotype as compared with that in subjects with the C allele or CC genotype, [4][5][6][7][8][9][10] although several studies have reported the opposite association 11,12 or the absence of any association. [13][14][15][16][17][18][19] Thus, the associations remain controversial.…”

Section: Introductionmentioning

confidence: 99%

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Aldosterone synthase (CYP11B2) C-344T polymorphism affects the association of age-related changes of the serum C-reactive protein

et al. 2010

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Aldosterone participates in vascular and myocardial inflammation either directly or indirectly through blood pressure (BP). Aldosterone synthase (CYP11B2) C-344T polymorphism may influence the severity of systemic inflammation. A total of 398 Japanese Americans (152 men and 246 women, age 19-92 years) from the Hawaii-Los Angeles-Hiroshima study were enrolled. BP and serum levels of C-reactive protein (CRP) were measured, and the CYP11B2 C-344T polymorphism, rs1799998, was determined. No influence of the polymorphism on baseline characteristics such as systolic, diastolic and mean BP, pulse pressure or serum CRP levels was observed. In all genotypes, systolic BP showed a significantly positive correlation with age (TT (n¼178): r¼0.283, Po0.001; TC (n¼164): r¼0.213, P¼0.006; and CC (n¼56): r¼0.289, P¼0.031). However, the regression coefficients of systolic BP with age were not different across genotypes. According to the results of univariate and multivariate analyses with adjustment for BP, the serum CRP level increased with age only in subjects with the CC genotype (P¼0.027 and P¼0.004, respectively), and elevation of serum CRP was mainly observed in the elderly population (aged X60 years). Moreover, the regression coefficient of CRP levels with age was significantly steeper in subjects with the CC genotype than in those with the TC or TT genotype (P¼0.028). The CC genotype of the CYP11B2 C-344T polymorphism was associated with an age-dependent increase in the serum CRP level independent of BP, and may contribute to a cardiovascular phenotype by promoting vascular inflammation.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Aldosterone synthase (CYP11B2) C-344T polymorphism affects the association of age-related changes of the serum C-reactive protein

et al. 2010

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“…8 The mechanism of the association is not known, but may involve an effect of genotype on the activity of the CYP11B2 gene and consequent differences between genotypes on plasma and tissue aldosterone activity. However, the data relating CYP11B2 variants and plasma or urine aldosterone levels are conflicting, with some observing opposite effects of the T-344C polymorphism, 5,27,28 while others have found no effect. 10 Thus, the mechanism of the association between variants at the CYP11B2 locus and anatomical measures of cardiac size remains to be established.…”

Section: Discussionmentioning

confidence: 99%

Measured haplotype analysis of the aldosterone synthase gene and heart size

et al. 2003

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Gene-association studies of heart size and the aldosterone synthase (CYP11B2) gene have produced inconsistent results, possibly because of limitations in the sample size and/or the number and location of the polymorphisms. An analysis of six polymorphisms spanning 6 kb of the CYP11B2 gene in Caucasian British families revealed a limited number of haplotypes because of strong linkage disequilibrium over this small region. The genotype and haplotype information was used in an association study involving 955 members of 229 families phenotyped for echocardiographic measures of heart size. In a mixed effects linear modelling analysis, the G5937C polymorphism was associated with cardiac wall thickness (P ¼ 0.02), and the intron conversion and A4550C polymorphisms were associated with left ventricular cavity size (P ¼ 0.02 and 0.002, respectively). Measured haplotype analyses confirmed the association of alleles at the intron conversion and G5937C polymorphisms with cardiac wall thickness (P ¼ 0.02), and alleles at the intron conversion polymorphism with left ventricular cavity size (P ¼ 0.04). The polymorphisms contributed to 2.0 -3.4% of the variability in these traits. In summary, genetic polymorphisms at the CYP11B2 gene make a small contribution to quantitative variation in echocardiographic measures of heart size. These results point to the importance of analysing the full extent of genetic variation that captures the haplotype structure of a locus in gene association studies.

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“…Aldosterone synthase genotypes and fasting glucose levels by ethnicity, geographical origin, medication status, and within siblingships gene in in vitro experiments (25). This SNP was associated also with plasma and urinary aldosterone levels (26)(27)(28)(29)(30). Linkage disequilibrium between the T-344C and Lys-173͞Arg SNPs, however, was not examined in these studies, therefore raising the possibility that, in fact, the Lys-173͞Arg SNP (or another undetected polymorphism in this gene) was causatively associated with differences in aldosterone levels in these studies.…”

Section: Discussionmentioning

confidence: 90%

Genetic variation in aldosterone synthase predicts plasma glucose levels

Ranade

Risch

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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The mineralocorticoid hormone, aldosterone, is known to play a role in sodium homeostasis. We serendipitously found, however, highly significant association between single-nucleotide polymorphisms in the aldosterone synthase gene and plasma glucose levels in a large population of Chinese and Japanese origin. Two polymorphisms-one in the putative promoter (T-344C) and another resulting in a lysine͞arginine substitution at amino acid 173, which are in complete linkage disequilibrium in this population-were associated with fasting plasma glucose levels (P ‫؍‬ 0.000017) and those 60 (P ‫؍‬ 0.017) and 120 (P ‫؍‬ 0.0019) min after an oral glucose challenge. A C͞T variant in intron 1, between these polymorphisms, was not associated with glucose levels. Arg-173 and -344C homozygotes were most likely to be diabetic [odds ratio 2.51; 95% confidence interval (C.I.) 1.39 -3.92; P ‫؍‬ 0.0015] and have impaired fasting glucose levels (odds ratio 3.53; 95% C.I. 2.02-5.5; P ‫؍‬ 0.0000036). These results suggest a new role for aldosterone in glucose homeostasis.H ypertension affects 15-50% of the adult population and is one of the major risk factors for stroke, myocardial infarction, and renal disease. Despite intense effort, our understanding of heritable factors in the etiology of hypertension is rather poor. Twin, adoption, and epidemiologic studies indicate that variation in blood pressure (BP) is genetically determined to some extent (1-3). Insulin resistance, defined as the sluggish uptake of glucose by peripheral tissue in the presence of normal or elevated levels of insulin, is frequently associated with hypertension (4). One of the goals of the Stanford, Asia, and Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) study is to identify predisposing genes for essential hypertension and insulin resistance.To maximize our chances of finding susceptibility genes for these diseases, we took several steps. First, in an attempt to reduce genetic heterogeneity, we focused on a relatively homogeneous population of Chinese and Japanese descent. Second, we sampled subjects from tails of the systolic or diastolic BP distributions-the affected hypertensives were recruited from the upper 20% of the distribution, whereas the unaffected ''low-normotensive'' individuals had BP readings in the lower 30% of the distribution (5). Third, because recent theoretical work suggests that association studies might be adequately powerful to detect susceptibility loci that have a modest effect on the phenotype (6), we began candidate gene studies by testing specific variants in genes that might, for biological reasons, be expected to be involved in BP regulation or glucose homeostasis for association with hypertension or insulin resistance.The mineralocorticoid hormone, aldosterone, by determining the amount of sodium and water reabsorbed by the kidney, plays a key role in regulating BP (7). Indeed, mutations in the aldosterone synthase gene or in the receptor for the hormone can cause Mendelian forms of hypertension and hypotension ...

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Associations between aldosterone synthase gene polymorphism and the adrenocortical function in males

Abstract: Polymorphisms in or near the aldosterone synthase gene are associated with variations in aldosterone and 11-deoxycortisol production in males. This may modulate the activity of the renin-angiotensin system and thereby contribute to blood pressure regulation.

Cited by 88 publications

References 19 publications

Aldosterone synthase (CYP11B2) C-344T polymorphism affects the association of age-related changes of the serum C-reactive protein

Aldosterone synthase (CYP11B2) C-344T polymorphism affects the association of age-related changes of the serum C-reactive protein

Measured haplotype analysis of the aldosterone synthase gene and heart size

Genetic variation in aldosterone synthase predicts plasma glucose levels

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