Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Adducins”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed2000

Association between the alpha-adducin gene and hypertension in the HyperGEN Study.

This report from the HyperGEN Study, one of four networks participating in the NHLBI-sponsored Family Blood Pressure Program, presents the results of an association study based on 822 white and 572 black subjects (cases and controls) participating in the HyperGEN Network from five geographically diverse field centers. All cases met the Joint National Committee on Detection and Treatment of High Blood Pressure (JNC VI) criteria for hypertension (Stage I or higher). Each subject was clinically examined for risk factors for hypertension as well as genotyped for the point mutation Gly460Trp at the alpha-adducin locus on chromosome 4p. In the white group, the prevalence of genotypes with one or more Trp alleles was 26% in normotensives, versus 33% in hypertensives randomly selected from the population, and 39% among the multiply affected hypertensive sibships. Overall, in whites, the Trp allele significantly increased the odds of hypertension (P = .0056), with an odds ratio (OR) of 1.73 (95% confidence interval [CI] = 1.17, 2.54). The alpha-adducin gene remained a significant independent predictor of hypertension in a multivariate logistic model even after correcting for other risk factors for hypertension, including gender, age, body mass index (BMI), smoking, LDL cholesterol, triglycerides, urine sodium (Na), and urine potassium (K), (OR = 1.55, 95% CI = 1.03, 2.34). Through the use of regression trees, several gene-by-environment interactions were implicated, suggesting that alpha-adducin appears to be a particularly important risk factor (OR = 4.2) for older (age > 60.5 years), less lean (BMI < 25.8 kg/m2) subjects with moderately high triglycerides (between 145.5 and 218.5 mg/dL). In the black group, the relationship was less clear. Overall, it was protective against hypertension. The prevalence of genotypes with one or more Trp alleles was 24% among normotensive versus 11% in hypertensive black subjects randomly selected from the population, and 13% among multiply affected hypertensive sibships, resulting in an OR of 0.48 (P = .0231; 95% CI = 0.25, 0.90). However, the Trp genotype was no longer a significant independent predictor of hypertension risk in the multivariate logistic model (OR = 0.79; 95% CI = 0.37, 1.67), suggesting that it may be operating through one or more of these other factors. Thus, we conclude that the alpha-adducin gene is a significant, independent risk factor for hypertension in whites, but not in blacks, and may play a particularly important role for subjects with certain constellations of other risk factors.

Alleles↗
PubMed1996

Differential distributions of two adducin-like protein isoforms in the Drosophila ovary and early embryo.

Adducin is a cytoskeletal protein that can function in vitro to bundle F-actin and to control the assembly of the F-actin/spectrin cytoskeletal network. The Drosophila Adducin-like (Add) locus (also referred to as hu-li tai shao (hts)) encodes a family of proteins of which several are homologous to mammalian adducin (Ding et al., Proc. Natl. Acad. Sci. USA 90, 2512-16, 1993; Yue & Spradling, Genes Dev. 6, 2443-54, 1992). We report the identification of two novel adducin isoforms: a 95 x 10(3) Mr form (ADD-95) and an 87 x 10(3) Mr form (ADD-87). We present a detailed analysis of the distribution patterns of ADD-95 and ADD-87 during oogenesis and embryogenesis. The isoforms are co-expressed in several cell- and tissue-types; however, only ADD-87 is present in mid- to late-stage oocytes. ADD-87 is present throughout the oocyte cortex at stages 9 and 10 of oogenesis but is detectable only at the anterior pole from stage 11 onward, correlated with localisation of Add-hts mRNA first to the cortex and then to the anterior pole of the oocyte. ADD-87 co-localises with F-actin and spectrin in the cortex of the oocyte through stage 10 of oogenesis, consistent with a possible role in cytoskeletal assembly or function predicted by mammalian studies.

Actins↗
PubMed2000

Association of the alpha-adducin polymorphism with blood pressure and risk of myocardial infarction.

Genetic variation in adducin, a protein associated with the inner leaflet of the plasma membrane, may be in part responsible for salt-sensitive hypertension. In the Netherlands, 560 men who survived a myocardial infarction and 646 men who had undergone an orthopaedic intervention participated in a case-control study. In men in this study, the alpha-adducin polymorphism was not associated with the risk of myocardial infarction either among those with or among those without a clinical history of hypertension. In a cross-sectional analysis of blood pressure data from the controls, the alpha-adducin polymorphism was associated neither with self-reported hypertension (OR = 0.78, 95% CI = 0.51-1.19) nor with mean levels of systolic or diastolic blood pressure. Additional studies in other populations are needed to assess the contribution of alpha-adducin to high blood pressure and cardiovascular risk.

Aged↗
PubMed1994

Two point mutations within the adducin genes are involved in blood pressure variation.

The Milan hypertensive strain of rats (MHS) develops a genetic form of renal hypertension that, when compared to its normotensive control (MNS), shows renal dysfunction similar to that of a subset of human patients with primary hypertension. MHS and MNS were shown to be homozygous by multilocus minisatellite analysis and monolocus microsatellite markers. We show here that one point mutation in each of two genes coding for the membrane skeleton protein adducin is associated with blood pressure in the Milan strain of rats. Adducin is a heterodimer formed by alpha and beta subunits that promotes the assembly of actin with spectrin. MHS and MNS differ, respectively, by the amino acids Y and F at position 316 of the alpha subunit. In the beta-adducin locus, MHS is always homozygous for R at position 529 while in MNS either R or Q occurs in that position. The R/Q heterozygotes showed lower blood pressure than any of the homozygotes. In vitro phosphorylation studies suggest that both of these amino acid substitutions occur within protein kinase recognition sites. Analysis of an F2 generation demonstrated that Y alleles segregated with a significant increment in blood pressure. This effect is modulated by the presence of the R allele of the beta subunit. Taken together, these findings strongly support a role for adducin polymorphisms in causing variation of blood pressure in the Milan strain of rats.

Amino Acid Sequence↗
PubMed2003

Alpha-adducin dissociates from F-actin and spectrin during platelet activation.

Aspectrin-based skeleton uniformly underlies and supports the plasma membrane of the resting platelet, but remodels and centralizes in the activated platelet. alpha-Adducin, a phosphoprotein that forms a ternary complex with F-actin and spectrin, is dephosphorylated and mostly bound to spectrin in the membrane skeleton of the resting platelet at sites where actin filaments attach to the ends of spectrin molecules. Platelets activated through protease-activated receptor 1, FcgammaRIIA, or by treatment with PMA phosphorylate adducin at Ser726. Phosphoadducin releases from the membrane skeleton concomitant with its dissociation from spectrin and actin. Inhibition of PKC blunts adducin phosphorylation and release from spectrin and actin, preventing the centralization of spectrin that normally follows cell activation. We conclude that adducin targets actin filament ends to spectrin to complete the assembly of the resting membrane skeleton. Dissociation of phosphoadducin releases spectrin from actin, facilitating centralization of spectrin, and leads to the exposure of barbed actin filament ends that may then participate in converting the resting platelet's disc shape into its active form.

Actins↗
PubMed1992

Cloning and mapping of the alpha-adducin gene close to D4S95 and assessment of its relationship to Huntington disease.

The genetic defect underlying Huntington's disease (HD) has been mapped to 4p16.3. Refined localization using recombinant HD chromosome analysis and allelic association analyses have identified two distinct candidate regions. Using a cDNA hybrid selection procedure we have cloned the gene for alpha-adducin, a subunit of a cytoskeletal protein crucial for spectrin-actin membrane plasticity. This gene maps to the proximal 2.2 Mb candidate region within 20 kb of D4S95. Alleles of markers at this locus have been shown to exhibit significant linkage disequilibrium with HD. A 4 kb alpha-adducin transcript was identified which is abundantly expressed in the caudate nucleus, the site of major neuronal loss in HD. Sequencing of the brain alpha-adducin cDNA from two HD patients and an age-matched control did not detect any sequence alterations specific to HD. However, we identified in brain cDNA of both patients and control samples, two alternately spliced brain exons, not previously described in the erythrocyte cDNA. A 93 bp exon is inserted in frame between codon 471 and 472 while a 34 bp exon inserted within codon 621 disrupts the frame and introduces a stop codon after 11 novel amino acids. The mapping of the adducin gene adjacent to D4S95 and its pattern of expression, as well as its potential for distinct alternately spliced variants, reinforces the necessity to accurately assess the role of the expression of this gene in the pathogenesis of HD.

Amino Acid Sequence↗
PubMed2006

Brain-specific promoter and polyadenylation sites of the beta-adducin pre-mRNA generate an unusually long 3'-UTR.

Adducins are a family of membrane skeleton proteins composed of alpha-, beta- and gamma-subunits that promote actin and spectrin association in erythrocytes. The alpha- and gamma-subunits are expressed ubiquitously, while the beta-subunit is found in brain and erythropoietic tissues. The brain beta-adducin protein is similar in size to that of spleen, but the mRNA transcript is a brain-specific one that has not been yet characterized, having an estimated length of 8-9 kb instead of the 3-4 kb of spleen mRNA. Here, we show the molecular basis for these differences by determining the structure of the brain-specific beta-adducin transcript in rats, mice and humans. We identified a brain-specific promoter in rodents that, apparently, was not conserved in humans. In addition, we present evidence that the brain-mRNAs are formed by a common mechanism consisting in the tissue-specific use of alternative polyadenylation sites generating unusually long 3'-untranslated region of up to 6.6 kb. This hypothesis is supported by the presence of highly-conserved regions flanking the brain-specific polyadenylation site that suggest the involvement of these sequences in the translational regulation, stability and/or subcellular localization of the beta-adducin transcript in the brain.

3' Untranslated Regions↗
PubMed2004

Role of alpha-adducin DNA polymorphisms in the genetic predisposition to diabetic nephropathy.

BACKGROUND: There is substantial evidence for genetic susceptibility to diabetic nephropathy. In particular, genes that predispose to hypertension in the general population may confer susceptibility to nephropathy in patients with diabetes. A Gly460Trp variant in the alpha-adducin gene has been associated with essential hypertension. Our aim was to screen the alpha-adducin gene for polymorphisms and to determine if any variants predisposed patients with diabetes to nephropathy. A secondary objective was to assess for association between the Gly460Trp variant and hypertension. METHODS: The exons of the alpha-adducin gene were resequenced in 30 individuals. Selected variants were then genotyped in 155 patients with type 1 diabetes and nephropathy (cases) and 216 persons with type 1 diabetes but no evidence of nephropathy (controls) from Northern Ireland and in 95 cases and 118 controls from the Irish Republic. RESULTS: Eleven polymorphisms were detected, of which six were novel and three caused amino-acid substitutions. The Gly460Trp and a novel Ser617Cys polymorphism were in strong linkage disequilibrium (D' = 0.98). Neither the genotype nor allele frequencies for the Gly460Trp polymorphism (P = 0.89 and 0.93 respectively) or the Ser617Cys polymorphism (P = 0.46 and 0.76) were significantly different between cases and controls when the Northern Ireland and Irish Republic sample groups were combined. Carriage of the 460Trp allele was not significantly associated with systolic or diastolic blood pressure in either the cases (P = 0.48 and 0.06, respectively) or in the controls (P = 0.50 and 0.94, respectively). CONCLUSIONS: Variation in the alpha-adducin gene does not play a major role in the development of nephropathy in persons with type 1 diabetes in the Irish population. Furthermore, the Gly460Trp variant was not associated with hypertension in this population.

Adult↗
PubMed1988

Characterization of erythrocyte adducin from the Milan hypertensive strain of rats.

Previous studies showed that erythrocytes from the Milan hypertensive strain of rats (MHS) are smaller and have a faster Na-K cotransport when compared with their normotensive controls (MNS). These characteristics are determined within the stem cell, are genetically associated with hypertension and are similar to other renal tubular cell abnormalities more directly involved in the development of hypertension in MHS. The difference in volume is maintained in ghost membranes, while the difference in transport is abolished in inside-out vesicles. Ghosts and cytoskeletons contain a 105-kilodalton protein already characterized by immunoblotting. This protein has been identified with erythrocyte adducin by several criteria, including binding to calmodulin and protein kinase C, phosphorylation and full immunological cross-reactivity with human adducin. Since only MHS rats immunized with MNS erythrocyte cytoskeletons produce anti-adducin antibodies, we suggest an immunogenic structural difference in adducin from the two strains, and an involvement of this difference in the alteration of Na-K cotransport observed.

Animals↗
PubMed2002

alpha-Adducin Gly460Trp polymorphism, left ventricular mass and plasma renin activity.

OBJECTIVE: Left ventricular hypertrophy (LVH) is associated with an increased risk for cardiovascular morbidity and mortality. Epidemiological studies suggest that LVH may be influenced by genetic factors. However, the evidence associating individual genes with left ventricular (LV) mass is inconsistent and contradictory. METHODS: We investigated the association between angiotensin-converting enzyme insertion/deletion, angiotensinogen and alpha-adducin polymorphisms with LV mass and plasma renin activity (PRA) in 162 men with mild, never-treated hypertension who were recruited for the Hypertension and Ambulatory Recording Venetia Study. The effect of each polymorphism on LV mass and PRA was tested in one-way analysis of covariance using LV mass index or PRA as the dependent variable after adjusting for covariates. RESULTS: The alpha-adducin polymorphism was the only individual polymorphism independently associated with LV mass index (F = 7.78, P= 0.006). Patients homozygous for the allele of that polymorphism had a LV mass index (123.4 +/- 10.5 g/m(2) ) significantly higher compared with heterozygotes (90.8 +/- 2.5 g/m(2) , P<0.01) or homozygotes (94.7 +/- 1.7 g/m(2) , P<0.05). These subjects also have significantly lower PRA (F = 4.2, P= 0.017). Albeit uncommon, 40% of homozygotes of the alpha-adducin polymorphism had LVH (odds ratio, 15.1; 95% confidence interval, 3.0-82.1). CONCLUSIONS: The homozygotic state of the allele of alpha-adducin polymorphism is independently associated with increased LV mass and low PRA. These data suggest that genetic considerations may contribute importantly to risk stratification, and perhaps therapeutic interventions targeted at LVH and the renin-angiotensin system in hypertensive patients.

Adult↗
PubMed2003

Blood pressure phenotypes in relation to the beta-adducin C1797T polymorphism in the European Project on Genes in Hypertension (EPOGH).

METHODS: The association of blood pressure (BP) with the beta-adducin C1797 T polymorphism was investigated in 388 men and 456 women aged 18-60 years recruited from three European populations (Cracow, Poland, n=300; Novosibirsk, Russian Federation, n=274; Mirano, Italy; n=270). Phenotypes included conventional measurements of BP obtained at the second contact with the subjects and 24-h ambulatory BP. Subjects were genotyped for the beta-adducin C1797 T polymorphism. Both a population-based association study and a family-based analysis were performed. RESULTS: Urinary sodium excretion was higher in Cracow than in Mirano (241 versus 185 mmol/day, P<0.05) and intermediate in Novosibirsk (206 mmol/day). The beta-adducin T allele (15.2 versus 9.1%, P<0.0001) was more prevalent in Mirano than in the two Slavic centres. In both population-based and family-based association analyses, there was significant heterogeneity between Slavic and Italian subjects in the phenotype-genotype relationships with beta-adducin. Adjusted population-based analyses demonstrated that in the two Slavic centres, values of systolic pressure obtained by 24-h, daytime and night-time ambulatory monitoring, but not those measured by conventional sphygmomanometry at home, were significantly higher in T allele carriers than in CC homozygotes. These results were confirmed in the family-based analysis of offspring using a quantitative transmission disequilibrium test. CONCLUSIONS: Phenotype-genotype associations involving blood pressure are influenced by the technique and conditions of the BP measurement as well as by the overall ecogenetic context.

Adolescent↗
PubMed2006

Screening for the alpha-adducin Gly460Trp variant in hypertensive patients: a cost-effectiveness analysis.

BACKGROUND: Studies have shown that approximately 80% of hypertensive patients do not take diuretics despite their recommendation as a first-line therapy. A recent study reported that hypertensive patients with the Gly460Trp variant in the alpha-adducin gene are more likely to benefit from diuretic therapy. The objective of this study was to evaluate the potential cost effectiveness of screening for the alpha-adducin Gly460Trp variant among hypertensive patients. METHODS: A decision analytic Markov model was developed to estimate the clinical and economic outcomes comparing screening for the Gly460Trp variant to identify patients for addition of a diuretic compared to no screening and no addition of diuretic (usual care) in a hypothetical cohort of treated hypertensive patients not receiving diuretic therapy. We used a lifetime horizon and payer perspective. Cost, utility and epidemiological data were obtained from the literature. One-way, probabilistic, and scenario sensitivity analyses were conducted to evaluate the uncertainty in the results. RESULTS: The screening strategy increased quality adjusted life years (QALYs) by 0.14 (95% confidence range [CR]: 0.05, 0.36) and saved dollar 1834 (dollar 505, dollar 5174) compared to usual care. The most influential input was the strength of the interaction between the alpha-adducin gene variant and diuretic effect. CONCLUSIONS: Our results suggest that screening for the alpha-adducin gene variant may be a useful mechanism to identify patients most likely to benefit from diuretic therapy and improve compliance with current treatment guidelines.

Aged↗
PubMed2003

Genetics of hypertension: the adducin paradigm.

The following were investigated: (1) how we became interested in studying adducin genes and what we know about adducin; (2) studies in animals and humans supporting the role of adducin polymorphisms in hypertension, including some methodological problems related to the dissection of the role of a given genetic molecular mechanism in a complex multifactorial polygenic disease like hypertension; (3) biochemical mechanisms underlying the effect of adducin and its interaction with the Na-K pump; and (4) future directions.

Animals↗
PubMed2006

Rostafuroxin: an ouabain antagonist that corrects renal and vascular Na+-K+- ATPase alterations in ouabain and adducin-dependent hypertension.

The genetic and environmental heterogeneity of essential hypertension is responsible for the individual variability of antihypertensive therapy. An understanding of the molecular mechanisms underlying hypertension and related organ complications is a key aspect for developing new, effective, and safe antihypertensive agents able to cure the cause of the disease. Two mechanisms, among others, are involved in determining the abnormalities of tubular Na+ reabsorption observed in essential hypertension: the polymorphism of the cytoskeletal protein alpha-adducin and the increased circulating levels of endogenous ouabain (EO). Both lead to increased activity and expression of the renal Na+-K+ pump, the driving force for tubular Na transport. Morphological and functional vascular alterations have also been associated with EO. Rostafuroxin (PST 2238) is a new oral antihypertensive agent able to selectively antagonize EO, adducin pressor, and molecular effects. It is endowed with high potency and efficacy in reducing blood pressure and preventing organ hypertrophy in animal models representative of both adducin and EO mechanisms. At molecular level, in the kidney, Rostafuroxin antagonizes EO triggering of the Src-epidermal growth factor receptor (EGFr)-dependent signaling pathway leading to renal Na+-K+ pump, and ERK tyrosine phosphorylation and activation. In the vasculature, it normalizes the increased myogenic tone caused by nanomolar ouabain. A very high safety ratio and an absence of interaction with other mechanisms involved in blood pressure regulation, together with initial evidence of high tolerability and efficacy in hypertensive patients, indicate Rostafuroxin as the first example of a new class of antihypertensive agents designed to antagonize adducin and EO-hypertensive mechanisms.

Androstanols↗
PubMed2003

Influence of the alpha-adducin and ACE gene polymorphism on the progression of autosomal-dominant polycystic kidney disease.

BACKGROUND: A significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD). The variability can not be fully explained by the genetic heterogeneity of the disease. We examined the influence of the ACE I/D polymorphism, adducin Trp460Gly polymorphism and the association of both polymorphisms on the progression of ADPKD towards end-stage renal failure (ESRF). METHODS: 320 ADPKD patients (pts) were analyzed, 220 pts (113 males, 107 females) with ESRF before 63 years of age, with a subgroup (rapid progressors) of 20 pts (12 males, 8 females) with ESRF before 40 years of age, 52 pts (23 males, 29 females) with ESRF later than 63 years of age (slow progressors), 48 ADPKD pts (18 males, 30 females) with mean age +/-50 years with serum creatinine <110 micromol/l (slow progressors) and 200 genetically unrelated healthy Czech subjects. DNA samples from collected blood were genotyped for the ACE I/D polymorphism and the Trp460Gly of alpha-adducin gene polymorphism. RESULTS: The alpha-adducin genotypes showed no differences among the groups of slow progressors (74% Gly/Gly, 22.9% Gly/Trp and 3.1% Trp/Trp), pts with ESRF before 63 years of age (67.7% Gly/Gly, 30.5% Gly/Trp and 1.8% Trp/Trp) and rapid progressors (75% Gly/Gly, 25% Gly/Trp). The ACE genotypes did not differ among the groups of slow progressors (27.1% I/I, 44.8% I/D and 28.1% D/D), pts with ESRF before 63 years of age (23.6% I/I, 51.4% I/D and 25% D/D) and rapid progressors (20% I/I, 55% I/D and 25% D/D). The distribution did not differ from the control group. The ages of ESRF according to different genotypes did not significantly differ. We observed a significant tendency to better prognosis in Trp allele carriers for I/I genotype in comparison with Gly/Gly homozygous subjects. CONCLUSION: The ACE and alpha-adducin polymorphisms do not play a significant role in the progression of ADPKD to ESRF.

Adult↗
PubMed2005

Adducin polymorphism: detection and impact on hypertension and related disorders.

Adducin is a heterodymeric cytoskeleton protein, the 3 subunits of which are encoded by genes (ADD1, ADD2, ADD3) mapping to 3 different chromosomes. A long series of parallel studies in the Milan hypertensive rat strain model of hypertension and humans indicated that an altered adducin function may cause hypertension through an enhanced constitutive tubular sodium reabsorption. Six human linkage studies showed positive results when a DNA marker mapping to 30 kb from the ADD1 locus or single-nucleotide polymorphisms (SNPs) of 1 of the 3 adducin genes were considered either alone or in combination with each other or angiotensin-converting enzyme (ACE) D allele or salt intake. When DNA markers mapping at much larger distance from the ADD1 locus were used, negative results were found by 4 studies. Positive results were also obtained in 18 of 20 association studies that, in addition to blood pressure, investigated variables reflecting body sodium or the renin-angiotensin system. Mixed results regarded case-control studies or studies in predominantly normotensive populations that did not consider the above-mentioned variables. Four of 5 studies showed a selective beneficial effect of diuretics in carriers of the mutated ADD1. Twelve of 16 studies found that ADD1 polymorphism alone or in combination with that of ACE positively associates with stroke or coronary heart disease or renal or vascular dysfunctions. In conclusion, when context is taken into account, the impact of adducin in hypertension and its related disorders is clear.

Animals↗
PubMed2005

Cardiovascular risk in relation to alpha-adducin Gly460Trp polymorphism and systolic pressure: a prospective population study.

Preliminary evidence from 1 case-control study suggested that in hypertensive patients, the alpha-adducin 460Trp allele might be associated with a 2-fold higher risk of coronary heart disease. In a prospective population study, we investigated whether the alpha-adducin Gly460Trp polymorphism predicted mortality and morbidity. From August 1985 until July 2003, we randomly recruited 2235 Belgian residents. We obtained information on vital status (until July 1, 2004) and the incidence of events via registries and repeat examinations (median 3). In Cox regression, before and after adjustment for other risk factors, we found strong interaction between systolic blood pressure at baseline, analyzed as a continuous variable, and the alpha-adducin polymorphism in relation to total (P=0.01) and cardiovascular mortality (P=0.007) and all cardiovascular (P=0.003), cardiac (P=0.001), and coronary events (P=0.03). The hazard ratio for total mortality associated with the Trp allele relative to GlyGly homozygosity was 2.30 (95% confidence interval, 1.12 to 4.72; P=0.02) in patients with stage-2 systolic hypertension (> or =160 mm Hg) and 0.88 (0.61 to 1.26; P=0.48) in the other participants. For all cardiovascular complications, these estimates were 2.94 (1.28 to 6.74; P=0.01) and 0.83 (0.58 to 1.20; P=0.32), respectively. For all cardiovascular events, the positive predictive value and the attributable risk associated with the Trp allele in patients with stage-2 systolic hypertension were 76.9% and 44.3%, respectively. In conclusion, the alpha-adducin Gly460Trp polymorphism, in combination with systolic blood pressure, is a strong predictor of cardiovascular mortality and morbidity.

Adolescent↗
PubMed1998

Human alpha-adducin gene, blood pressure, and sodium metabolism.

The adducin genes contribute significantly to population variation in rat blood pressure and cell membrane sodium transport. The 460Trp mutation of the human alpha-adducin gene has been associated with hypertension, in particular hypertension sensitive to sodium restriction. We studied the relationship between the 460Trp mutation and population variation in blood pressure and sodium metabolism. From 603 Scottish families, we selected 151 offspring and 224 parents with blood pressures in either the upper (high) or bottom (low) 30% of the population distribution and measured the 460Trp mutation using allele-specific hybridization. In offspring, we also measured exchangeable sodium, plasma volume, and total body water. Plasma levels of components of the renin-angiotensin system, atrial natriuretic peptide, and cellular sodium and transmembrane sodium efflux were also estimated. The overall frequency of the 460Trp mutation was 27.1%. In offspring and parent groups, we found no difference in the genotype or allele frequencies of the 460Trp mutation between subjects with high or low blood pressure. There was no overall association between the alpha-adducin genotypes and blood pressure variation. In offspring, the 460Trp mutation was not associated with any significant differences in body fluid volumes or exchangeable sodium; levels of plasma renin, angiotensin II, aldosterone, or atrial natriuretic peptide; intracellular sodium; or ouabain-sensitive transmembrane sodium efflux. These findings suggest that in our Scottish population, the alpha-adducin 460Trp polymorphism is not related to blood pressure and does not affect whole body or cellular sodium metabolism.

Adolescent↗