Modulation of adipocytokines response and weight loss secondary to a hypocaloric diet in obese patients by -55CT polymorphism of UCP3 gene.

Decreased expression or function of UCP3 (uncoupling protein 3) could reduce energy expenditure and increase the storage of energy as fat. Some studies have pointed to a role of UCP3 in the regulation of whole body energy homeostasis, diet induced obesity, and regulation of lipids as metabolic substrates. The C/C genotype of a polymorphism in the UCP3 promoter (-55C-->T) is associated with an increased expression of UCP3 mRNA in muscle. The aim of our study was to investigate the influence of -55CT polymorphism of UCP3 gene on adipocytokines response and weight loss secondary to a hypocaloric diet in obese patients. A population of 107 obese (body mass index >30) nondiabetic outpatients was analyzed in a prospective way. Before and after three months of a hypocaloric diet, an indirect calorimetry, tetrapolar electrical bioimpedance, blood pressure, a serial assessment of nutritional intake with 3-day written food records, and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1520 kcal, 52% of carbohydrates, 25% of lipids and 23% of proteins). The exercise program consisted of aerobic exercise for at least 3 times per week (60 minutes each). The mean age was 49.5+/-34.5 years and the mean BMI 34.5+/-4.8, with 27 males (25.3%) and 80 females (74.7%). Ninety patients (25 males/65 females) (83.6%) had the genotype 55CC (wild group) and 17 patients (2 male/15 females) (16.4%) 55CT (mutant group). The percentage of responders (weight loss) was similar in both groups (wild group: 84.7% vs. mutant group: 81.8%). BMI, weight, fat mass, systolic blood pressure, LDL cholesterol, waist circumference, and waist-to-hip ratio decreased in the wild group and RMR and VO (2) were increased. In the mutant group, BMI and weight decreased. Leptin and IL-6 levels have a significant decrease in the wild group (9.6%: p<0.05) and (30.5%: p<0.05), respectively. Patients with -55CC genotype have a significant decrease in leptin, interleukin 6, BMI, weight, fat mass, systolic blood pressure, LDL cholesterol, waist circumference, waist-to-hip ratio weight, fat mass, and systolic blood pressure.     

Unchanged iron and copper and increased zinc in the blood of obese children after two hypocaloric diets

Serum iron (sFe), and ferritin (sFert), transferrin saturation index (TSI), plasma zinc and copper (pZn, pCu), and erythrocyte zinc content (eZn) were measured in 55 obese children and adolescents (28 males and 27 females) before and after a 13-wk treatment with a hypocaloric balanced diet (HCBD, 22 subjects) or a 10-wk treatment with a protein sparing modified fast diet (PSMF, 33 subjects). The energy intake provided by the HCBD and PSMF diet was calculated to be 60 and 25%, respectively, of the recommended dietary allowances (RDAs) for age and sex. Neither diet was supplemented with trace elements or calcium. Using a visual memory system, all subjects had a 24-h dietary intake recall before starting the weight-loss program. Iron, zinc, and copper intakes from the 24-h recall were compared with those from prescribed diets. Both diets produced a significant (p<0.001) weight reduction with a significant reduction in the arm muscle area of the PSMF group. After treatment, no significant change was observed in sFe, sFert, and TSI of either group, whereas eZn increased significantly in the HCBD and the PSMF groups (p=0.001 andp<0.006, respectively), with an improvement of the erythrocyte index (E.I.). A significant increase in pZn was also observed in the PSMF group (p=0.007). When compared with the usual intakes, HCBD supplied less iron (p=0.04) and more copper (p=0.001), whereas PSMF provided more zinc (p=0.026).     

Role of G1359A polymorphism of the cannabinoid receptor gene on weight loss and adipocytokines levels after two different hypocaloric diets

BackgroundA silent intragenic polymorphism (1359 G/A) of the cannabinoid receptor 1 gene resulting in the substitution of the G to A at nucleotide position 1359 in codon 435 (Thr) was reported as a common polymorphism in Caucasian populations. Intervention studies with this polymorphism have not been realized.ObjectiveWe decide to investigate the role of missense polymorphism (G1359A) of cannabinoid receptor 1 gene on adipocytokines response and weight loss secondary to a low-fat versus a low-carbohydrate diet in obese patients.DesignA population of 249 patients was analyzed. A nutritional evaluation was performed at the beginning and at the end of a 3-month period in which subjects received one of two diets (diet I: low fat vs. diet II: low carbohydrate).ResultsOne hundred forty three patients (57.4%) had the genotype G1359G (wild-type group), and 106 (42.6%) patients had G1359A (92 patients, or 36.9%) or A1359A (14 patients, or 5.6%; mutant-type group). With both diets in wild-type and mutant-type groups, body mass index (BMI), weight, fat mass, waist circumference and systolic blood pressure levels decreased. With both diets and in wild-type group, glucose, total cholesterol and insulin levels and homeostasis model assessment test score decreased. No metabolic effects were observed in mutant-type group. Leptin levels decreased significantly in the wild-type group with both diets (diet I: 10.8% vs. diet II: 28.9%; P<.05).ConclusionThe novel finding of this study is the lack of metabolic improvement of the mutant-type groups G1359A and A1359A after weight loss with both diets. Decrease in leptin level was higher with low-carbohydrate diet than low-fat diet.     

Genetic variation in the cannabinoid receptor gene (CNR1) (G1359A polymorphism) and their influence on anthropometric parameters and metabolic parameters under a high monounsaturated vs. high polyunsaturated fat hypocaloric diets

An intragenic polymorphism (1359 G/A) of the cannabinoid receptor 1 (CNR1) gene was reported as a common polymorphism in Caucasian populations (rs1049353). Intervention studies with this polymorphism have yield contradictories results. We decide to investigate the role of polymorphism (G1359A) of (CNR1) gene on metabolic parameters and weight loss secondary to a high monounsaturated fat and high polyunsaturated fat hypocaloric diets in obese subjects. A population of 258 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 3-month period in which subjects received 1 of 2 diets (diet M: high monounsaturated fat diet vs diet P: high polyunsaturated fat diet). One hundred and sixty five patients (63.9%) had the genotype G1359G and 93 (36.1%) patients (A allele carriers) had G1359A (78 patients,30.3%) or A1359A (15 patients,5.8%) genotypes. In subjects with both genotypes, body mass index, weight, fat mass, waist circumference and systolic blood pressures decreased with both diets. With the diet-type M and in both genotype groups, biochemical parameters remained unchanged. After the diet type P and in subjects with both genotypes, glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, insulin and homeostasis model assessment for insulin resistance (HOMA-IR) levels decreased. In G1359G genotype subjects after both diets, leptin levels decreased. The finding of this study is the association of the A allele with a lack of improvement on leptin levels. Subjects with both genotypes and after a high polyunsaturated fat hypocaloric diet showed a significant improvement of LDL cholesterol, total cholesterol, HOMA-IR and insulin levels.     

肥胖犬白细胞中相关基因及血浆生化指标的变化

目的观察不同肥胖时期的犬血浆中相关生化指标和外周血液白细胞(peripheral blood leukocytes,PBL)中胰岛素和脂联素通路、能量和脂类代谢相关基因的变化,为开发肥胖犬代谢紊乱的早期诊断法提供依据。方法选用到动物医院进行常规体检的不同品种的犬59只,按照5分制的身体评分指数分为正常犬(26只)、超重犬(28只)和肥胖症犬(5只),分别检测血浆中生化代谢指标(葡萄糖、血尿素氮、肌氨酸酐、总胆固醇、总蛋白质、三酸甘油酯、乳酸脱氢酶、碱性磷酸酶、天冬氨酸转氨酶、丙氨酸转氨酶、非酯化脂肪酸、脂联素和免疫反应胰岛素)和PBL中相关基因[胰岛素受体底物(IRS-1,-2)、磷脂酰肌醇-3-激酶(PI3-K p85α),苹果酸脱氢酶(malate de-hydrogenase,MDH)、葡萄糖-6-磷酸脱氢酶(G6DPH)、脂肪酸合酶(FAS)、脂联素受体(ADIPOR1,2)]mRNA表达量。结果与对照犬相比,超重犬和肥胖犬血浆中的胰岛素含量显著升高,肥胖犬非酯化脂肪酸、总胆固醇和三酸甘油酯显著升高。肥胖犬PBL中胰岛素下游相关基因IRS-2、脂类代谢基因FAS和能量代谢基因MDH的mRNA表达量显著下降。结论肥胖犬患有高胰岛素血症和严重的脂类代谢紊乱,胰岛素下游基因和其他代谢相关基因的显著下降可能提示肥胖犬患有胰岛素抵抗和能量代谢紊乱。     

Modulation of 14-3-3 protein interactions with target polypeptides by physical and metabolic effectors

The proteins commonly referred to as 14-3-3s have recently come to prominence in the study of protein:protein interactions, having been shown to act as allosteric or steric regulators and possibly scaffolds. The binding of 14-3-3 proteins to the regulatory phosphorylation site of nitrate reductase (NR) was studied in real-time by surface plasmon resonance, using primarily an immobilized synthetic phosphopeptide based on spinach NR-Ser543. Both plant and yeast 14-3-3 proteins were shown to bind the immobilized peptide ligand in a Mg2+-stimulated manner. Stimulation resulted from a reduction in KD and an increase in steady-state binding level (Req). As shown previously for plant 14-3-3s, fluorescent probes also indicated that yeast BMH2 interacted directly with cations, which bind and affect surface hydrophobicity. Binding of 14-3-3s to the phosphopeptide ligand occurred in the absence of divalent cations when the pH was reduced below neutral, and the basis for enhanced binding was a reduction in K(D). At pH 7.5 (+Mg2+), AMP inhibited binding of plant 14-3-3s to the NR based peptide ligand. The binding of AMP to 14-3-3s was directly demonstrated by equilibrium dialysis (plant), and from the observation that recombinant plant 14-3-3s have a low, but detectable, AMP phosphatase activity.     

Hypoxia-induced decrease of UCP3 gene expression in rat heart parallels metabolic gene switching but fails to affect mitochondrial respiratory coupling

Mitochondrial uncoupling proteins 2 and 3 (UCP2 and UCP3) are postulated to contribute to antioxidant defense, nutrient partitioning, and energy efficiency in the heart. To distinguish isotype function in response to metabolic stress we measured cardiac mitochondrial function and cardiac UCP gene expression following chronic hypobaric hypoxia. Isolated mitochondrial O(2) consumption and ATP synthesis rate were reduced but respiratory coupling was unchanged compared to normoxic groups. Concurrently, left ventricular UCP3 mRNA levels were significantly decreased with hypoxia (p<0.05) while UCP2 levels remained unchanged versus controls. Diminished UCP3 expression was associated with coordinate regulation of counter-regulatory metabolic genes. From these data, we propose a role for UCP3 in the regulation of fatty acid oxidation in the heart as opposed to uncoupling of mitochondria. Moreover, the divergent hypoxia-induced regulation of UCP2 and UCP3 supports distinct mitochondrial regulatory functions of these inner mitochondrial membrane proteins in the heart in response to metabolic stress.     

Improvement of metabolic parameters and vascular function by metformin in obese non-diabetic rats

AimsMetformin is an insulin sensitizing agent with beneficial effects in diabetic patients on glycemic levels and in the cardiovascular system. We examined whether the metabolic changes and the vascular dysfunction in monosodium glutamate-induced obese non-diabetic (MSG) rats might be improved by metformin.Main methods16 week-old MSG rats were treated with metformin for 15 days and compared with age-matched untreated MSG and non-obese non-diabetic rats (control). Blood pressure, insulin sensitivity, vascular reactivity and prostanoid release in the perfused mesenteric arteriolar bed as well as nitric oxide production and reactive oxygen species generation in isolated mesenteric arteries were analyzed.Key findings18-week-old MSG rats displayed higher Lee index, fat accumulation, dyslipidemia, insulin resistance and hyperinsulinemia. Metformin treatment improved these alterations. The norepinephrine-induced response, increased in the mesenteric arteriolar bed from MSG rats, was corrected by metformin. Indomethacin corrected the enhanced contractile response in MSG rats but did not affect metformin effects. The sensitivity to acetylcholine, reduced in MSG rats, was also corrected by metformin. Indomethacin corrected the reduced sensitivity to acetylcholine in MSG rats but did not affect metformin effects. The sensitivity to sodium nitroprusside was increased in preparations from metformin-treated rats. Metformin treatment restored both the reduced PGI2/TXA2 ratio and the increased reactive oxygen species generation in preparations from MSG rats.SignificanceMetformin improved the vascular function in MSG rats through reduction in reactive oxygen species generation, modulation of membrane hyperpolarization, correction of the unbalanced prostanoids release and increase in the sensitivity of the smooth muscle to nitric oxide.     

Beneficial effect of CLOCK gene polymorphism rs1801260 in combination with low-fat diet on insulin metabolism in the patients with metabolic syndrome

Genetic variation at the Circadian Locomotor Output Cycles Kaput (CLOCK) locus has been associated with lifestyle-related conditions such as obesity, metabolic syndrome (MetS) and cardiovascular diseases. In fact, it has been suggested that the disruption of the circadian system may play a causal role in manifestations of MetS. The aim of this research was to find out whether habitual consumption of a low-fat diet, compared with a Mediterranean diet enriched with olive oil, modulates the associations between common CLOCK single nucleotide polymorphisms (SNPs) (rs1801260, rs3749474 and rs4580704) and lipid and glucose-related traits among MetS patients. Plasma lipid and insulin concentrations, indexes related with insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI)) and CLOCK SNPs were determined in 475 MetS subjects participating in the CORDIOPREV clinical trial (NCT00924937). Gene–diet interactions were analyzed after a year of dietary intervention (Mediterranean diet (35% fat, 22% monounsaturated fatty acids (MUFA)) versus low-fat diet (28% fat, 12% MUFA)). We found significant gene–diet interactions between rs1801260 SNP and the dietary pattern for insulin concentrations (p?=?0.009), HOMA-IR (p?=?0.014) and QUICKI (p?=?0.028). Specifically, after 12 months of low-fat intervention, subjects who were homozygous for the major allele (TT) displayed lower plasma insulin concentrations (p?=?0.032), lower insulin resistance (HOMA-IR; p?=?0.027) and higher insulin sensitivity (QUICKI; p?=?0.024) compared with carriers of the minor allele C (TC?+?CC). In contrast, in the Mediterranean intervention group a different trend was observed although no significant differences were found between CLOCK genotypes after 12 months of treatment. Our data support the notion that a chronic consumption of a healthy diet may play a contributing role in triggering glucose metabolism by interacting with the rs1801260 SNP at CLOCK gene locus in MetS patients. Due to the complex nature of gene–environment interactions, dietary adjustment in subjects with the MetS may require a personalized approach.     

The common -866G/A polymorphism of the UCP2 gene in healthy Iranians compared with world populations

Uncoupling protein 2 (UCP2) is a member of the mitochondrial transporter superfamily. It is proposed as a candidate gene for obesity. A common G/A polymorphism in the promoter region of this gene is associated with enhanced adipose tissue mRNA expression in vivo. Using a PCR-RFLP method, we genotyped the UCP2 -866G/A polymorphism in 75 unrelated nonobese nondiabetic Iranians. The frequencies of the UCP2 -866G/A genotypes in 75 Iranian normal subjects were 7 (9.4%) for AA, 41 (54.6%) for GA, and 27 (36%) for GG. Significantly higher HDL cholesterol was detected in people with the GG genotype (p = 0.02) compared to individuals with the GA and AA genotypes. The frequency distribution results were compared with data from Japanese, Italians, Germans, Austrians, and Danes. Our allele frequencies were significantly different from the Japanese data from two different reports (P < 0.025) but not from the others. The Japanese data showed a higher frequency of the AA genotype, which is associated with a low prevalence of obesity, than the Caucasian individuals' data did. In conclusion, a single nucleotide polymorphism in the promoter region of the UCP2 gene has a significant association with HDL cholesterol level in Iranian nonobese nondiabetic subjects. Also, our allele-frequency distribution for this single nucleotide polymorphism is closer to European Caucasians than to Japanese in nonobese nondiabetic individuals.     

Role of insulin and counter-regulatory hormones in the metabolic changes caused by insulin deprivation in diabetic patients

In eight insulin dependent diabetic patients treated by continuous subcutaneous insulin infusion (1.1 +/- 0.2 U/h), the levels (measured hourly from 23 h to 05 h) of blood glucose, non esterified fatty acids (NEFA), glycerol and 3-OH-butyrate (3-OH-B) have been correlated to the circulating levels of free insulin (FIRI), glucagon, growth hormone or cortisol, in two experimental conditions: A. Insulin being infused as usual (physiological FIRI levels) and B. Progressively declining FIRI levels (insulin infusion arrested at 23 h). In condition A, blood glucose levels correlated significantly to both insulin and glucagon; NEFA, glycerol and 3OH-B correlated only to insulin. In condition B, blood glucose was significantly correlated to insulin but not to glucagon while NEFA, glycerol and 3-OH-B were significantly correlated to both hormones but not to growth hormone or cortisol. Therefore, on the metabolic deterioration that follows insulin withdrawal, growth hormone and cortisol seem to play a minor role, the main role being played by the decrease in circulating insulin levels and to a lesser extent by the increase in glucagon levels.     

Association of the -514C-->T polymorphism in the hepatic lipase gene (LIPC) promoter with elevated fasting insulin concentrations, but not insulin resistance, in non-diabetic Germans.

Hepatic lipase hydrolyses triglycerides and phospholipids in all major classes of lipoproteins. The -514C-->T genetic variation in the hepatic lipase gene promoter was found to be associated with diminished lipase activity, dyslipidemia, and atherosclerosis. We investigated whether this polymorphism associates with hyperinsulinemia and insulin resistance in 535 normal glucose-tolerant Germans. Only in homozygous individuals (22 subjects), the T allele (frequency: 18.1 %) was significantly associated with elevated glucose concentrations after 120 min of oral glucose tolerance test (p = 0.05) and with elevated fasting concentrations of insulin (p = 0.03), triglycerides (p < 0.01), total and HDL-cholesterol (p = 0.02), as determined by multivariate linear regression analysis. In a recessive model (C/C+C/T vs. T/T), T/T was associated with decreased insulin sensitivity index (p = 0.03) as calculated from oral glucose tolerance test data (n = 535), but not with the glucose infusion rate during hyperinsulinemic euglycemic clamp (n = 218). In conclusion, we have provided evidence that, among the metabolic parameters tested, the hepatic lipase -514C-->T gene polymorphism correlates with elevated fasting insulin concentrations in a German population. Since no corresponding difference in insulin sensitivity was seen in the clamp-subgroup, an effect of this polymorphism on insulin clearance has to be considered.     

Correlation of the -3826A >G polymorphism in the promoter of the uncoupling protein 1 gene with obesity and metabolic disorders in obese families from southern Poland

The aim of the study was to examine the allelic frequency of the -3826A > G mutation of UPC1 in patients with familiar obesity and to investigate putative association of this polymorphism with metabolic disorders. One hundred and eighteen overweight /obese patients participated in the study. The UCP1 polymorphism was determined by RFLP. Glucose, lipid, insulin and leptin levels were measured both during OGTT and OLTT. The majority of patients had a homozygous A/A genotype (51,38%), while 14,68% had a G/G genotype. We found no significant association of the G allele with either BMI or glucose tolerance. Patients with the homozygous G/G genotype had significantly higher fasting levels of TG (p < 0.04) and decreased levels of HDL-cholesterol (p = 0,004). They also had an increased concentration of FFA and the rise of TG levels during the OLTT compared to controls was significant (p = 0,058). In addition, the carriers of the G/G genotype had the lowest insulin levels both during OGTT and OLTT. In our study we have demonstrated that the -3826A > G polymorphism of UCP1 does not play a major role in the development of obesity and/or disturbances of glucose metabolism. However, the increased levels of TG and FFA and decreased levels of HDL observed in carriers of the G allele suggest FFA-induced impairment of the HDL turnover and disturbance of the beta-cell function, both of which are risk factors for endothelial injury.     

Behavior of plasma insulin and GIP in obese patients subjected to biliopancreatic bypass

Biliopancreatic bypass for obesity entails a 2/3 distal gastrectomy with Roux-en-Y reconstruction, being the small bowel transected at its midpoint and the enteroenteroanastomosis placed 50 cm proximal to the ileocecal valve. Insulin and GIP fasting and meal-stimulated plasma concentrations were determined in 13 nonobese healthy volunteers, in 13 nonoperated obese patients, in 11 subjects within two months, in 12 subjects four to twelve months, and in 7 subjects fifteen to twenty months after operation. Insulin in the obese patients was significantly higher than in the control group. Postoperatively these patients showed a sharp reduction in basal and postprandial values. Plasma insulin levels, both basally and following the test meal, were very similar in the 15-20 month and the control group. Plasma GIP fasting level, meal-stimulated peak and integrated response in the obese group were higher than in control group. Due to the extreme variability among subjects in the obese group, the difference was significant only for the mean peak response. All values were greatly reduced after surgery. The mean fasting level in the 15-20 month group was very similar to that in the control group, and both peak and integrated responses were significantly lower than in the preoperative and control groups.     

Apolipoprotein E polymorphism in the Finnish population: gene frequencies and relation to lipoprotein concentrations

ApoE phenotypes were determined in 615 unrelated Finnish individuals. The apoE gene frequencies observed (epsilon 2, 0.041; epsilon 3, 0.733; epsilon 4, 0.227) differ significantly from those in other populations. The frequency of the allele epsilon 2 was lower and that of epsilon 4 higher than in all other studied populations. Plasma lipids and apolipoproteins A-I, A-II and B were recorded in 207 of the typed subjects. By comparison with the most frequent homozygous apoE 3/3 phenotype, it was found that total cholesterol, LDL-cholesterol, and apoB concentrations were all markedly higher in apoE 4/4 and to a lesser degree in apoE 4/3 phenotypic groups. On the other hand, these lipid and apolipoprotein levels tended to be lower in E-2 heterozygotes. These data confirm and extend, in a different ethnic group, previous results of an effect of apoE genes on plasma lipoprotein concentrations. The data suggest that the apoE gene locus may be one factor responsible for the high LDL cholesterol concentrations in the Finnish population.     

From hormones to secondary metabolism: the emergence of metabolic gene clusters in plants

Gene clusters for the synthesis of secondary metabolites are a common feature of microbial genomes. Well-known examples include clusters for the synthesis of antibiotics in actinomycetes, and also for the synthesis of antibiotics and toxins in filamentous fungi. Until recently it was thought that genes for plant metabolic pathways were not clustered, and this is certainly true in many cases; however, five plant secondary metabolic gene clusters have now been discovered, all of them implicated in synthesis of defence compounds. An obvious assumption might be that these eukaryotic gene clusters have arisen by horizontal gene transfer from microbes, but there is compelling evidence to indicate that this is not the case. This raises intriguing questions about how widespread such clusters are, what the significance of clustering is, why genes for some metabolic pathways are clustered and those for others are not, and how these clusters form. In answering these questions we may hope to learn more about mechanisms of genome plasticity and adaptive evolution in plants. It is noteworthy that for the five plant secondary metabolic gene clusters reported so far, the enzymes for the first committed steps all appear to have been recruited directly or indirectly from primary metabolic pathways involved in hormone synthesis. This may or may not turn out to be a common feature of plant secondary metabolic gene clusters as new clusters emerge.     

G-protein beta-3 subunit gene C825 T polymorphism: influence on plasma sodium and potassium concentrations in essential hypertensive patients

The C825T polymorphism of the beta-3 subunit of the protein G (GNB3) has been related to an increased activity of the Na+/H+ exchanger (NHE-1) through the synthesis of an anomalous hyperactive protein. Because of the important role of this system in essential hypertension (EH), we analysed the distribution of the different genotypes of this polymorphism in normotensive subjects (NS) and essential hypertensive patients (EHP), their relationship with the condition of salt sensitivity, plasma sodium and potassium concentrations and plasma renin activity (PRA) in EHP. 144 subjects (78 EHP and 76 NS) were studied. Salt sensitivity was assessed by the rapid protocol of Weinberger and genotype determination for GNB3 C825T polymorphism was performed by PCR. The distribution of the different genotypes was similar among EHP (CC 37.2%; CT 41.1%; TT 16.7%) and NS (CC 32.9%; CT 55.3%; TT 11.8%). In regard to general characteristics of EHP (including blood pressure levels) and the condition of salt sensitivity, there were no differences among the different genotypes. Plasma sodium concentration was higher and plasma potassium was lower in TT patients (141.0+/-1.7 and 3.7+/-0.1) than in CC patients (139.1+/-1.9 and 4.0+/-0.3) p<0.05. CT patients had intermediate values (139.9+/-1.9 and 3.9+/-0.2). PRA values were similar in the three genotypes as were the rest of analytical parameters studied. Our data demonstrate an association between the C825T polymorphism of the GNB3 and plasma sodium and potassium concentrations in EHP, as expression of an increase in NHE-1 activity, without modifications in PRA nor relationship with salt sensitivity.