Biomedical subjects

Yanbin Dong

Publications and source records attributed to Yanbin Dong.

At least 19 recordsLinked to original sources

PubMed2006

Multilocus analyses of Renin-Angiotensin-aldosterone system gene variants on blood pressure at rest and during behavioral stress in young normotensive subjects.

The renin-angiotensin-aldosterone system (RAAS) is a proteolytic cascade that regulates and maintains blood pressure (BP). This study aimed to explore the interactive and integrative effects of multiple RAAS polymorphisms on BP at rest and during behavioral stress in a normotensive population. A total of 920 young white and black twins (age: 12 to 30 years; 45% blacks) was subjected to three 10-minute stress tasks. Thirteen potential functional polymorphisms from 4 major RAAS genes were genotyped. We performed multilocus prediction allowing for genetic modification effects (gene-gene, gene-gender, gene-ethnicity, and gene-body mass index) using Multivariate Adaptive Regression Splines and generalized estimating equations. Single polymorphism analyses showed modest effects of M235T (angiotensinogen) and A-239T (angiotensin I-converting enzyme; P value range: 0.005 to 0.036), accounting for approximately 1% of the total variance of systolic BP at rest and during stress. Compared with this, the best multilocus models revealed multiple independent genetic modification effects (gene-gene, gene-gender, and gene-body mass index; P value range: 0.003 to 0.009), accounting for 2.5% and 7.3% of the total variance for systolic BP levels at rest and during stress, respectively. Our data support the hypothesis that multiple RAAS genetic modifications account for BP variation. We conclude that the RAAS genetic modifications may contribute more to the dynamic BP regulation in response to behavioral stress compared with the static BP value. In addition, we reported a gene-gene interaction between M235T (angiotensinogen) and A1159G (angiotensin I-converting enzyme) on stress systolic BP levels. We proposed a viable approach to test for the multiple genetic contributions to BP and hypertension.

Adolescent↗

PubMed2006

The G protein-coupled receptor kinase 4 gene modulates stress-induced sodium excretion in black normotensive adolescents.

Approximately 20-40% of adolescents have shown a reduction of urinary sodium excretion (U(Na)V) in response to blood pressure (BP) increase during behavioral stress. G protein-coupled receptor kinase 4 (GRK4) mediates the pressure and natriuresis relation. The present study investigated the impact of GRK4 genetic variants on U(Na)V under stress. A total of 664 normotensive adolescents including whites and blacks (17.6 +/- 3.3 yrs, 43.4% blacks) were recruited. Participants were subjected to a stress-protocol including three 10-min tasks (a social competence interview, a virtual reality car driving simulation test, and a video game challenge), concluded by a urine collection. Three functional polymorphisms including R65L, A142V and A486V were genotyped. Given blacks compared with whites had significantly higher systolic BP (SBP) levels during rest (p < 0.001) and stress (p <or= 0.001), there was no statistical difference in U(Na)V in response to stress between the two ethnic groups. In blacks, compared with R65R homozygotes, individuals with R65L or L65L genotype had significantly lower levels of stress-induced U(Na)V (8.42 +/- 0.63 versus 9.85 +/- 0.37 mEq/h, p = 0.01). In summary, BP elevation seems uncoupled with U(Na)V increase during behavioral stress in black adolescents. The 65L allele of the GRK4 gene is associated with stress-induced U(Na)V reduction, suggesting impaired sodium handling in affected black youth.

Adolescent↗

PubMed2006

Update on G-protein polymorphisms in hypertension.

The classic candidate gene approach continues to be the most prevalent tool in the search for the genetic basis of essential hypertension. With the list of candidate genes for this disorder steadily increasing, the pertussis toxin-sensitive inhibitory G protein (Gi) protein beta3 subunit (GNB3) gene has remained "sizzling," challenging the domination of the renin-angiotensin system. Is the genetic variability of GNB3 a causative factor underlying the pathogenesis of essential hypertension? Is the "functional" polymorphism, C825T, only "another" of the countless single nucleotide polymorphisms (SNP) for this disorder after all? As such, does its presence merely reinforce our confidence that essential hypertension is indeed polygenic? Should the C825T polymorphism be used in clinical practice and individualized antihypertensive treatment? Currently, there are still more questions than answers. In this review, in conjunction with our own research, we bring readers up to date on the latest developments of GNB3 polymorphisms in the field of hypertension.

DNA↗

PubMed2006

The G protein-coupled receptor kinase 4 gene affects blood pressure in young normotensive twins.

BACKGROUND: G protein-coupled receptor kinase 4 (GRK4) is involved in activity of dopamine receptors in renal proximal tubules and thus mediates sodium reabsorption and blood pressure (BP) regulation. The present study evaluated the impact of the GRK4 gene variants on BP levels in normotensive adolescents and young adults. METHODS: Three functional polymorphisms of R65L, A142V, and A486V were genotyped in 934 white and African American (44.2%) twin subjects (17.4 +/- 3.4 years of age). A number of association approaches including single-locus analyses, haplotype trend regression analyses, and sib-pair transmission disequilibrium tests were carried out. RESULTS: Single-locus analyses revealed a significant interaction between R65L and age for SBP (P = .019) with an obvious gene-dose effect. In L65L homozygotes SBP showed the steepest increase with age (beta = 0.85, P = .003), R65L heterozygotes showed the next steepest increase (beta = 0.54, P < .001), and the effect of age on SBP was absent in R65R homozygotes. Stratified analyses showed that the SBP increasing effect of the 65L allele was significant only in the older group of subjects (114.1 +/- 11.1 mm Hg v 110.1 +/- 9.6 mm Hg, P = .024). Sib-pair transmission disequilibrium tests analyses in 72 informative dizygotic twin pairs confirmed the significant effect of the 65L on SBP; carriers of the 65L allele had a higher SBP compared with noncarriers (110.3 +/- 8.2 v 107.3 +/- 7.8 mm Hg, P = .047). Haplotype analyses uncovered an interaction between haplotype 65L-142V-486A and age for SBP (P = .017); individuals who were homozygous for haplotype 65L-142V-A486 showed a 1.05-mm Hg steeper increase in SBP per year increase in age compared with those homozygous for the most common R65-A142-A486 haplotype. CONCLUSION: Our data indicate that the R65L polymorphism of the GRK4 gene plays a role in BP regulation in adolescents and young adults.

Adolescent↗

PubMed2006

Effects of dopamine receptor type 1 and Gs protein alpha subunit gene polymorphisms on blood pressure at rest and in response to stress.

BACKGROUND: Exaggerated blood pressure (BP) response to behavioral stress has been recognized as an independent predictor of increased BP levels in human subjects. The coupling of dopamine receptor type 1 (DRD1) with stimulatory G-proteins plays an important role in BP regulation. Therefore, we investigated whether the A-48G polymorphism of the DRD1 gene and the T393C polymorphism of the Gs protein alpha subunit (GNAS) gene influenced BP levels at rest and in response to stress. METHODS: A total of 912 white and African American (44.5%) twin subjects (17.4 +/- 3.4 years) were genotyped. Systolic and diastolic BP were measured at rest and during two 10-min stress tasks (a social competence interview and a virtual reality car driving simulation test). Regular association analyses and sibpair transmission disequilibrium tests were performed. The two polymorphisms, A-48G (DRD1) and T393C (GNAS), were genotyped by polymerase chain reaction with restriction digestion enzymes. RESULTS: A dominant BP-lowering effect of the -48G allele was observed on diastolic BP at rest (P = .032) and in response to the car driving simulation test (P = .046). The 393C allele was associated with higher systolic BP levels during the social competence interview (P = .024) and the car driving simulation test (P = .016). There were no statistical significances between the two loci for systolic and diastolic BP at rest and during stress. CONCLUSIONS: Our findings suggest that DRD1 and GNAS loci contribute to BP regulation at rest, and in particular, in response to behavioral stress. The BP measurement during behavioral stress may have added value for gene association studies.

Adolescent↗

PubMed2006

Effects of angiotensinogen and angiotensin II type I receptor genes on blood pressure and left ventricular mass trajectories in multiethnic youth.

The objective of this study was to evaluate the impact of variations of the angiotensinogen (AGT) and angiotensin II type I receptor (AGTR1) genes on progression of blood pressure (BP) and left ventricular mass (LVM) in multiethnic youth. The study was longitudinal involving 581 European American (EA) and African American (AA) youth with 12 assessments over a 15-year period. AGT M235T and three AGTR1 polymorphisms (C-521T, L191L and A1166C) were genotyped and individual growth curve modeling analyses were conducted. Single nucleotide polymorphism (SNP) analyses found a significant 3-way interaction between M235T, ethnicity and gender on BP levels. Systolic BP (SBP) levels were 5.8 mmHg (p = .00003) and diastolic BP (DBP) levels were 2.6 mmHg (p = .005) lower in carriers versus noncarriers of the M235 allele in AA males only. Furthermore, the AGTR1 L191 allele showed a SBP lowering effect in subjects with a high socioeconomic status (SES;p = .048) and a DBP lowering effect in AAs (p = .038). Haplotype analyses identified a protective haplotype (C-521, 191L and A1166) for LVM levels (p = .03). LVM in individuals homozygous for this haplotype was 12.9 g lower than those homozygous for the most common haplotype (-521T, 191L and A1166). No significant interactions were found between the AGT M235T polymorphism and any of the single SNPs or haplotypes of the AGTR1 gene. Our results in multiethnic youth uncover an ethnicity and gender-specific effect of the AGT M235T polymorphism and a SES or ethnicity-specific effect of the AGTR1 L191L polymorphism on the progression of hypertension risk. A protective AGTR1 haplotype for LVM was also identified.

Adolescent↗

PubMed2005

Adenoviral E1a expression levels affect virus-selective replication in human cancer cells.

One of the promising strategies for targeting replication of oncolytic adenovirus in tumor cells is to regulate the expression of essential viral genes such as E1a by using tumor- or tissue-specific promoters that are preferentially active in cancer cells. However, this approach may lead to some degree of viral replication in normal cells other than in cancer cells if the viral gene also expresses in normal cells. In this study, we investigated the effect of E1a expression levels on the virus replication ability in human cells. Three vectors, all with mutated E1B55K, were created, one without any promoter controlling the E1a gene and two vectors with the E1a gene being controlled by either its endogenous promoter or a strong CMV promoter. We observed that the CMV promoter-mediated high levels of E1A expression could increase virus replication, resulting in the titers of the E1B55K-mutated virus being even higher than the wild-type virus in some cancer cells. However, the strong CMV promoter could not always enhance virus replication, such as in cancer cells OE33 and OsACL. The results suggest that whether increased E1A levels would enhance E1B55K-mutated virus replication may be also depended on cellular factors or pathways in cancer cells. We also observed that the virus without any promoter for the E1a gene could still express leaky levels of E1A which can lead to viral replication in normal and cancer cells. Future efforts in the development of transcription-controlled oncolytic adenoviruses should focus on how to completely block E1a expression in normal cells.

Adenoviridae↗

PubMed2005

Circulating soluble E-selectin levels and the Ser 128Arg polymorphism in individuals from different ethnic groups.

BACKGROUND AND AIM: An association between the Ser128 Arg polymorphism and coronary heart disease (CHD) has been previously demonstrated in a white population. The aim of this study was to investigate whether the Ser128 Arg polymorphism of the E-selectin gene is associated with soluble E-selectin levels in individuals from a multiethnic population. METHODS AND RESULTS: Plasma sE-selectin levels and the Ser128 Arg E-selectin gene polymorphism were determined in 244 white (109 females), 176 of African origin (90 females) and 208 South Asian (95 females) healthy individuals living in England selected from the Wandsworth Heart and Stroke Study (WHSS). The substitution of serine for arginine (A to C mutation) was more common in whites (9.6%) and South Asians (7.9%) compared to the people of African origin (3.7%); p=0.005. The C mutation had no effect on sE-selectin levels in any ethnic group. CONCLUSIONS: We found a lower frequency of this polymorphism in the people of African origin who have a low CHD risk. However, in this study the polymorphism was not associated with circulating sE-selectin levels. Whether it plays a role in determining ethnic differences in vascular disease via a mechanism affecting leukocyte recruitment remains to be determined.

Age Factors↗

PubMed2005

Influence of the eNOS gene on development of blood pressure and left ventricular mass: longitudinal findings in multiethnic youth.

OBJECTIVES: To evaluate the impact of the endothelial nitric oxide synthase (eNOS) gene on longitudinal development of blood pressure (BP) and left ventricular mass (LVM) from childhood into early adulthood. METHODS: Three polymorphisms including -922A>G, intron 4VNTR, and Glu298Asp of the eNOS gene were investigated. Individual growth-curve modeling and haplotype trend regression analyses were conducted for 579 white and black American youths with 12 assessments over a 15-year period. RESULTS: Significantly different allele and genotype frequencies were observed between blacks and whites for all three polymorphisms. Linkage disequilibrium (LD) patterns among these polymorphisms were also different between ethnic groups: strong LD between the -922A>G and intron 4 VNTR loci was observed in whites but not in blacks. Single locus analyses identified a significant interaction between the intron 4 VNTR and gender on diastolic BP (DBP) levels. The 4a allele carriers had significantly lower DBP levels in males (P=0.012), but higher DBP levels in females (P=0.045). Haplotype analyses confirmed the DBP lowering effect in males (P=0.049). DBP in males homozygous for haplotype G-4a-Glu was 2.58 mmHg lower than males homozygous for the most common haplotype (A-non4a-Glu). Additionally, individuals homozygous for haplotype G-non4a-Glu showed a 0.51 mmHg steeper increase in DBP per year with age as compared to the most common haplotype (P=0.007). No associations between single polymorphisms or haplotypes of the eNOS gene and systolic BP or LVM were found. CONCLUSIONS: our results suggest that eNOS gene may have gender-specific and age-dependent effects on DBP and the development of hypertension risk.

Age Factors↗

PubMed2005

Single-strand conformational polymorphism analysis: basic principles and routine practice.

Single-strand conformational polymorphism (SSCP) analysis is a simple and sensitive technique for mutation detection and genotyping. The principle of SSCP analysis is based on the fact that single-stranded DNA has a defined conformation. Altered conformation due to a single base change in the sequence can cause single-stranded DNA to migrate differently under nondenaturing electrophoresis conditions. Therefore wild-type and mutant DNA samples display different band patterns. SSCP analysis involves the following four steps: (1) polymerase chain reaction (PCR) amplification of DNA sequence of interest; (2) denaturation of double-stranded PCR products; (3) cooling of the denatured DNA (single-stranded) to maximize self-annealing; (4) detection of mobility difference of the single-stranded DNAs by electrophoresis under non-denaturing conditions. Several methods have been developed to visualize the SSCP mobility shifts. These include the incorporation of radioisotope labeling, silver staining, fluorescent dye-labeled PCR primers, and more recently, capillary-based electrophoresis. Silver staining is simple, rapid, and cost-effective, and can be routinely performed in clinical laboratories. The use of SSCP analysis to discover and genotype single-nucleotide polymorphisms (SNPs) has been widely applied to the genetics of hypertension, including both monogenic (e.g., Liddle's syndrome) and polygenic disorders (e.g., essential hypertension).

DNA↗

PubMed2005

A gene-environment interaction model of stress-induced hypertension.

The case for a gene-environment interaction model of stress-induced hypertension is detailed in this paper. We hypothesize that repeated exposure to stress in combination with an environmentally and/or genetically mediated susceptibility may lead to the development of essential hypertension. Previously, we reviewed the evidence for a genetic influence on the two major intermediate phenotypes of our model: cardiovascular reactivity to psychological stress and stress-induced sodium retention, representing the cardiovascular and renal stress response, respectively. Here we first describe how genes underlying the physiological systems mediating the stress response of heart, vasculature, and kidney (i.e., the sympathetic nervous system, renin-angiotensin- aldosterone system and sodium reabsorption, and the endothelial system) may increase vulnerability to stress and confer susceptibility to development of essential hypertension. Next, we extend our model and review genes underlying three additional systems that may mediate the influence of stress on the development of essential hypertension: the parasympathetic nervous system, the serotonergic system, and the hypothamamus-pituitary-adrenal axis. The elucidation of our gene-environment interaction model of stress-induced essential hypertension will improve the understanding of the contribution of stress to the development of essential hypertension. This knowledge may lead to more effective primary and secondary prevention programs involving lifestyle interventions in which the role of stress, both acute and chronic, will be taken into account, particularly for individuals at increased genetic risk of essential hypertension.

Animals↗

PubMed2005

Sympathetic nervous system, genes and human essential hypertension.

The sympathetic nervous system (SNS) is the first line of defense in the response to environmental stress through its regulation of second-to-second changes in blood pressure (BP). Both the activity of the SNS and the therapeutic responses to SNS agonists and antagonists are known to be highly variable in the population. "Small" changes caused by single nucleotide polymorphisms (SNPs) of SNS genes may have considerable impact on SNS function and individualized hypertension treatment. In this review, we first describe the physiology of the SNS and its influence on cardiovascular and renal mechanisms of BP regulation. A thorough review of the role of genetic variability of various SNS genes in relation to the development of BP and essential hypertension (EH) follows. Given the vast number of SNS components, evaluations of multiple SNPs from multiple SNS genes are necessary for future association studies of BP and EH. One way to surpass the limitations and inconsistencies of previous association studies is to use a gene-based approach also referred to as indirect association, which takes all common variation within a candidate gene into account. In order to determine how SNS genes are differentially expressed or silenced, activated or inactivated against various environmental backgrounds, it is important to assess not only environmental and lifestyle risk factors such as diet, climate, chronic stress, but also personality characteristics such as hostility and coping styles. Uncovering relevant gene-gene and gene-environment interactions within the SNS cascade will not only enable early detection of EH risk but will also aid in the treatment of hypertensives through both non-pharmacological and pharmacological means.

Animals↗

PubMed2004

Gene expression profiling of E2F-1-induced apoptosis.

It has been shown that adenovirus-mediated overexpression of E2F-1 can efficiently induce apoptosis in cancer cells with little effect on normal cells. However, the mechanisms by which E2F-1 induces apoptosis remains poorly understood. The goal of this study was to evaluate changes in gene expression in response to E2F-1 in order to help elucidate the mechanisms by which E2F-1 causes apoptosis. Therefore, we used a quantitative microarray assay to identify the genes regulated by E2F-1 in melanoma cells. By gene expression profiling, we first screened a proprietary list of about 12,000 genes. Overexpression of E2F-1 in melanoma cells resulted in two-fold or greater alteration in the level of expression of 452 genes compared to vehicle-treated control cells. Most of the affected genes were not known to be responsive to E2F-1 prior to this study. E2F-1 adenoviral infection of these cells was found to affect the expression of a diverse range of genes, including oncogenes, transcription factors and genes involved in signal transduction, cell cycle regulation, cell proliferation and apoptosis, as well as other genes with unknown function. Changes in expression of 17 of these genes were confirmed by quantitative real-time polymerase chain reaction (PCR). This is first application of the microarray technique in the study of the global profile of genes regulated by E2F-1 in melanoma cells. This study leads to an increased understanding of the biochemical pathways involved in E2F-1-induced apoptosis and possibly to the identification of new therapeutic targets.

Adenoviridae↗

PubMed2004

Effects of NOS3 Glu298Asp polymorphism on hemodynamic reactivity to stress: influences of ethnicity and obesity.

Studies on the associations between the nitric oxide synthase gene (NOS3) Glu298Asp polymorphism and hypertension status or blood pressure (BP) levels have had inconsistent results. Potential moderating influences of ethnicity, sex, and obesity on the effects of the NOS3 polymorphism have not been examined. We evaluated the influence of these factors on associations between the NOS3 polymorphism, nitric oxide metabolites (NOx), and hemodynamics at rest and during stress. Subjects were 235 African American (AA) and 262 European American (EA) young adults (18.5+/-2.6 years). Hemodynamic measurements and blood samples for NOx assays were taken before and after a competitive video game challenge. Glu298Asp polymorphism was detected by polymerase chain reaction-restriction enzyme digestion assay. A regression model was built using genotypes, ethnicity, sex, and obesity (body mass index >85th percentile) and their interactions controlling for age; 20.1% of AAs and 49.8% of EAs were carriers of the Asp allele. AAs, regardless of obesity status, exhibited high diastolic blood pressure (DBP) reactivity unless they were nonobese and noncarriers of the Asp allele. EAs exhibited lower DBP reactivity unless they were obese Asp allele carriers. AA nonobese carriers exhibited the greatest total peripheral resistance reactivity. Obese Asp allele carriers exhibited the greatest increases in cardiac output and the greatest decrease in NOx to the stressor. Results indicate the importance of examining impact of BP control-related genetic polymorphisms within the context of moderating factors such as adiposity and ethnicity.

Adolescent↗

PubMed2004

Endothelin-1 gene and progression of blood pressure and left ventricular mass: longitudinal findings in youth.

Endothelin-1 (ET-1) is a powerful vasconstrictor peptide implicated in development of essential hypertension and left ventricular hypertrophy. To evaluate the impact of genetic variability of the ET-1 gene on progression of blood pressure (BP) and left ventricular mass (LVM), we conducted individual growth curve modeling for 537 European American and black youths with 12 assessments during a 15-year period. Four common single-nucleotide polymorphisms (SNPs) including T-1370G, +138/ex1 del/ins, T-37/in2C, and Lys198Asn were included in this study. Single SNP analyses showed that individuals with the +138/ex1 ins allele had a borderline significant lower systolic BP (SBP; P=0.072). Furthermore, the -37/in2C allele showed an SBP-lowering effect in males, accounting for 1.6% between-subject variation of SBP (P=0.016). Haplotype analyses in males confirmed the BP-lowering effect of the -37/in2C allele. SBP in individuals homozygous for the del (+138/ex1) -C (-37/in2) haplotype was 3.3 mm Hg lower than those homozygous for the del (+138/ex1) -T (-37/in2) haplotype (P=0.038). For LVM, we observed a significant gene-environment interaction. LVM levels were 20 g higher in carriers versus noncarriers of the -1370G allele in the low socioeconomic status (SES) group only (P=0.004). In summary, our results uncover a sex-specific protective effect of variation in the ET-1 gene on the progression of hypertension risk, and a SES-specific effect on risk of developing left ventricular hypertrophy in multiethnic youth.

Adolescent↗

PubMed2004

E1A-induced apoptosis does not prevent replication of adenoviruses with deletion of E1b in majority of infected cancer cells.

Apoptotic pathways are initiated as a cellular defense mechanism to eliminate adenovirus-infected cells. We have investigated how E1A-induced apoptosis interferes with viral replication in cancer cells. We found that E1B19K alone can efficiently suppress E1A-induced apoptosis in cancer cells. Viruses deleted for both E1B19K and E1B55K resulted in cellular DNA degradation. However, less than 20% of human lung cancer cells infected with a virus deleted for both E1B19K and E1B55 K had evidence of chromatin condensation and multiple-micronuclei formation (apoptotic hallmarks); these cells could not produce infectious viral particles. The majority of cancer cells infected with viruses deleted for the entire E1b gene did not undergo extended apoptosis and produced abundant viral progeny. Thus, only a fraction of cancer cells underwent apoptosis and did not allow E1b-deleted viruses to replicate, while the majority of cancer cells were resistant to E1A-induced apoptosis and could support virus-selective replication. The results of this study imply that, in addition to inhibiting E1A-induced apoptosis, E1B proteins may contribute other important roles in the viral life cycle. Our results also suggest that combining virus-induced apoptosis and selective viral replication into one vector will be a novel approach to destroy cancer cells.

Adenoviridae Infections↗

PubMed2004

Obesity reveals an association between blood pressure and the G-protein beta3-subunit gene: a study of female dizygotic twins.

The 825C>T polymorphism of the G-protein beta3-subunit gene (GNB3) has been associated with hypertension, although results are not entirely consistent. In a sample of 282 female Caucasian dizygotic twins aged 21-80 years, we aimed to investigate the associations between blood pressure and five single nucleotide polymorphisms (SNPs) including the 825C>T and haplotypes of the GNB3 gene. The polymorphisms (-350A>G, 657A>T, 814G>A, 825C>T and 1429C>T) were genotyped by polymerase chain reaction-restriction enzyme assays. Regular association tests did not show a significant effect on blood pressure for any of the five SNPs. However, strongly significant interactions between the -350A>G, 825C>T and 1429C>T loci and adiposity (both body mass index and waist circumference) were observed for systolic blood pressure (Ps < 0.01) as well as diastolic blood pressure (Ps < 0.05), suggesting increases in adiposity amplify the effects of the SNPs on blood pressure. Haplotype analyses confirmed the effects of the GNB3 gene-obesity interaction on hypertension risk. Additionally, sib-transmission disequilibrium tests (sib-TDTs) showed significant associations with blood pressure for the 825C>T and 1429C>T loci. In summary, the presence of obesity reveals an association between blood pressure and the GNB3 gene in White females. Our data suggest that adiposity is a final pathway through which gene-lifestyle interactions may exert their effects on the development of hypertension. Our results from the combined SNP, haplotype and sib-TDT analyses also support the hypothesis that the 825C>T is a susceptibility locus for hypertension, whereas effects of other loci on blood pressure may result from their strong linkage disequilibrium with the 825C>T locus.

Adult↗

PubMed2004

Molecular variants of the sodium/hydrogen exchanger type 3 gene and essential hypertension.

OBJECTIVES: The objectives of this study were to identify polymorphic variants within the gene coding for the sodium/hydrogen exchanger type 3 (NHE3) and to examine their relationship with hypertension and biochemical indices of sodium balance. DESIGN AND METHODS: Case-control comparisons on a total of 691 subjects of which 399 (68% with essential hypertension) were of African or Afro-Caribbean origin (blacks) and 292 (50% with essential hypertension) were of Caucasian origin (whites). RESULTS: Eight exons of the C terminus of the NHE3 gene were screened systematically. A total of six variants were identified: (G1579A, G1709A, G1867A, C1945T, A2041G and C2405T). Further analyses in relation to essential hypertension and phenotypic characteristics were confined to the more frequent A2041G and the C2405T polymorphisms. The genotype frequencies of the A2041G polymorphism were significantly different between the whites and blacks, with the A allele being more frequent in the white population (0.43 for the whites and 0.14 for the blacks, respectively; P < 0.001). In contrast, there was no significant difference in the C2405T polymorphism between whites and blacks (C allele frequency: 0.86 for the whites and 0.88 for the blacks, respectively). In both the white and the black groups, there were no significant associations between these variants and essential hypertension (P > 0.05) or with serum electrolytes, creatinine or plasma renin activity (PRA) (ANOVA P > 0.05). CONCLUSIONS: These results suggest a high degree of structural conservation of the NHE3 gene; however, the lack of association between these polymorphisms and blood pressure status does not necessarily eliminate the participation of this important sodium/hydrogen exchanger in the pathophysiology of essential hypertension, as we cannot exclude the existence of functionally important genetic variants in other sequences within the NEH3 gene.

Adult↗