To observe the association between uroguanylin G-247A polymorphism and blood pressure/fluid and electrolytes homeostasis.Uroguanylin genotype was determined by restrictive fragment length polymorphism (RFLP) and blood pressure as well as fluid and electrolytes homeostasis were measured in 442 volunteers from Jing Ning County, ZheJiang Province. Data were analyzed by ANOVA, Generalized Estimating Equations (GEE), and Quantitative Transmission Disequilibrium Test (QTDT).Ten uroguanylin gene polymorphisms were detected in 40 subjects by direct sequencing, all were reported in the NCBI SNP database. We selected the G-247A polymorphism for genotyping. Compared with G allele carriers, AA homozygotes had a higher urinary volume (P = 0.08), higher excretions of sodium (P = 0.07) and potassium (P < 0.001), but similar systolic and diastolic blood pressure (P > 0.32) both before and after adjustment for sex, age, body-mass index, current smoking, alcohol intake, and antihypertensive treatment.The uroguanylin G-247A polymorphism was associated with urinary volume and sodium and potassium excretions.
Background: A recent genome-wide linkage study mapped blood pressure (BP)-related loci on human chromosome 1q and identified the regulator of G-protein signaling 5 ( RGS5 ) as a candidate for regulation of BP. Thus, we assessed the relationship between RGS5 genetic polymorphisms and essential hypertension (EH) in Chinese. Methods: A total of 906 patients with EH and 894 age- and gender-matched normotensive (NT) controls were enrolled. Sixteen single nucleotide polymorphisms (SNPs) in RGS5 were genotyped. Results: There were no significant differences in the overall distributions of the genotypic and allelic frequencies for each SNPs between the two groups. However, in haplotype analysis, significant differences for the overall distributions were noted for four haplotypes constructed by five SNPs (rs12041294C/T, rs10917690A/G, rs10917695T/C, rs10917696T/C and rs2662774G/A), viz. H 2 (C–A–C–T–A) (p=0.038), H 5 (C–G–T–T–G) (p=0.001), H 6 (T–G–C–T–A) (p=0.021) and H 12 (T–A–T–T–G) (p=0.023). Serum concentrations of high- and low-density lipoprotein cholesterol showed significant associations with haplotypes revealed by a global test (p=0.0001 and 0.0309). Conclusions: Multiple SNPs in combination in RGS5 may confer risk for hypertension. Our results also lend support for the effect of RGS5 SNPs on lipid metabolism. Further studies are warranted to find the causal SNPs in RGS5 for EH. Clin Chem Lab Med 2009;47:1483–8.
To study the contribution of genetic factors to the variance of serum leptin concentration in healthy, normotensive twins.A total of 57 pairs of twins were investigated: 28 female and 19 male pairs of monozygotic(MZ) twins, and 6 female and 4 male pairs of dizygotic(DZ) twins. The zygosity of twins was determined by comparing the concordance of the genotype of nine fluorescence-labeled microsatellite markers. The genetic analysis was performed using the variance-based method. Serum leptin levels were determined in duplicate by a radioimmunoassay Kit (Linco Research, Inc., St. Charles, Missouri) as previously described.The test of genetic variance revealed a significantly larger within-pair variance of serum leptin in the DZ twins, in comparison with the MZ twins. The corresponding heritability for serum leptin was 8%. Adjusted for BMI, gender, and uric acid (UA), the heritability for serum leptin was 0.18%. Log leptin correlated significantly with blood pressure (SBp r=0.355 P<0.001; DBp r=0.339 P<0.001). Stepwise multiple linear regression analysis revealed that only BMI, gender and UA were linked independently to serum leptin levels(R(2)=0.788, P<0.001).The above data indicate that environmental factors other than genetic factors are important determinants of leptinemia in normal subjects.
OBJECTIVE To identify the genetic variants of angiotensin I converting enzyme 2 (ACE2) gene in a Chinese population and to determine whether the ACE2 gene polymorphisms are associated with essential hypertension (EH). METHODS Seven hundred and forty-five patients with EH and 362 normal blood pressure controls were included in the study to assess the contribution of polymorphism of ACE2 gene. Direct DNA sequencing was performed to detect the single nucleotide polymorphisms (SNPs) in 20 subjects who were randomly selected from the EH patients. RESULTS One SNP named G8790A located in the 4th base of the third intron was found in the 20 patients. The genotyping data indicate that the A allele frequency in male EH patients complicated with cardiac incompetence(55%) is significantly different from that in the control group(43.3%)(P<0.01). The A allele frequency in female patients with cardiac incompetence (56.1%) is higher than that in the controls (50.5%), but the difference does not reach statistical significance. CONCLUSION The G8790A polymorphism may be related to the essential hypertension with cardiac incompetence in Chinese population. Additional investigation will be need to confirm the association.
Objective: To investigate the changes of isomers gene expression about α subunit of sodium pump in cellular membrane during the senescence of human umbilical vein endothelial cells (HUVEC). Methods: A cellular ageing model was built according to extracting, appraising and culturing of the original generation HUVEC. And then it is divided into different groups by giving d-galactose and fragment of extra-cellular segment of sodium pump α subunit (RES ramification) in different PD (Population). The cellular ageing was determined by the intervention of cellular morphology and the dye of senescence associated betad-galactosidase. In addition, the methods of immune cell fluorescence staining, real-time PCR and western blotting were used to analyze the gene expression change of sodium pump α-subunit both in mRNA and protein levels. Results: The expression of sodium pump α1, α2 and α3 unit were all decreased with the increase of the PD in not only mRNA and but also protein levels (Pb0.01); In the same PD, the expression of sodium pump α2 and α3 unit in control group was higher than that in D-galactose group but lower than RES ramification group (Pb0.05). However, there are no significant differences of α1 subunit of sodium pump expression in each group (PN0.05). Conclusions: The unbalanced expression of sodium pump α subunit in cellular membrane may be one of molecular mechanisms of HUVEC aging. It is that the RES ramification plays an important role in defending against the senescence of HUVEC according to recovering the activity of sodium pump α2 and α3 unit partially.
To explore the association of single nucleotide polymorphisms (SNPs) of three candidate genes, including T869C of transforming growth factor beta1 (TGF-beta1), -344T/C of aldosterone synthase (CYP11B2) and Gly460Trp of alpha-Adducin with essential hypertension in Chinese Han population.Three hundred ninety six hypertensive patients and 214 normotensive subjects were genotyped for T869C, -344T/C and Gly460Trp polymorphisms with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and mutagenically separated PCR (MS-PCR), respectively.In single-gene analysis, no association was observed between either CYP11B2 -344T/C or alpha-Adducin Gly460Trp polymorphism and essential hypertension. For female, there were significant difference in genotype distribution and allele frequency of T869C polymorphism (P < 0.02), as compared with subjects with T allele. CC homozygosity had a higher relative risk of hypertension (OR = 2.97, 95% CI, 1.38 to 6.32, P = 0.004), whereas we failed to detect any association between T869C polymorphism and essential hypertension in male. In multiple-gene analysis, the incidence of hypertension was higher in CYP11B2 TT homozygosity than in other CYP11B2 genotypes (OR = 1.99, 95% CI, 1.01 to 3.74, P = 0.03) in the presence of TGF-beta1 CC genotype.Our results indicated that T869C polymorphism of TGF-beta1 gene might be associated with essential hypertension in female, furthermore, the TGF-beta1 T869C and CYP11B2-344T/C polymorphisms appeared to interact in hypertensive population.
To investigate possible association between the single nucleotide polymorphisms (SNPs) of transforming growth factor beta3 (TGF-beta3) gene and essential hypertension (EH) in Chinese.The promoter region, exons, as well as part of the introns of TGF-beta3 gene were sequenced by a fluorescent labeling automatic sequencing method to detect and characterize the SNPs in 24 DNA samples from a Chinese population. Then we conducted a case-control study using 396 patients with hypertension (case) and 214 nomortensive subjects (control). The three SNPs including Thr63Asn, SS5608219 and SS5608220 were genotyped by PCR-RFLP or real-time allele-specific PCR in subjects studied.Seven SNPs in the exons, introns and 3'untranslated region (3'UTR) of TGF-beta3 gene were identified. Among them, 2 SNPs were found to be novel genetic variants and one of the two located in the exon 1 and produced substitution of amino acid. However, no differences were found between hypertensives and nomortensives in genotype distribution and allele frequency of SS5608219, Thr63Asn or SS5608220 polymorphisms.Two novel SNPs of TGF-beta3 gene were identified in Chinese. One of them produces a threonine to asparagines substitution in codon 63 (Thr63Asn). But no association was found between TGF-beta3 gene polymorphisms and EH in Chinese.
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