Dataset Information

Genetic variation of NEDD4L is associated with essential hypertension in female Kazakh general population: a case-control study.

ABSTRACT: Hypertension affects > 18.8% of adults in China. Indeed, hypertension is the most prevalent risk factor for cardiovascular morbidity and mortality worldwide. Genetic variation is thought to contribute to the etiology of hypertension. NEDD4L is a candidate gene for hypertension, both functionally and genetically. The purpose of the current study was to investigate the relationship between the variation in NEDD4L and essential hypertension in Kazakh, which is a relatively isolated population with a pure genetic background and is an ideal population to study genetic mechanisms of hypertension.We screened the promoter and exons of NEDD4L in 94 Kazakh hypertensive individuals to identify representative variations. Then, by genotyping the representative variations in the Kazakh general population, a case-control study was conducted.By systemically screening variations of NEDD4L, we did not identify any functional mutations in NEDD4L. A new common variation (296921-296923delTTG), which is not found in the NCBI database, was identified. Three representative variations (296921-296923delTTG, rs2288774, and rs2288775) were successfully genotyped in the Kazakh general population. The distribution of the dominant model (AA vs. AG+GG) of rs2288775, the additive model, and the recessive model (II+ID vs. DD) of 296921-296923delTTG differed significantly between the cases and controls in females (P = 0.040, P = 0.024, and P = 0.007, respectively). After adjusting for confounding factors, logistic regression analysis showed that rs2288775 (in the dominant model) and 296921-296923delTTG (in the recessive model) were significantly associated with hypertension (rs2288775: OR = 1.479, 95% CI = 1.011-2.064, p = 0.044; and 296921-296923delTTG: OR = 1.908, 95% CI = 1.020-3.568, p = 0.043) in females. The frequency of the D-C-G haplotype was significantly higher for cases than for controls in females (P = 0.020). There was a significant interaction between the NEDD4L genotype and gender (P for interaction: 0.045 for rs2288775 and 0.064 for 296921-296923delTTG), but there was no significant interaction between the NEDD4L genotype and smoking (P for interaction: 0.616 for rs2288775 and 0.447 for 296921-296923delTTG). For females and total participants, the urinary Na excretion rate was significantly lower in the DD than the I/I+I/D individuals (P = 0.032 and P = 0.027 respectively).The genetic variations of NEDD4L may be associated with essential hypertension in females in the Kazakh general population.

SUBMITTER: Li N

PROVIDER: S-EPMC2801499 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic variation of NEDD4L is associated with essential hypertension in female Kazakh general population: a case-control study.

Li Nanfang N Wang Hongmei H Yang Jin J Zhou Ling L Hong Jing J Guo Yanying Y Luo Wenli W Chang Jianhang J

BMC medical genetics 20091209

<h4>Background</h4>Hypertension affects > 18.8% of adults in China. Indeed, hypertension is the most prevalent risk factor for cardiovascular morbidity and mortality worldwide. Genetic variation is thought to contribute to the etiology of hypertension. NEDD4L is a candidate gene for hypertension, both functionally and genetically. The purpose of the current study was to investigate the relationship between the variation in NEDD4L and essential hypertension in Kazakh, which is a relatively isolat ...[more]

PMID: 20003179

Similar Datasets

Project description:BackgroundGenetic variation is thought to contribute to the etiology of hypertension, and E-selectin is a candidate essential hypertension-associated gene. This study thus sought to investigate possible genetic associations between the T1880C, C602A and T1559C polymorphisms of E-selectin and essential hypertension.MethodsHypertensive patients (n = 490) and healthy normotensive subjects (n = 495) were screened for the genotypes T1880C, C602A and T1559C using real-time quantitative polymerase chain reaction after DNA extraction to identify representative variations in the E-selectin gene. The associations between genotypes and alleles of the three mutations and essential hypertension were then analyzed using a case-control study.ResultsHypertensive patients and normotensive subjects were significantly different with respect to the genotypes CC, CA and AA (P = 0.005) and the C-allele frequency of C602A (P = 0.001). A comparison of dominant versus recessive models also revealed significant differences between the two groups (P = 0.004 and P = 0.02). When subgrouped by gender, these indexes differed significantly between normotensive and essential hypertensive males, but not in females. The additive model of the T1559C genotype did not differ between essential hypertensive and normotensive groups overall (P = 0.39), but it was different between hypertensive and normotensive males (P = 0.046) and females (P = 0.045). The CC + TC versus TT frequency of T1559C was also different in the recessive model of male hypertensive and normotensive groups (P = 0.02). Further analysis showed that C602A and T1559C were significantly associated with hypertension (C602A: OR = 7.58, 95%CI = 1.53-11.97, P < 0.01; and T1559C: OR = 6.77, 95%CI = 1.07-1.83, P < 0.05). The frequency of the C-C-C haplotype was significantly higher in hypertensive patients than in control individuals as well as in hypertensive and normotensive males (P = 0.008 and 0.01). The frequency of the C-A-T haplotype was higher only in male hypertensives and normotensives (P = 0.015). Furthermore, there was a significant interaction between E-selectin and gender (P = 0.02 for C602A and 0.04 for T1559C).ConclusionC602A and T1559C may be independent risk factors for essential hypertension in the Chinese population, whereas T1880C is not.

Project description:Essential hypertension (EH) is influenced by various environmental and genetic factors. Nitric oxide is important for the functional integrity of the vascular endothelium and is produced in endothelial cells by the enzyme endothelial nitric oxide synthase (eNOS). EH has a strong genetic component, and the NOS3 gene, which encodes eNOS, represents an interesting candidate for contribution to the phenotype. The most clinically relevant polymorphisms in the NOS3 gene are rs1799983 in exon 7 (encoding Glu298Asp), a variable number tandem repeat (VNTR) in intron 4, and rs2070744 (T-786C) in the promoter region. This study aims to investigate the association between these three polymorphisms in the NOS3 gene and EH in Sudanese patients.Hypertensive patients (n?=?157) > 18 years of age with established hypertension from various hospitals in Khartoum, and controls (n?=?85) > 18 years of age and with blood pressure measurements <140/90, were included in this case control study. Genotypes at the NOS3 variants were determined using TaqMan and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analyses. Genotype and allele frequencies were compared between the two groups by ?2 analysis, and differences were expressed as odds ratios with 95% confidence intervals (CIs). P values <0.05 were considered statistically significant.The rs2070744 polymorphism in NOS3 was found to be associated with EH in the Sudanese population as the patients group had higher frequency of CC genotype compared with the controls (6.6% vs 6.1%, p?=?0.02). Considering a dominant inheritance model, the frequency of TC + CC genotypes in patients was significantly higher than that in the control subjects (52.6% vs 34.1%, respectively; p < 0.01), with an odds ratio (95% CI) of 2.14 (1.23-3.74). In addition, the C allele was more frequent in the patients than the control group (29.6% vs 20%, p?=?0.03, OR?=?1.84 (1.15-2.93)). The c allele of intron 4 VNTR was reported in >1% of the Sudanese population under study.The results of this study indicated that the rs2070744 polymorphism in NOS3 may be a genetic susceptibility factor for EH in the Sudanese population. The c allele of intron 4 VNTR is not rare in the Sudanese population.

Project description:ObjectiveHere, we aimed to investigate long non-coding RNA (lncRNA) expression characteristics in the peripheral blood lymphocytes of Xinjiang Kazakh people with essential hypertension and the underlying regulatory mechanisms of competing endogenous RNAs (ceRNA).MethodsFrom April 2016 to May 2019, six Kazakh patients with essential hypertension and six Kazakh healthy participants were randomly selected from the inpatient and outpatient cardiology departments of the First Affiliated Hospital of Shihezi University Medical College, Xinjiang. After detecting the expression levels of lncRNA and mRNA in the peripheral blood lymphocytes using gene chip technology, their levels in the hypertensive group were compared with those in the control group. Six differentially expressed lncRNAs were randomly selected for real-time PCR to verify the accuracy and reliability of the gene chip results. GO functional clustering and KEGG pathway analyses were performed for differentially expressed genes. The ceRNA regulatory network of lncRNA-miRNA-mRNA was constructed, followed by visualization of the results. The expressions of miR-139-5p and DCBLD2 after PVT1 overexpression in 293T cells were detected by qRT-PCR and Western blot.ResultsIn the test group, 396 and 511 differentially expressed lncRNAs and mRNAs, respectively, were screened out. The trend of real-time PCR results was consistent with that of the microarray results. The differentially expressed mRNAs were found to be primarily involved in the adhesion spot, leukocyte migration via endothelial cells, gap junction, actin cytoskeleton regulation, and extracellular matrix-receptor interaction signaling pathways. By constructing the ceRNA regulatory network, we found that lncRNA PVT1-miR-139-5p-DCBLD2 has a potential ceRNA regulatory mechanism involved in the development of essential hypertension in Xinjiang Kazakh people. In 293T cells, lncRNA PVT1 overexpression inhibited miR-139-5p and DCBLD2 levels.ConclusionsOur findings indicate that differentially expressed lncRNAs may be involved in the development of essential hypertension. lncRNA PVT1-miR-139-5p-DCBLD2 was indicated to comprise a potential ceRNA regulatory mechanism involved in the development of essential hypertension in the Xinjiang Kazakh population. Thus, it may act as a novel screening marker or therapeutic target for essential hypertension in this population.

Project description:BackgroundAmong Kazakh-Chinese population in Xinjiang province of China, prevalence of obesity and hypertension were 40.1% and 50.3% respectively, the highest across all ethnic groups residing in this pastureland. Despite this, there remained a dearth of information regarding the association between the anthropometric measures [body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), Waist-to-height ratio (WHtR) etc.] and indicators for hypertension control [achieved levels of systolic and diastolic blood pressures (SBP and DBP), pulse pressure index (PPI), ankle-brachial index (ABI) etc.] among them.MethodA cross-sectional study was conducted in Xinjiang to determine the distribution and inter-relationships of the anthropometric measures and indicators for achieved BP control as well as their predictors among hypertension patients of Kazakh-Chinese ethnicity. Out of 550 randomly selected patients, 516 completed the interview, anthropometry and BP assessments.ResultsIn the sample population, average SBP, DBP and PP were 156.26±24.40mmHg, 87.55±14.73mmHg and 68.71±19.39mmHg respectively. Bivariate analysis identified age, gender, education, duration of hypertension, WC and BMI being factors influencing the achieved levels of BP. Adjusted multiple linear regression models elicited positive associations of age (βa = 0.152, p = 0.001) and duration of hypertension (βa = 0.132, p = 0.003) with achieved level of SBP as well as BMI (βa = 0.135, p = 0.002) with DBP. Age (βa = 0.207, p<0.001) and WHtR (βa = 0.304, p = 0.005) were positively and WC (βa = -0.406, p<0.001) was negatively associated with PPI. Increasing age (βa = -0.125, p = 0.005), female gender (βa = -0.122, p = 0.005) and 5years' duration of hypertension (βa = -0.091, p<0.039) were negatively associated with ABI. After adjustment for socio-demographic variables, hypertensive patients with (reference = without) abdominal obesity had 93% (p = 0.013) higher odds of missing the target BP control.ConclusionAnthropometric measures and indicators for blood pressure control among Kazakh-Chinese patients were far beyond normal. Several anthropometric measures appeared useful for monitoring BP. Using them, regular screening and consequent targeted intervention were required urgently to control hypertension among Kazakh-Chinese.

Dataset Information

Genetic variation of NEDD4L is associated with essential hypertension in female Kazakh general population: a case-control study.

Publications

Genetic variation of NEDD4L is associated with essential hypertension in female Kazakh general population: a case-control study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets