Hypertension In Chinese Han Population Research Articles

Relationship of Toll-Like Receptors 2 and 4 Gene Polymorphisms with Essential Hypertension in Chinese Han Population

Objective: There are numerous studies suggesting that genetic polymor-phisms of inflammation factors Toll-like receptors 2 and 4 (TLR2, TLR4) might play a role in the pathophysiological process of hypertension. In this study, we evaluated the association in a sample of members of the Chinese Han population. Method: We selected four single nucleotide polymor-phisms (SNP) of TLR2 (rs3804099, rs3804100, rs7656411) and TLR4 (rs1927906) genes, and measured the distributions of genotypic and allelic frequencies in 1063 participants, including 391 essential hypertension pa-tients and 672 controls. Result: No significant differences in the genotypic and allelic frequencies of the four SNPs were detected between cases and controls. However, three haplotypes, CCG, TTG and TTT of TLR2, were significantly associated with a decrease in the risk of essential hyperten-sion (OR: 0.512, 95% CI: 0.397 - 0.660, P P = 0.0038; OR: 0.797, 95% CI: 0.667 - 0.952, P = 0.0122, respectively). Inversely, the risk of essential hypertension increased sig-nificantly in patients with the CTG, TCG or TCT haplotypes (OR: 2.924, 95% CI: 2.157 - 3.963, P P P TLR2 might have profound effects on the development of essential hypertension in the Chinese Han population.

The association between nicotinamide N-methyltransferase gene polymorphisms and primary hypertension in Chinese Han Population

<abstract> Although no direct evidence shows that Nicotinamide N-methyltransferase (NNMT) is involved in hypertension to date, many reports have shown that NNMT plays important roles in pathogenesis of metabolic syndrome and in various cardiovascular diseases. Here we explored the genetic association between <italic>NNMT</italic> polymorphisms and primary hypertension. 308 primary hypertension cases (aged &lt; 60 years, blood pressure ≥ 140/90 mmHg or taking antihypertensive therapies) and 315 controls (aged ≥ 60 years and without any diagnosed diseases) were recruited from unrelated Chinese Han ethnicity volunteers. Then a case-control study was carried out to explore the genetic association between <italic>NNMT</italic> polymorphism and primary hypertension. A significantly associated SNP (rs1941404) was found in <italic>NNMT</italic> gene (P &lt; 0.0125). At this locus, the risks for minor homozygote CC carriers being of hypertension were highly significantly higher than those for the TT + CT carriers (OR = 2.120, OR_adjusted = 2.573, P = 0.000, P_adjusted = 0.001 and statistical power = 0.997), but the differences between the genotypes CT + CC and TT (dominant genetic model) were not statistically significant (P = 0.321, P_adjusted = 0.230 and statistical power = 0.200). In conclusion, rs1941404 in <italic>NNMT</italic> gene sequence is significantly associated with primary hypertension under a recessive inheritance mode. At this locus, the minor homozygote CC carriers are susceptible population and the TT and CT carriers are non-susceptible population. </abstract>

Association of the interaction between the rs9619311 and rs402007 polymorphisms and smoking with essential hypertension in Chinese Han population.

Background:To assess the association of the interaction between the rs9619311 and rs402007 polymorphisms and smoking with essential hypertension (EH) in a Chinese Han population.Method:Peripheral blood samples were extracted from 422 EH patients and 280 normotensive (NT) patients in a Chinese Han population. A whole blood genomic DNA extraction kit was used to extract genomic DNA from the blood samples. Polymerase chain reaction restriction fragment length polymorphism was used to detect the rs402007 polymorphism of a disintegrin and metalloproteinase with thrombospondin type motifs 1 gene and the rs9619311 polymorphism of the tissue inhibitor of metalloproteinase-3 gene. The distributions of the genotypes and alleles between the 2 study groups (EH and NT) were compared. The main risk factors for EH were determined by using logistic regression analysis. The effects of gene-gene and gene-smoking interactions on EH were analyzed using multifactor dimensional reduction.Results:The frequencies of the rs402007 GC + CC genotype and the C allele were significantly different between the EH and NT groups (0.68 vs 0.57, χ2 = 8.99a, P = .003, odds ratio [OR] = 1.19; 0.45 vs 0.32, χ2 = 22.16a, P < .001, OR = 1.38). The frequencies of the rs9619311 TC + CC genotype and the C allele were also significantly different between the 2 groups (0.33 vs 0.25, χ2 = 4.51a, P = .04, OR = 1.44; 0.18 vs 0.13, χ2 = 7.03a, P = .01, OR = 1.50). Logistic regression analysis suggests that the rs402007 and rs9619311 polymorphisms are independent risk factors for EH (OR = 2.37, 1.86; P < .001, respectively). The multifactor dimensionality redundant analysis results showed that the interaction among rs402007, rs9619311, and smoking was statistically significant (P = .001).Conclusions:A disintegrin and metalloproteinase with thrombospondin type motifs 1 rs402007 and tissue inhibitor of metalloproteinase-3 rs9619311 polymorphisms are associated with EH in a Chinese Han population, and there was a positive interaction among rs402007, rs9619311, and smoking.

KLHL3 single-nucleotide polymorphism is associated with essential hypertension in Chinese Han population.

Hypertension, including secondary and essential hypertension (EH) variants, is a multifactorial disease, affecting more than one billion people worldwide. Secondary hypertension results from mutations in the putative gene KLHL3 (Kelch-like protein 3); however, it has not been reported whether the KLHL3 gene polymorphisms are associated with EH. Here, we investigated the association between KLHL3 (rs2301708 and rs7444370) polymorphisms and EH in the Chinese Han population.This case–control study included 522 subjects—260 patients with EH and 262 normotensive controls matched for age, gender, body mass index (BMI), hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), and levels of Na+, K+, and Cl−. The distribution of functional rs2301708 and rs7444370 polymorphisms within the KLHL3 gene was assessed through polymerase chain reaction (PCR) and restriction-fragment length polymorphism (RFLP).There was no significant difference in allelic and genotypic frequencies of KLHL3 rs2301708 between the EH and normotensive groups; however, the rs7444370 T allele and CT genotype in females was significantly associated with a protective effect against EH (P = .001, P = .002; P = .019, P = .052), and the haplotype CT of rs2301708 and rs7444370 among females in the EH group was less than in the normotensive group (P = .000; P = .007).The KLHL3 rs7444370 variant could be a protective factor in the pathogenesis of females’ EH.

Association between CYP3A4 gene rs4646437 polymorphism and the risk of hypertension in Chinese population: a case-control study.

Using a case–control design, we assessed the association between single nucleotide polymorphisms of CYP3A4 gene rs4646437 polymorphism and the risk of hypertension in Chinese population. We recruited 450 hypertension patients from The First Clinical College, Henan University of Chinese Medicine between June 2017 and May 2018. There was a significant difference in genotype distribution between case group and control group (χ2=18.169, P=0.000). The minor A allele was significantly higher in the case group than that in the control group (31.0 vs 24.8%, P=0.000, odds ratio [OR]=1.36, 95% confidence interval [95% CI]: 1.12–1.66). Significant differences were also observed in other gene models: the GA/AA genotype did not increase the risk of hypertension compared with GG genotype (OR=1.16, 95% CI: 0.90–1.49, P=0.259). Compared with GG/GA genotype, the AA genotype also increased the risk of hypertension (OR=2.34, 95% CI: 1.56–3.50, P=0.000). For additive model, the AA genotype was significantly associated with GG genotype (OR=2.25, 95% CI: 1.49–3.42, P=0.000). The same results were found for AA vs GA (OR=2.50, 95% CI: 1.60–3.89, P=0.000). For the allele genotype, the A allele frequency was significantly higher in the case group than that in the control group (31.0 vs 24.8%, P=0.002). The A allele of CYP3A4 rs4646437 was associated with an increased risk for hypertension (OR=1.36, 95% CI: 1.12–1.66, P=0.002). Our results revealed a possible genetic association between CYP3A4 gene rs4646437 and hypertension, and the AA genotype of rs4646437 increased the risk of hypertension in Chinese Han population, and this effect could be confirmed by multivariable analyses.

Associations between polymorphisms of the CXCL12 and CNNM2 gene and hypertension risk: A case-control study

BackgroundHypertension is the most important risk factor for cardiovascular and cerebrovascular diseases. The study found that CXCL12 and CNNM2 gene affects the risk of coronary heart disease, but the relationship with hypertension is unclear. The aim of this research is to explore the association between CXCL12 and CNNM2 gene and hypertension in Chinese Han population. MethodsGenotypes at 11 CHD-relevant SNPs were determined in 350 Hypertension patients and 483 controls in Chinese Han population using χ2 test, genetic model analysis and haplotype analysis. ResultsIn the allele model, CXCL12 rs1065297 “G” allele, CXCL12 rs4948878 “G” allele and CXCL12 rs10793538 “T” allele were associated with decreased risk of hypertension (rs1065297: OR = 0.53, p = 0.005; rs4948878: OR = 0.51, p = 0.004; rs10793538: OR = 0.58, p = 0.005). CNNM2 rs12413409 “A” allele and CNNM2 rs11191514 “T” allele were also associated with reduced risk of hypertension (rs12413409: OR = 0.71, p = 0.003; rs11191514: OR = 0.70, p = 0.002). Further stratified analysis by sex and age found that CXCL12, CNNM2 gene also influence the risk of hypertension.Model analysis found that CXCL12 rs1093538 TA-TT genotype was associated with decreased risk of hypertension in the dominant model (OR = 0.57, p = 0.0015); Log-additive model revealed that rs1065297 and rs4948878 in CXCL12 gene have a potential association with essential hypertension (rs1065297: OR = 0.54, p = 0.005; rs4948878: OR = 0.52, p = 0.0038). For CNNM2 gene, rs12413409 GA-AA genotype and rs11191514 CT-TT genotype was associated with reduced risk of hypertension in the dominant model (rs12413409: OR = 0.64, p = 0.012; rs11191514: OR = 0.63, p = 0.0082).CXCL12 “GCGCCGT” and CNNM2 “ATAG” haplotype were associated with reduced risk of hypertension with 0.57-fold and 0.75-fold. ConclusionsOur analysis suggests that CXCL12, CNNM2 gene influence the risk of hypertension in Chinese Han population.

Interactions Between PPARG and AGTR1 Gene Polymorphisms on the Risk of Hypertension in Chinese Han Population.

To explore the interactions between PPARG and AGTR1 polymorphisms and their associations with hypertension in the Chinese Han population. Seven single nucleotide polymorphisms (SNPs) of the PPARG gene and five SNPs of the AGTR1 gene were selected and genotyped in 1591 unrelated Chinese Han adults. The SNPAssoc package of R was used to analyze the associations between the selected SNPs and hypertension. The potential gene-gene interactions between PPARG and AGTR1 genes were tested by model-based multifactor dimensionality reduction (MB-MDR). The frequencies of the C allele of rs3856806 and the G allele of rs13433696 in the PPARG gene were significantly lower in hypertensive subjects, whereas the A allele of rs9817428 in the PPARG gene was much higher in hypertensives. In addition, individuals with T allele of rs2933249 in the AGTR1 gene displayed a significantly decreased risk of hypertension. MB-MDR analyses suggested that the two-locus model (rs9817428 and rs2933249) and the three-locus model (rs9817428, rs3856806, and rs2933249) were significantly associated with a decreased risk of hypertension. Moreover, among the eight SNPs not individually associated with hypertension (rs12631819, rs2920502, rs1175543, and rs2972164 in the PPARG gene, and rs2638360, rs1492100, rs5182, and rs275646 in the AGTR1 gene), the two-locus model involving rs12631819 and rs5182 demonstrated increased susceptibility to hypertension, and the five-locus model involving rs12631819, rs2920502, rs2972164, rs5182, and rs2638360 demonstrated a significantly decreased risk of hypertension. Polymorphisms in both the PPARG and AGTR1 genes were found to be significantly associated with hypertension. Moreover, there were significant gene-gene interactions identified between the PPARG and AGTR1 genes in relation to hypertension susceptibility in the Chinese Han population.

Association between CYP3A5 genotypes with hypertension in Chinese Han population: A case-control study

ABSTRACTBackground: The association of CYP3A5 gene polymorphisms with hypertension in the Chinese population is unknown. We explored the association between the CYP3A5 (rs776746) gene and hypertension in the Chinese Han population. Methods: Using a case-control design, 340 cases and 254 controls were enrolled from the Third Affiliated Hospital of South Medical University between July and December of 2015. We used a standardized questionnaire to collect data regarding age, sex, smoking, drinking, family history of hypertension, and physical exercise. Height and weight were measured, and the body mass index (BMI) was calculated by weight/height2. Blood pressure was measured three times after 5 min of rest with at least 15 s between measurements, and the mean was considered the final BP. A Clinical examination was conducted. Results: A total of 594 participants, including 340 cases and 254 controls, were entered into the analyses. The genotype frequencies of the CYP3A5 G>A polymorphism did not deviate from the Hardy-Weinberg equilibrium. The genotype frequencies among the cases were 38.8% (GA, 132 individuals), 42.9% (GG, 146 individuals), and 18.2% (AA, 62 individuals). The differences in genotype between the cases and the controls were statistically significant. The AA genotype was associated with an elevated risk of hypertension after adjusting for potential confounders in Model 2. There was no interaction between smoking and the CYP3A5 genotype, while the interaction between drinking and the CYP3A5 genotype was significant. Conclusion: The CYP3A5 gene may be associated with the risk of hypertension in the Chinese Han population, and this effect may be exacerbated by drinking.

The Hypertension Risk Variant Rs820430 Functions as an Enhancer of SLC4A7.

The large-scale meta-analysis of genome-wide association study (GWAS) recently identified a genomic locus where the genetic variant at rs820430 was strongly associated with hypertension in Chinese Han population, with its T allele conferred increased risks. However, the biological and disease-relevant mechanisms for this association remain elusive. A group of 275 participants from rural district of Shandong Province were enrolled, rs820430 was genotyped using genomic DNA with the fluorogenic 5'-nuclease TaqMan allelic discrimination assay system (Applied Biosystems, CA). In vitro experiments were performed in this study, such as luciferase reporter assays, gel mobility shift assays (electrophoretic mobility shift assay), and chromatin immunoprecipitation. We found the risk T allele of rs820430 was associated with higher SLC4A7 mRNA level in cohort population. Furthermore, we characterized a cis-regulatory mechanism that the T allele of rs820430 distinctively increased c-Fos transcription factor binding, by which leading to increased SLC4A7 expression. The present study indicated that the disease-associated T allele of a new hypertension risk variant rs820430 linked increased hypertension risk through higher SLC4A7 expression, and rs820430 functioned as an enhancer of SLC4A7 transcription by allele distinctively increased c-Fos transcription factor binding.

Case-control study on association of peroxisome proliferator-activated receptor-δ and SNP-SNP interactions with essential hypertension in Chinese Han population.

The aim of this study was to investigate the association of peroxisome proliferator-activated receptor-δ (PPAR-δ) and additional SNP-SNP interaction with essential hypertension (EH) in Chinese Han population. A total of 1248 subjects (625 males, 623 females), including 620 EH patients and 628 normotension subjects, were included in the study. The mean age was 51.2 ± 15.1 years old. Logistic regression model was used to examine the association between four SNP and EH; odds ratio (OR) and 95% confident interval (95%CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze SNP-SNP interaction. EH risk was significantly lower in carriers of C allele of the rs2016520 polymorphism than those with TT (TC + CC versus TT, adjusted OR (95%CI) = 0.61 (0.49-0.78)). In addition, we also found a significant association between rs9794 and EH; EH risk was also significantly lower in carriers of G allele of the rs9794 polymorphism than those with CC (CG + GG versus CC, adjusted OR (95%CI) = 0.65 (0.53-0.83)). We also found a potential SNP-SNP interaction between rs2016520 and rs9794; subjects with TC or CC of rs2016520 and CG or GG of rs9794 genotype have the lowest EH risk, compared to subjects with TT of rs2016520 and CC of rs9794 genotype; OR (95%CI) was 0.32 (0.23-0.62) after covariate adjustment. Our results support an important association between rs2016520 and rs9794 minor allele of PPAR-δ and decreased risk of EH and additional interaction between rs2016520 and rs9794.

GW24-e0355 Clinical Research on Association of CD36 Single Nucleotide Polymorphisms with Essential Hypertension

ObjectivesGenetic mechanisms contribute to blood pressure regulation. This study investigated whether CD36 gene single nucleotide polymorphisms (SNPs) were associated with essential hypertension in Chinese Han population residing in Jilin province.MethodsSNPs...

Associations of MMP1, 3, 9 and TIMP3 Genes Polymorphism with Isolated Systolic Hypertension in Chinese Han Population

Background and aims: Large artery stiffness and endothelial dysfunction are the predominant characteristic of isolated systolic hypertension. Recently studies have revealed MMP1, 3, 9 and TIMP3 Genes polymorphism were associated with arterial stiffness, but the relationship with isolated systolic hypertension were not further studied. This study was to investigate the associations of MMP1,3,9 and TIMP3 Genes polymorphism with isolated systolic hypertension. Methods: We identified the genotype of the genes in 503 patients with isolated systolic hypertension, 481 essential hypertension patients with elevated diastolic blood pressure and 244 age-matched normotensive controls for 5 SNPs and detected the brachial-ankle pulse wave velocity, flow-mediated dilatation, endothelin-1 and nitric oxide among the participants. Results: Multinomial logistic analyses showed that the 5A allele of rs3025058(5A/6A) in MMP3 and the T allele of rs3918242(C-1562T) in MMP9 were significantly associated with isolated systolic hypertension after adjusted by age, triglyceride, low-density lipoprotein (P<0.001, Pcorr<0.003; P=0.009, Pcorr=0.027). The 5A/G/C and 6A/A/T haplotypes were significantly associated with isolated systolic hypertension (Permutation p=0.0258; Permutation p=0.000002). In addition, the brachial-ankle pulse wave velocity of different genotypes for the 5A/6A and C-1562T polymorphisms was significantly highest in 5A or T homozygotes (P<0.01), however, the flow-mediated dilatation and nitric oxide were markedly lowest in 5A or T homozygotes (P<0.01). Conclusion: MMP3 and MMP9 genes variant seem to contribute to the development of isolated systolic hypertension by affecting arterial stiffness and endothelial function.

CLINICAL RESEARCH ON ASSOCIATION OF CD36 SINGLE NUCLEOTIDE POLYMORPHISMS WITH ESSENTIAL HYPERTENSION

ObjectivesGenetic mechanisms contribute to blood pressure regulation. This study investigated whether CD36 gene single nucleotide polymorphisms (SNPs) were associated with essential hypertension in Chinese Han population residing in Jilin province.MethodsSNPs...

Glucose Metabolism in Outpatients with New-Onset Hypertension in Chinese Han Population

The aim of this study was to assess the prevalence of glucose abnormalities in a Chinese Han population with untreated new-onset hypertension. Four hundred and ninety-nine new-onset hypertensive patients without diabetes were enrolled in this study. An abnormal glucose metabolism was diagnosed in 57.1% of the new-onset hypertensive patients without previously diagnosed diabetes. Stratified by age, the prevalence of diabetes and prediabetes were increased with aging. Male sex, advanced age, higher serum triglycerides, and homeostasis model assessment of insulin resistance levels were all significantly associated with the increased risks of pre-diabetes or diabetes in new-onset hypertensive patients when analyzed by the logistic regression analysis.

Gender-specific association between the kininogen 1 gene variants and essential hypertension in Chinese Han population

Kininogens serve as the precursors of potent vasoactive kinin peptides and also function as cysteine proteinase inhibitors. Given its potential role in blood pressure homeostasis, a tagging single nucleotide polymorphism (SNP) based case-control study was conducted to explore the association between kininogen 1 gene common variants and essential hypertension in Chinese Han population. Four tagging SNPs were selected on the basis of the HapMap database and further genotyped in 2411 patients with essential hypertension and 2348 controls from the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA in China). A significant gender-specific association between the kininogen 1 gene common variants and essential hypertension was observed. In male, but not female participants, rs2304456 CC genotype and rs4686799 TT genotype were significantly related to hypertension [odds ratio (OR) = 2.20, 95% confidence interval (CI): 1.24-3.90, P = 0.007 and OR = 1.31, 95% CI: 1.04-1.66, P = 0.025, respectively]. The haplotypes G-C-C-T and the A-A-T-T were significantly associated with essential hypertension in the male population with adjusted OR 1.43 (P < 0.001) and OR 1.24 (P = 0.001), respectively. The haplotype G-A-C-T was in significant association with essential hypertension (OR = 1.42, P = 0.003) as well as systolic blood pressure (P = 0.005) and diastolic blood pressure (P = 0.015). This is the first association study of the kininogen 1 gene with essential hypertension. Both single-locus and haplotype analyses indicated the kininogen 1 gene was associated with essential hypertension and blood pressure traits in the Chinese male population.