Association of ACE2 polymorphisms with susceptibility to essential hypertension and dyslipidemia in Xinjiang, China.
ABSTRACT: BACKGROUND:Cardiovascular benefits by reversing environmental risks factors for essential hypertension (EH) and dyslipidemia could be weaken by high genetic risk. We investigated possible associations between ACE2 polymorphisms and dyslipidemia in patients with EH. METHODS:Four hundred and two hypertensive patients were enrolled in an EH group and 233 normotensive individuals were enrolled as control group from the Xinjiang region of China. Fourteen ACE2 polymorphisms were genotyped by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry. RESULTS:Participants carrying T allele (TT?+?CT) of rs2074192 (P?=?0.006), rs4646155 (P?=?0.030) and rs4646188 (P?
Project description:Essential hypertension (EH) is a principal contributing factor in worldwide cardiovascular disease mortality. Although interventions that minimize environmental risk factors for EH are associated with reduced cardiovascular disease, such approaches are limited for individuals with high genetic EH risk. In this study, we investigated possible associations between ACE2 polymorphisms and hypertension-related target organ damages in south Xinjiang, China. Four hundred and two hypertensive patients were enrolled as study participants in an EH group, and 233 normotensive individuals were enrolled as control subjects. Participants were recruited from the south Xinjiang region. Fourteen ACE2 polymorphisms were genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Risk genotypes of rs2074192 (TT+CT, OR?=?1.72, 95% CI: 1.17-2.53), rs2106809 (TT, OR?=?1.71, 95% CI: 1.13-2.58), rs4240157 (CC+CT, OR?=?1.99, 95% CI: 1.17-3.41), rs4646155 (TT+CT, OR?=?1.94, 95% CI: 1.06-3.54), rs4646188 (TT+CT, OR?=?3.25, 95% CI: 1.95-5.41), rs4830542 (CC+CT, OR?=?1.88, 95% CI: 1.10-3.23), and rs879922 (CC+CG, OR?=?4.86, 95% CI: 2.74-8.64) were associated with EH. Hypertensive patients carrying the control genotype of rs2074192 (CC, OR?=?2.37, 95% CI: 1.28-4.39) were associated with CAS ?50%, while those carrying a high-EH-risk genotype of rs4240157 (OR?=?2.62, 95% CI: 1.24-5.54), rs4646155 (OR?=?2.44, 95% CI: 1.16-5.10), or rs4830542 (CC+CT, OR?=?2.20, 95% CI: 1.03-4.69) were associated with atrial fibrillation (AF), larger left atrial diameter, and higher levels of renin-angiotensin-aldosterone system (RAAS) activation (renin and angiotensin I/II). In conclusion, the ACE2 variant rs2074192 was associated with EH and EH with CAS ?50%, while 3 ACE2 variants (rs4240157, rs4646155, and rs4830542) were associated with EH- and hypertension-related AF and left atrial remodeling in south Xinjiang, China.
Project description:The angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis (ACE2-Ang-[1-7]-MAS axis) plays an important role in the control of blood pressure. Some previous studies indicated that the genetic variants of ACE2 may have a potential to influence this axis. Therefore, the present study aimed at examining the association of ACE2 polymorphisms with circulating ACE2 and Ang-(1-7) levels in patients with essential hypertension.Hypertensive patients who met the inclusion criteria were enrolled in the present study. Three Tag single-nucleotide polymorphisms (rs2106809, rs4646155, and rs879922) in ACE2 gene were genotyped for all participants. Circulating ACE2 and Ang-(1-7) levels were detected by enzyme-linked immunosorbent assay.There were 96 (53.0%) females and 85 (47.0%) males participating in the present study. The circulating Ang-(1-7) levels were significantly greater in female patients carrying the rs2106809 CC or CT genotype compared with those carrying the TT genotype (1321.9?±?837.4 or 1077.5?±?804.4?pg/mL vs 751.9?±?612.4?pg/mL, respectively; P = 0.029, analysis of variance), whereas the circulating Ang-(1-7) levels were comparable among genotypes in male patients. In addition, there was no significant difference in the circulating ACE2 levels among rs2106809 CC, CT, and TT genotype groups in both female and male patients. The circulating ACE2 and Ang-(1-7) levels were related to neither rs4646155 nor rs879922 in female or male patients.In conclusion, the rs2106809 polymorphism of the ACE2 gene may be a determinant of the circulating Ang-(1-7) level in female patients with hypertension, suggesting a genetic association between circulating Ang-(1-7) levels and ACE2 gene polymorphisms in patients with hypertension.
Project description:BACKGROUND:Type 2 diabetes mellitus (T2D), rapidly increasing to epidemic proportions, globally escalates cardiovascular disease risk. Although intensive interventions and comprehensive management of environmental risks factors for T2D are associated with reduced cardiovascular disease, such approaches are limited for individuals with high genetic T2D risk. In this study we investigated possible associations of ACE2 polymorphisms and cardiovascular risks in Uygur patients with T2D. METHODS:275 Uygur T2D patients and 272 non-diabetic Uygur individuals were enrolled as study participants. 14 ACE2 polymorphisms were genotyped by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry. RESULTS:ACE2 SNP rs1978124, rs2048683, rs2074192, rs233575, rs4240157, rs4646156, rs4646188 and rs879922 were associated with T2D (all P?<?0.05). The 8 diabetic risk related ACE2 SNPs were further associated with diabetic related cardiovascular complications or events but exhibited heterogeneity as fellows: firstly, almost all diabetic risk related ACE2 SNPs (all P?<?0.05) were associated with increased SBP except rs1978124 and rs2074192, while rs2074192, rs4646188 and rs879922 were associated elevated DBP (all P?<?0.05). Secondly, SNP rs4646188 was not correlated with any type of dyslipidemia (TRIG, HDL-C, LDL-C or CHOL), and the other 7 diabetic risk related loci were at least correlated with one type of dyslipidemia (all P?<?0.05). In particular, rs879922 were simultaneously correlated with four type of dyslipidemia (all P?<?0.05). Thirdly, ACE2 SNP rs2074192 and rs879922 were associated with carotid arteriosclerosis stenosis (CAS)???50% (both P?<?0.05). Fourthly, ACE2 SNP rs2074192, rs4240157, rs4646188 and 879922 were associated with increased MAU (all P?<?0.05). In addition, ACE2 SNP rs2048683, rs4240157, rs4646156, rs4646188 and rs879922 were linked to heavier LVMI (all P?<?0.05), but only rs4240157, rs4646156 and rs4646188 were associated with lower LVEF (all P?<?0.05). CONCLUSION:ACE2 SNP rs879922 may be a common genetic loci and optimal genetic susceptibility marker for T2D and T2D related cardiovascular risks in Uygurs.
Project description:<h4>Background</h4>Atrial fibrillation (AF) is the most common cardiac arrhythmia. Type 2 diabetes (T2D) is an independent risk factor for AF. The cardioembolic stroke (CS) risk is increased when both conditions coexist. Whether angiotensin-converting enzyme 2 (ACE2) genetic variants predict increased risks AF and CS in Uygur patients with T2D remain elusive.<h4>Methods</h4>A total of 547 Uygur subjects (272 controls and 275 T2D patients) were recruited to the study from south Xinjiang. Eight ACE2 variants were identified by MassARRAY system.<h4>Results</h4>ACE2 rs2074192 (CC, adjusted RR?=?2.55, 95% CI 1.35-4.80, P?=?0.004), rs4240157 (CC?+?CT, adjusted RR?=?2.26, 95% CI 1.27-4.04, P?=?0.006) and rs4646188 (TT, adjusted RR?=?2.37, 95% CI 1.16-4.86, P?=?0.018) were associated with higher AF risk. ACE2 rs4240157 (CC?+?CT, adjusted RR?=?2.68, 95% CI 1.36-5.27, P?=?0.004) and rs4646188 (TT, adjusted RR?=?2.56, 95% CI 1.06-6.20, P?=?0.037) were further associated with higher CS risk. The 3 ACE2 variants were related to larger left atrial end-systolic diameter (LAD) (all P?<?0.05), but not all of the 3 ACE2 variants were related to increased levels of serum sodium (rs4240157 and rs4646188, all P?<?0.05), HsCRP (rs4240157 and rs4646188, all P?<?0.05) as well as decreased serum potassium levels (rs2074192 and rs4646188, all P?<?0.05). The 3 ACE2 variants exhibited heterogeneity on circulating RAAS activation. In particular, ACE2 rs4646188 was associated with higher levels of ACE (P?=?0.017 and 0.037), Ang I (P?=?0.002 and 0.001), Ang II (both P?<?0.001) and ALD (P?=?0.005 and 0.011).<h4>Conclusion</h4>These results indicated ACE2 rs4646188 was associated with increased risk of AF and CS among diabetic patients in Uygurs, which could be a promising genetic predisposition marker for early and personalized prevention strategies for the aforementioned clinical pathologies.
Project description:Angiotensin-converting enzyme 2 (ACE2) plays an important role in the development of essential hypertension (EH). The aim of this study was to investigate the relationship of ACE2 gene polymorphisms and enzymatic activity with EH in the northeastern Chinese Han population. 34 single-nucleotide polymorphism (SNP) loci of ACE2 were detected in 1024 EH patients and 956 normotensive (NT) controls by Sequenom Mass-ARRAY RS1000. Five SNPs (rs1514283, rs4646155, rs4646176, rs2285666, and rs879922) in ACE2 gene were determined to significantly associate with EH in female participants, while no SNP locus was linked to male group. Specifically, it was the first time to report that rs4646155 was significantly associated with EH in females. Furthermore, the correlation between ACE2 activity and clinical parameters were performed by Pearson correlation analysis in EH patients. We found that the ACE2 activity level was negatively correlated with body mass index (BMI), DBP, and pulse pressure, and significantly positively with ACE2 concentration, blood glucose and estrogen level in female EH patients. These results demonstrated that the genetic variants of ACE2 played vital roles in the development of EH. And the serum ACE2 activity can predict the development of cardiac dysfunction in EH patients.
Project description:<h4>Background</h4>The ongoing outbreak of SARS-CoV-2 represents a significant challenge to international health. Several reports have highlighted the importance of ACE2 on the pathogenesis of COVID-19. The spike protein of SARS-CoV-2 efficiently binds to the angiotensin-converting enzyme 2 (ACE2) receptors and facilitates virus entry into the host cell. In the present study, we hypothesize that a functional insertion/deletion polymorphism-rs4646994 I/D and rs4240157 T > C in the ACE gene could be associated with SARS-CoV-2 infection and mortality.<h4>Methodology</h4>This study included 117 consecutive COVID-19 patients and 150 age matched healthy controls (ACE2-rs4646994 I/D) and 100 age matched healthy controls with ACE2 rs4240157 T > C. We used Mutation specific PCR (MSP) for ACE2-rs4646994 I/D genotyping and amplification refractory mutation system (ARMS-PCR) for ACE2 rs4240157 T > C genotyping.<h4>Results</h4>Results indicated that there were significant differences in the genotype distributions of ACE2-rs4646994 I/D polymorphisms (<i>p</i> < 0.030) and ACE2 rs4240157 T > C between COVID-19 patients and controls (<i>p</i>-values < 0.05). Higher frequency of DD genotype (48.71%) and D allele (0.67) was reported in COVID-19 patients than controls. Our results showed that the ACE2-DD genotype was strongly associated with increased COVID-19 severity (OR 2.37 (95%) CI = (1.19-4.70), RR = 1.39 (1.09-1.77), <i>p</i> < 0.013) and also a strong association was seen with ACE2-ID genotype with COVID-19 severity (OR 2.20 (95%) CI = (1.08-4.46), <i>p</i> < 0.020) in the codominant model. In allelic comparison, the D allele was strongly associated with COVID-19 severity (OR 1.58 (95% CI) (1.11-2.27), RR 1.21 (1.05-1.41) <i>p</i> < 0.010). A significant correlation of ACE2-I/D genotypes was reported with Age (<i>p</i> < 0.035), T2D (<i>p</i> < 0.0013), hypertension (<i>p</i> < 0.0031) and coronary artery disease (<i>p</i> < 0.0001). Our results indicated ACE2-DD genotype was strongly associated with increased COVID-19 mortality (OR 8.25 (95%) CI = (2.40 to 28.34), <i>p</i> < 0.008) and also ACE2-DD + DI genotype was strongly associated with increased COVID-19 mortality with OR 4.74 (95%) CI = (1.5214 to 14.7915), <i>p</i> < 0.007. A significant correlation was reported between COVID-19 patients and age matched controls (<i>p</i> < 0.0007). Higher frequency of heterozygosity TC (40%) followed by ACE2-CC genotype (24.78%) was reported among COVID-19 patients. Using multivariate analysis, ACE2-CT genotype was strong associated with SARS-CoV-2 severity with an OR 2.18 (95% CI) (1.92-3.99), <i>p</i> < 0.010 and also ACE2-CC genotype was linked with COVID-19 severity with an OR 2.66 (95% CI) (1.53-4.62), <i>p</i> < 0.005. A significant correlation of ACE2-T > C genotypes was reported with gender (<i>p</i> < 0.04), T2D (<i>p</i> < 0.035). ACE2-CC genotype was strongly associated with increased COVID-19 mortality OR 3.66 (95%) CI = (1.34 to 9.97), <i>p</i> < 0.011 and also ACE2-C allele was associated with COVID-19 mortality OR 2, 01 (1.1761-3.45), <i>p</i> < 0.010.<h4>Conclusions</h4>It is concluded that ACE-DD genotype and D allele was strongly associated with increased COVID-19 patient severity. In addition, ACE I/D polymorphism were strongly associated with advanced age, diabetes and ischemic heart disease in COVID-19 patients whereas ACE-II genotype was a protective factor against the development of severe COVID-19. ACE2-DD genotype was strongly associated with increased COVID-19 mortality. Additionally, ACE2-CC and CT genotypes were strongly associated with COVID-19 severity. Therefore, our study might be useful for identifying the susceptible population groups for targeted interventions and for making relevant public health policy decisions.
Project description:Background: Cervical cancer is the second major female cancer in India and constitutes one-fourth of the world's burden. Human Papilloma Virus (HPV) infection is an essential but insufficient cause for cervical cancer. Genetic variants in microRNAs (miRNAs/miRs) play an important role in the susceptibility of various types of cancers.Objective: To evaluate the association of Single Nucleotide Polymorphisms (SNPs) in miR-146a (rs2910164), miR-196a2 (rs11614913), and miR-499 (rs3746444), with cervical cancer susceptibility in Indian population.Methods: Three hundred samples were genotyped by Polymerase chain reaction (PCR)-Restriction fragment length polymorphism (RFLP). Both patients and controls were also screened for the presence of HPV DNA.Results: In this case-control study, 125 (83.3%) cervical cancer cases were found to be infected with HPV DNA. The frequency of miR-146a C allele was higher in controls than in cases [odds ratio (OR) (95% confidence interval (CI)) = 0.81 (0.57-1.14), P-value = 0.258]. miR-196a2 T allele was found to be associated with the decreased risk of cervical cancer [OR (95% CI) = 0.36 (0.26-0.50), P-value<0.0001]. Approximately 1.22-fold increased risk has been observed in individuals carrying miR-499 TT genotypes [OR (95% CI) = 1.22 (0.63-2.36), P-value = 0.617]. Interaction studies for miR-196a2/miR-499 loci showed that women carrying TT/CC and TT/CT genotypes were less likely to develop cervical cancer than CC/CC combination [P<0.05]. Likewise, miR-146a/miR-196a2 genotypic combinations (CC/TT, CG/TT, GG/TT) followed the similar trend [P<0.05], exhibited the protective effect against cervical cancer with reference to CC/CC group. Combined genotypes of miR-146a/miR-499 [CC/CT, CG/CC, CG/CT, CG/TT, GG/CC, GG/CT, GG/TT] demonstrated a non-significant trend toward higher cervical cancer risk [OR > 1.00, P>0.05].Conclusion: Polymorphisms in miR-146a, miR-196a2, and miR-499 individually or collectively have the prospective to emerge as biomarkers for cervical cancer.
Project description:MicroRNAs like miR-143 are increasingly linked to disease pathogenesis. miR-143 is enriched in vascular smooth muscle, and several single nucleotide polymorphisms have been identified in this miRNA. The aim of the current study was to explore a potential correlation between a polymorphism in the miR-143 promoter region, rs4705342, and essential hypertension (EH). Genotyping for miR-143 rs4705342 was performed from blood samples of 156 EH patients (case group) and 187 healthy individuals (control group) using a TaqMan assay. Participant demographic and clinical characteristics were also collected. Logistic regression was used to identify an association between genotype and EH, and odds ratios of EH risk were also determined. Frequencies of the CC, CT, and TT genotypes differed significantly between case (7.7%, 40.4%, 51.9%) and control (15.0%, 48.1%, 36.9%) groups (?(2) = 9.400, P = 0.009). Further, the frequency of the C allele was lower in the case group than in the control group (27.9% vs. 39.0%, P = 0.002). Compared with those having the TT genotype, patients carrying the CC and CT genotypes had a significantly reduced risk for EH (OR = 0.541, 95% CI = 0.351-0.834, P = 0.005), particularly for females, nonsmokers, and those not consuming alcohol (P < 0.05). Thus, the rs4705342 polymorphism in the miR-143 appears to be associated with essential hypertension, and further study is needed to understand the molecular mechanism producing this effect.
Project description:Tumor suppressor p53 directly regulated the abundance of the miR-34b/c. The interaction might contribute to certain cancer. We hypothesized that rs4938723 in the promoter region of pri-miR-34b/c and TP-53 Arg72Pro may be related to the risk of papillary thyroid carcinoma (PTC). A total of 784 patients with PTC and 1006 healthy controls were recruited to participate in this study. The variants were discriminated using a polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Additionally, the relative expression levels of miR-34b/c and TP-53 in 44 paired samples were revealed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A significantly increased risk of PTC was observed in the miR-34b/c rs4938723 CT, CC, and CT/CC genotypes compared with the TT genotype (CT vs TT: adjusted odds ratio [OR]?=?1.51, 95%confidence interval [CI]?=?1.23-1.85; CC vs TT: adjusted OR?=?1.89, 95%CI?=?1.39-2.63; CT/CC vs TT: adjusted OR?=?1.59, 95%CI?=?1.30-1.92, respectively). Significantly increased PTC susceptibility was also associated with the TP-53 Arg72Pro CC and CG/CC genotypes compared with the GG genotype (CC vs GG: adjusted OR?=?2.04, 95%CI?=?1.54-2.70; CG/CC vs GG: adjusted OR?=?1.35, 95%CI?=?1.11-1.67, respectively). Stratification analysis revealed that patients carrying the TP-53 Arg72Pro C allele and CC genotype had a significantly increased risk for developing N1 (C vs. G: OR?=?1.27, 95%CI?=?1.03-1.56; CC vs. GG: OR?=?1.62, 95%CI?=?1.07-2.46, respectively). Combined analysis showed that the genotypes of rs4938723?CT/CC?+?TP-53CG/CC increased the risk of PTC compared with rs4938723TT?+?TP-53GG (OR?=?2.25, 95%CI?=?1.67-3.03). Additionally, level of miR-34b was significantly upregulated in PTC patients.These findings indicate that the miR-34b/c rs4938723 and TP-53 Arg72Pro polymorphisms may contribute to the susceptibility of PTC.
Project description:Objective: Genetic factors are involved in the occurrence, development, and progression of essential hypertension (EH). To study the association between single nucleotide polymorphisms (SNPs) of the rs6435156 and rs1048829 loci of the bone morphogenetic protein receptor type 2 (BMPR2) gene, the rs121909287 and rs121909284 loci of the activin receptor-like kinase 1 (ACVRL1) gene, and the rs397514716 and rs121918359 loci of the mothers against decapentaplegic homolog 9 (SMAD9) gene with the risk of EH in the Chinese Han population. Materials and methods : A total of 460 EH patients and 460 healthy controls were recruited for the study. Genomic DNA of white blood cells was extracted, and the genotypes were analyzed by Sanger sequencing after polymerase chain reaction amplification. Multi-factor dimensionality reduction (MDR) was used to analyze the effect of gene-environment interactions on EH risk. Results: The risk of EH increased in the BMPR2 gene rs6435156 locus dominant model (adjusted odds ratio [OR] = 1.572, 95% confidence interval [CI]: 1.385-1.765, P<0.001) and recessive model (adjusted OR = 1.926, 95% CI: 1.693-2.067, P<0.001). The risk of EH increased in the rs1048829 recessive model (adjusted OR = 1.444, 95% CI: 1.142-1.696, P=0.003). The risk of EH increased in the recessive model of the ACVRL1 gene rs121909287 locus (adjusted OR = 1.403, 95% CI: 1.101-1.660, P=0.008). The risk of EH increased in the SMAD9 gene rs397514716 locus dominant model (adjusted OR = 1.370, 95% CI: 1.183-1.559, P<0.001) and recessive model (adjusted OR = 1.803, 95% CI: 1.470-1.983, P<0.001). The CG haplotype of the rs6435156 and rs1048829 loci of the BMPR2 gene, the CC haplotype of the ACVRL1 gene rs121909287 and rs121909284 loci, and the CC haplotype of the rs397514716 and rs121918359 loci of the SMAD9 gene were factors that protect against EH, whereas the TT haplotype of the rs6435156 and rs1048829 loci in the BMPR2 gene was a risk factor for EH. MDR analysis showed that the BMPR2 gene rs6435156 locus TT genotype carriers, the SMAD9 gene rs397514716 locus TT genotype carriers, and alcohol drinkers had the highest EH risk (OR = 4.523, 95% CI: 2.235-6.871, P<0.001). Conclusion: The SNPs of the rs6435156 and rs1048829 locus in the BMPR2 gene, the rs121909287 loci in the ACVRL1 gene, and the rs397514716 locus in the SMAD9 gene were associated with a risk of EH in Han Chinese.