ACE2 polymorphisms associated with cardiovascular risk in Uygurs with type 2 diabetes mellitus.
ABSTRACT: 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?
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: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?<?0.001), C allele (CT?+?CT or CC?+?CG) of rs4240157 (P?=?0.012), rs4830542 (P?=?0.020) and rs879922 (P?<?0.001) and TT genotype of rs2106809 (P?=?0.012) were associated with EH. Meanwhile,ACE2 SNPs also exhibited association with dyslipidemia but exhibited obvious heterogeneity. rs1978124 (TT?+?CT, P?=?0.009), rs2106809 (TT, P?=?0.045), rs233575 (CC?+?CT, P?=?0.018), rs4646188 (CC, P?=?0.011) and rs879922 (CC?+?CG, P?=?0.003) were association with increased LDL-C (?1.8 mmol/L). rs2106809 (CC?+?CT, P?<?0.001), rs2285666(TT?+?CT, P?=?0.017), rs4646142(CC?+?CG, P?=?0.044), rs4646155(TT?+?CT, P?<?0.001) and rs4646188(TT?+?CT, P?=?0.033) were association with decreased HDL-C (<?1.0 mmol/L). rs2074192 (TT?+?CT, P?=?0.012), rs4240157 (CC?+?CT, P?=?0.027), rs4646156 (AA+AT, P?=?0.007), rs4646188 (TT?+?CT, P?=?0.005), rs4830542 (CC?+?CT, P?=?0.047) and rs879922 (CC?+?CG, P?=?0.001) were association with increased TC (?5.2 mmol/L). rs2106809 (P?=?0.034) and rs4646188 (P?=?0.013) were associated with hypertriglyceridemia. Further, ischemic stroke was more prevalent with rs4240157 (CC?+?CT, P?=?0.043), rs4646188 (CC?+?CT, P?=?0.013) and rs4830542 (CC?+?CT, P?=?0.037). In addition, rs2048683 and rs6632677 were not association with EH, dyslipidemia and ischemic stroke. CONCLUSION:The ACE2 rs4646188 variant may be a potential and optimal genetic susceptibility marker for EH, dyslipidemia and its related ischemic stroke.
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:To examine the association of Angiotensin I converting enzyme 2 (ACE2) gene polymorphisms and retinopathy in a Chinese type 2 diabetes mellitus (T2DM) cohort.A total of 743 T2DM participants were involved in this study including 408 female and 335 male cases. Female cases were divided into two groups: diabetes without retinopathy (DNR group, n=171) and with retinopathy (DR group, n=237), the latter was further subclassified into nonproliferative DR (NPDR group, n=121) and proliferative DR (PDR group, n=116). Male cases were assigned to DNR group (n=153) and DR group (n=182) which was further grouped into NPDR group (n=86) and PDR group (n=96). Two single nucleotide polymorphisms (SNPs; rs2074192 and rs714205) in ACE2 gene were genotyped.In female cases, the frequency of genotypes TT in rs2074192 and CC in rs714205 were higher in DR and PDR group than in DNR group (P<0.05). The frequency of alleles T in SNP rs2074192 and C in SNP rs714205 was higher in DR group (P<0.05) and PDR group (P<0.05) than in DNR group. The frequency of allele T in SNP rs2074192 was higher in PDR group (P=0.04) than in NPDR group. The frequency of haplotype TC and CG was higher in DR and PDR groups, respectively (P<0.05). No positive results were found in male cases.Our results revealed that SNPs rs2074192 and rs714205 in ACE2 gene were associated with the susceptibility of DR and PDR.
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: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: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:SNP rs2943641 near the insulin receptor substrate 1 (IRS1) gene has been found to be associated with type 2 diabetes (T2D) and insulin-resistance in genome-wide association studies. We investigated whether this SNP is associated with cardiovascular risk factors and coronary artery disease (CAD) among diabetic individuals.SNP rs2943641 was typed in 2133 White T2D subjects and tested for association with BMI, serum HDL cholesterol and triglycerides, hypertension history, and CAD risk.HDL cholesterol decreased by 1mg/dl (p = 0.004) and serum triglycerides increased by 6 mg/dl (p = 0.016) for each copy of the insulin-resistance allele. Despite these effects, no association was found with increased CAD risk (OR = 1.00, 95% CI 0.88-1.13).The insulin-resistance and T2D locus near the IRS1 gene is a determinant of lower HDL cholesterol among T2D subjects. However, this effect is small and does not translate into a detectable increase in CAD risk in this population.
Project description:The Angiotensin-Converting Enzyme-2 (ACE2) gene, located on chromosome X, is believed to be implicated in blood pressure regulation. However the few studies that have examined this association have yielded mixed results. The objective of this study was to assess the association between tag single nucleotide polymorphisms (SNPs) in the angiotensin-converting enzyme-2 gene with blood pressure and blood pressure change in adolescents.Participants in the Nicotine Dependence in Teens (NDIT) cohort study with blood or saliva samples and at least 3 blood pressure measurements over 5 years were included in the analytic sample (n?=?555). Linear growth curve models stratified on sex and ethnicity were used to assess the association between four tag SNPs in the ACE2 gene and systolic (SBP) and diastolic blood pressure (DBP), and blood pressure change.In males of European descent, rs2074192 and rs233575 were significantly associated with SBP and DBP, and rs2158083 was associated with SBP. In French Canadian males, rs233575 and rs2158083 were significantly associated with DBP. Among females of European descent, rs2074192, rs233575, and rs2158083 were significantly associated with change in SBP over 5 years.This is the first study to assess the association between the ACE2 gene with blood pressure and blood pressure change in a cohort of adolescents. Results indicate that several ACE2 gene SNPs are associated with blood pressure or blood pressure change in persons of European descent. However the therapeutic potential of these SNPs should be explored.
Project description:OBJECTIVE:To investigate the correlation of macrophage inflammatory protein-1? (MIP-1?) gene single nucleotide polymorphisms (SNP) with the susceptibility to pigeon breeder's lung (PBL) in Chinese Uygur population. METHODS:A total of 92 Uygur from Xinjiang, China were enrolled in the study. Among them, there were 32 patients with PBL, 30 negative controls with history of exposure to pigeons and 30 normal controls without pigeons contact. SNP genotyping for 24 SNPs of MIP-1? were performed. RESULTS:Genotype distribution of MIP-1? SNPs rs1049191, rs1049195, rs3210166, rs1130374 and rs5029407 were significantly different among the three groups (P<0.05). CONCLUSION:MIP-1? SNPs rs1049191, rs1049195, rs3210166, rs1130374 and rs5029407 might have correlation with the susceptibility to pigeon breeder's lung in Chinese Uygur population.