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.

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. 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. 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). ACE2 SNP rs879922 may be a common genetic loci and optimal genetic susceptibility marker for T2D and T2D related cardiovascular risks in Uygurs.

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. 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. 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. The ACE2 rs4646188 variant may be a potential and optimal genetic susceptibility marker for EH, dyslipidemia and its related ischemic stroke.

Rationale: Colorectal cancer (CRC) is a leading cause of cancer-related mortality. Epigenetic modifications play a significant role in the progression of CRC. KAT7, a histone acetyltransferase, has an unclear role in CRC.

Purpose: Male breast cancer (MBC) is a rare disease that tends to occur in elderly men. Little is known about the causes of death in MBC because of the small sample size of most studies. This study aimed to investigate the causes of death in MBC patients. Patients and Methods: MBC patient data were obtained from the Surveillance, Epidemiology, and End Results database (1975– 2016). Time trends of MBC mortality in the US population were analyzed using Joinpoint software. We calculated the proportion of each cause of death in the overall cohort and in different patient subgroups. Competing risk models were used to calculate cumulative mortality at different follow-up times. The risk of cardiovascular death (CVD) in MBC patients was compared to that of the age-matched general population by calculating standardized mortality ratio (SMR). Results: In total, 6426 patients were included in the analysis. MBC mortality rate increased between 2004 and 2019 (annual percentage change=1.16, 95% confidence interval [CI]: 0.50, 1.80). There were 1757 patients (27.3%) who died of non-breast cancer causes. CVD was the leading cause of death in patients who were elderly or had localized disease. MBC patients had a 6.58-fold higher risk of CVD than the general population (SMR=6.58, 95% CI: 6.14, 7.05). Conclusion: Non-breast cancer death accounts for the majority of deaths in MBC patients who are elderly or have localized cancer. Compared to the general population, MBC patients have an increased risk of CVD. These results highlight the importance of monitoring cardiovascular comorbidities in MBC patients.