Angiotensin-Converting Enzyme Genotype–Specific Immune Response Contributes to the Susceptibility of COVID-19: A Nested Case–Control Study

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has resulted in a global pandemic.Methodology: We used a two-step polymerase chain reaction to detect the ACE genotype and ELISA kits to detect the cytokine factor. We also used proteomics to identify the immune pathway related to the ACE protein expression.Result: In this study, we found that the angiotensin-converting enzyme (ACE) deletion polymorphism was associated with the susceptibility to COVID-19 in a risk-dependent manner among the Chinese population. D/D genotype distributions were higher in the COVID-19 disease group than in the control group (D/D odds ratio is 3.87 for mild (p value < 0.0001), 2.59 for moderate (p value = 0.0002), and 4.05 for severe symptoms (p value < 0.0001), logic regression analysis. Moreover, genotype-specific cytokine storms and immune responses were found enriched in patients with the ACE deletion polymorphism, suggesting the contribution to the susceptibility to COVID-19. Finally, we identified the immune pathway such as the complement system related to the ACE protein expression of patients by lung and plasma proteomics.Conclusion: Our results demonstrated that it is very important to consider gene polymorphisms in the population to discover a host-based COVID-19 vaccine and drug design for preventive and precision medicine.

ACE Genotype Distributions Differ between Sporadic and Familial Hypertrophic Cardiomyopathy

This study investigated the frequency of ACE genotypes in sporadic hypertrophic cardiomyopathy (HCM) and compared these frequencies to those found in the general population and in familial HCM. Delineation of the genotype of a 287 bp fragment in the ACE gene of 10 patients with confirmed sporadic HCM demonstrated that 2 (20%) were of the DD genotype, 5 (50%) of the ID genotype, and 3 (30%) of the II genotype. These genotype distributions did not differ significantly from controls (p < 0.57). Comparison of the present results with genotype frequencies in familial HCM reported in prior studies revealed a significant difference in genotype distribution between sporadic and familial HCM (p < 0.04). These findings indicate that the frequency of the ACE genotype does not appear to differ between patients with sporadic HCM and the general population. However, the results suggest that, with regard to the ACE polymorphism studied, genetic differences may exist between the sporadic and familial forms of HCM.

Hypoxia is not the primary mechanism contributing to exercise-induced proteinuria

IntroductionProteinuria increases at altitude and with exercise, potentially as a result of hypoxia. Using urinary alpha-1 acid glycoprotein (α1-AGP) levels as a sensitive marker of proteinuria, we examined the impact of relative hypoxia due to high altitude and blood pressure-lowering medication on post-exercise proteinuria.MethodsTwenty individuals were pair-matched for sex, age and ACE genotype. They completed maximal exercise tests once at sea level and twice at altitude (5035 m). Losartan (100 mg/day; angiotensin-receptor blocker) and placebo were randomly assigned within each pair 21 days before ascent. The first altitude exercise test was completed within 24–48 hours of arrival (each pair within ~1 hour). Acetazolamide (125 mg two times per day) was administrated immediately after this test for 48 hours until the second altitude exercise test.ResultsWith placebo, post-exercise α1-AGP levels were similar at sea level and altitude. Odds ratio (OR) for increased resting α1-AGP at altitude versus sea level was greater without losartan (2.16 times greater). At altitude, OR for reduced post-exercise α1-AGP (58% lower) was higher with losartan than placebo (2.25 times greater, p=0.059) despite similar pulse oximetry (SpO2) (p=0.95) between groups. Acetazolamide reduced post-exercise proteinuria by approximately threefold (9.3±9.7 vs 3.6±6.0 μg/min; p=0.025) although changes were not correlated (r=−0.10) with significant improvements in SpO2 (69.1%±4.5% vs 75.8%±3.8%; p=0.001).DiscussionProfound systemic hypoxia imposed by altitude does not result in greater post-exercise proteinuria than sea level. Losartan and acetazolamide may attenuate post-exercise proteinuria, however further research is warranted.

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism, Lower Extremity Strength, and Physical Performance in Older Adults

BackgroundEvidence for associations between the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and physical performance is conflicting. Furthermore, investigations of relationships between lower extremity strength and physical performance have usually not considered the role of the ACE genotype, and it is unclear whether there are variations in relationships between lower extremity strength and physical performance among ACE genotypes in older adults.ObjectiveThe objectives of this study were to investigate associations between the ACE I/D polymorphism and physical performance and to determine whether relationships between lower extremity strength and physical performance vary among ACE genotypes in older adults.DesignThis was a cross-sectional observational study.MethodsCommunity-dwelling adults (N = 88) who were at least 60 years old completed physical performance and lower extremity strength tests. After DNA was extracted from saliva, ACE I/D polymorphism genotyping was done. The Spearman rank order correlation coefficient was used to examine associations between lower extremity strength and physical performance within ACE genotype subgroups. Analysis of covariance and linear regression were used to examine ACE genotype and ACE genotype × lower extremity strength interaction effects in relation to physical performance.ResultsGenotype-specific correlation coefficients exhibited substantial variation among ACE genotype subgroups; however, differences did not attain statistical significance. Statistically significant genotype × lower extremity strength interaction effects in relation to physical performance were detected.LimitationsThe cross-sectional design precludes inferring causal relationships between strength and performance. The small sample size contributed to limited power to detect additional interaction effects and to detect statistically significant differences between correlation coefficients among ACE genotype subgroups.ConclusionsThe ACE I/D polymorphism is, interactively with lower extremity strength, associated with physical performance. Genotype-specific correlation coefficients and ACE genotype × lower extremity strength interaction effects on physical performance are consistent with variations in relationships between lower extremity strength and performance among ACE genotype subgroups.

Genetic Variation of I/D Enzyme Converting Angiotensin (ACE) with Athlete Muscle Resistance

Programmed physical exercise in athletes causes the cardiovascular system to be more efficient in pumping blood and carrying oxygen to muscles. Indicators of cardiovascular changes during exercise are: oxygen consumption, heart rate, stroke volume, differences in arterial and venous oxygen, blood pressure and blood flow. Some physical components that need to be considered for development include: VO2 max, muscle endurance, strength, flexibility, speed, stamina, agility, and explosive power. Some specific genes are identified as a muscle phenotype response to strength training, namely angiotensin-converting enzyme (ACE), which converts angiotensin I to angiotensin II. The insertion / deletion (I/D) polymorphism in this gene was found to play a role in variations in the activity of the ACE enzyme, in someone carrying a deletion allele (D) who had higher ACE enzyme activity. The research was carried out at the Organization of the Indonesian National Sports Committee (KONI), especially in South Sulawesi Bangkit athletes. The results showed a significant relationship between genetic variation in ACE gene (I/D) with muscle endurance (p-value 0.05). Likewise in sprints and endurance sports, there was no relationship with variations in the ACE gene (p-value >0.05). In conclusion, further research should be on athletes who win the Olympics or World Championships, with a single sports discipline, larger sample sizes and more diverse genetic variations, so that the ACE genotype can be explored and developed in athletes. Keywords: Athlete, Physical exercise, ACE gene, Genetic variation of I / D, Muscle endurance

The influence of genetic polymorphisms on performance and cardiac and hemodynamic parameters among Brazilian soccer players

This study investigated whether ACTN3 R577X, AMPD1 C34T, I/D ACE, and M235T AGT polymorphisms can affect performance tests such as jumping, sprinting, and endurance in 220 young male athletes from professional minor league soccer team from São Paulo Futebol Clube, Brazil. I/D ACE and M235T AGT polymorphisms were also analyzed according to cardiac and hemodynamic parameters. Athletes were grouped or not by age. DNA from saliva and Taqman assays were used for genotyping 220 athletes and the results were associated with performance tests. Ventricle mass, ventricle end-diastolic diameter, end-diastolic volume, and ejection fraction were assessed by echocardiogram. Arterial pressure, heart rate, and oximetry were assessed by a cardioscope. The main results of this study were that athletes who carried RR/RX (ACTN3) and DD (ACE) genotypes presented better performance during jump and sprint tests. On the other hand, athletes with ID/II genotype presented better results during endurance test, while AGT genotypes did not seem to favor the athletes during the evaluated physical tests. CC genotype (AMPD1) only favored the athletes during 10-m sprint test. Although there are environmental interactions influencing performance, the present results suggest that RR/RX ACTN3 and ACE DD genotypes may benefit athletes in activities that require strength and speed, while II ACE genotype may benefit athletes in endurance activities. This information could help coaches to plan the training session to improve the athletes’ performance.