scholarly journals Genome-wide association study of angioedema induced by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment

2020 ◽  
Vol 20 (6) ◽  
pp. 770-783 ◽  
Author(s):  
Eva Rye Rasmussen ◽  
Pär Hallberg ◽  
Ekaterina V. Baranova ◽  
Niclas Eriksson ◽  
Malgorzata Karawajczyk ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Association Study ◽  
Candidate Gene ◽  
Angiotensin Receptor Blocker ◽  
Genome Wide Association Study ◽  
Enzyme Inhibitor ◽  
Genome Wide Association ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Genome Wide

AbstractAngioedema in the mouth or upper airways is a feared adverse reaction to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, which is used for hypertension, heart failure and diabetes complications. This candidate gene and genome-wide association study aimed to identify genetic variants predisposing to angioedema induced by these drugs. The discovery cohort consisted of 173 cases and 4890 controls recruited in Sweden. In the candidate gene analysis, ETV6, BDKRB2, MME, and PRKCQ were nominally associated with angioedema (p < 0.05), but did not pass Bonferroni correction for multiple testing (p < 2.89 × 10−5). In the genome-wide analysis, intronic variants in the calcium-activated potassium channel subunit alpha-1 (KCNMA1) gene on chromosome 10 were significantly associated with angioedema (p < 5 × 10−8). Whilst the top KCNMA1 hit was not significant in the replication cohort (413 cases and 599 ACEi-exposed controls from the US and Northern Europe), a meta-analysis of the replication and discovery cohorts (in total 586 cases and 1944 ACEi-exposed controls) revealed that each variant allele increased the odds of experiencing angioedema 1.62 times (95% confidence interval 1.05–2.50, p = 0.030). Associated KCNMA1 variants are not known to be functional, but are in linkage disequilibrium with variants in transcription factor binding sites active in relevant tissues. In summary, our data suggest that common variation in KCNMA1 is associated with risk of angioedema induced by ACEi or ARB treatment. Future whole exome or genome sequencing studies will show whether rare variants in KCNMA1 or other genes contribute to the risk of ACEi- and ARB-induced angioedema.

scholarly journals Common variants near the bradykinin receptor B2 gene are associated with angioedema induced by angiotensin-converting-enzyme inhibitor treatment - a genome wide association study

2020 ◽  
Author(s):  
Jonas Ghouse ◽  
Gustav Ahlberg ◽  
Laura Andreasen ◽  
Karina Banasik ◽  
Søren Brunak ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Converting Enzyme ◽  
Common Variants ◽  
Replication Cohort ◽  
Discovery Cohort ◽  
Genome Wide ◽  
A Genome

ABSTRACTObjectiveAngioedema is a rare, but potentially life-threatening adverse reaction, associated with angiotensin-converting-enzyme inhibitors (ACEi). Identification of potential genetic factors related to this adverse event may help identify at-risk patients.Design, Setting and ParticipantsA genome-wide association study (GWAS) involving patients of European descent, all taking ACEi was conducted in a discovery cohort (Copenhagen Hospital Biobank), and associations were confirmed in a replication cohort (Swedegene). Cases were defined as persons with an angioedema event and a filled prescription for an ACEi 180 days prior to the event. Controls were defined as persons with continuous treatment with ACEi without any history of angioedema. Odds ratios (ORs) and 95 % confidence intervals (95 % CI) were computed for angioedema risk by logistic mixed model regression analysis. Summary statistics from the discovery and the replication cohorts were analyzed with a fixed effects meta-analysis model.ExposureSingle-nucleotide polymorphisms associated with ACEi-associated angioedema.Main outcomeHospital record of angioedema.ResultsThe discovery cohort consisted of 462 cases and 53,391 ACEi-treated controls. The replication cohort consisted of 144 cases and 1,345 ACEi-treated controls. In the discovery cohort, we identified one locus, residing at chromosome 14q32.2, that was associated with angioedema at the genome-wide significance level of P <5 × 10−8. The lead variant at this locus, rs34485356, is an intergenic variant located 60 kb upstream of BDKRB2 (OR 1.62; 95 % CI 1.38 to 1.90; P = 4.3 × 10−9). This variant was validated in our replication cohort with similar direction and effect size (OR 1.60; 95 % CI 1.13 to 2.25; P = 7.2 × 10−3). We found that carriers of the risk allele had significantly lower systolic (−0.46 mmHg per T allele; 95 % CI −0.83 to −0.10; P = 0.013) and diastolic blood pressure (−0.26 mmHg per T allele; 95 % CI −0.46 to −0.05; P = 0.013).ConclusionIn this GWAS, involving individuals treated with ACEi, we found that common variants located in close proximity to the bradykinin receptor B2 gene were associated with ACEi-related angioedema. BDKRB2 genotype-directed therapy may aid in improving safety in evidence-based clinical decision-making.

scholarly journals Genome-Wide Association Study (GWAS) to Identify Salt-Tolerance QTLs Carrying Novel Candidate Genes in Rice During Early Vegetative Stage

Rice ◽  
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Leila Nayyeripasand ◽  
Ghasem Ali Garoosi ◽  
Asadollah Ahmadikhah
Keyword(s):  
Association Study ◽  
Candidate Gene ◽  
Candidate Genes ◽  
Salinity Tolerance ◽  
Genome Wide Association Study ◽  
Dry Weight ◽  
Genome Wide Association ◽  
Vegetative Stage ◽  
Genome Wide ◽  
Genomic Regions

Abstract Background Rice is considered as a salt-sensitive plant, particularly at early vegetative stage, and its production is suffered from salinity due to expansion of salt affected land in areas under cultivation. Hence, significant increase of rice productivity on salinized lands is really necessary. Today genome-wide association study (GWAS) is a method of choice for fine mapping of QTLs involved in plant responses to abiotic stresses including salinity stress at early vegetative stage. In this study using > 33,000 SNP markers we identified rice genomic regions associated to early stage salinity tolerance. Eight salinity-related traits including shoot length (SL), root length (RL), root dry weight (RDW), root fresh weight (RFW), shoot fresh weight (SFW), shoot dry weight (SDW), relative water content (RWC) and TW, and 4 derived traits including SL-R, RL-R, RDW-R and RFW-R in a diverse panel of rice were evaluated under salinity (100 mM NaCl) and normal conditions in growth chamber. Genome-wide association study (GWAS) was applied based on MLM(+Q + K) model. Results Under stress conditions 151 trait-marker associations were identified that were scattered on 10 chromosomes of rice that arranged in 29 genomic regions. A genomic region on chromosome 1 (11.26 Mbp) was identified which co-located with a known QTL region SalTol1 for salinity tolerance at vegetative stage. A candidate gene (Os01g0304100) was identified in this region which encodes a cation chloride cotransporter. Furthermore, on this chromosome two other candidate genes, Os01g0624700 (24.95 Mbp) and Os01g0812000 (34.51 Mbp), were identified that encode a WRKY transcription factor (WRKY 12) and a transcriptional activator of gibberellin-dependent alpha-amylase expression (GAMyb), respectively. Also, a narrow interval on the same chromosome (40.79–42.98 Mbp) carries 12 candidate genes, some of them were not so far reported for salinity tolerance at seedling stage. Two of more interesting genes are Os01g0966000 and Os01g0963000, encoding a plasma membrane (PM) H+-ATPase and a peroxidase BP1 protein. A candidate gene was identified on chromosome 2 (Os02g0730300 at 30.4 Mbp) encoding a high affinity K+ transporter (HAK). On chromosome 6 a DnaJ-encoding gene and pseudouridine synthase gene were identified. Two novel genes on chromosome 8 including the ABI/VP1 transcription factor and retinoblastoma-related protein (RBR), and 3 novel genes on chromosome 11 including a Lox, F-box and Na+/H+ antiporter, were also identified. Conclusion Known or novel candidate genes in this research were identified that can be used for improvement of salinity tolerance in molecular breeding programmes of rice. Further study and identification of effective genes on salinity tolerance by the use of candidate gene-association analysis can help to precisely uncover the mechanisms of salinity tolerance at molecular level. A time dependent relationship between salt tolerance and expression level of candidate genes could be recognized.

scholarly journals Effect of Dual Blockade of Renin-Angiotensin System on Proteinuria

2013 ◽  
Vol 1 (1) ◽  
pp. 18-20
Author(s):  
Eqerem Hasani ◽  
Alma Idrizi ◽  
Myftar Barbullushi
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blocker ◽  
Enzyme Inhibitor ◽  
Combined Therapy ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Dual Blockade

Aim: Aim of the study was the evaluation of the effect of dual blockade of the renin-angiotensin system (RAS) on proteinuria. Material and Methods: Sixty patients, included in the study, were treated with angiotensin-converting enzyme inhibitor and angiotensin receptor blocker for a period of 3 months. Results: The dual blockade of RAS resulted with decrease of proteinuria, a slight increase of serum creatinine and was not associated with a lowering of blood pressure.Conclusion: Combined therapy with ACE-I and ARB results in a more complete blockade of the RAS than monotherapy. In proteinuric nephropathies it reduces significantly baseline proteinuria.

scholarly journals The Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker on the Outcome of Hospitalization of Patients With Hypertension and COVID-19

2021 ◽  
Vol 34 (6) ◽  
pp. 665-666
Author(s):  
Xi-jing Zhuang ◽  
Wen-jun Wang ◽  
Xiao-hui Zhao ◽  
Wei Wei ◽  
Wei-wang Fan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Creatine Kinase ◽  
Angiotensin Converting Enzyme ◽  
Angiotensin Converting Enzyme Inhibitor ◽  
Angiotensin Receptor Blocker ◽  
Enzyme Inhibitor ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Converting Enzyme Inhibitor ◽  
Group A

Abstract Background To study the effect of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) on the outcome of hospitalization in patients with hypertension and novel coronavirus disease 2019 (COVID-19). Methods A retrospective analysis was performed in 202 COVID-19 patients who were hospitalized in Thunder-God Hospital, Wuhan from 12 February 2020 to 30 March 2020. According to whether taking ACEI or ARB, 67 (33.0%) patients with hypertension were divided into 3 groups: A, patients received ACEI or ARB after admission (n = 22); B, patients received ACEI or ARB before admission but interrupted after admission (n = 24); and C, patients were not treated with ACEI or ARB before or after admission (n = 21). Changes of therapeutic indicators in all groups of patients and their application relationship with ACEI/ARB were compared and analyzed. Results There were no significant differences in age, gender, blood pressure, underlying disease severity, or serum biochemical indicators (ALT, LDH, creatinine, and creatine kinase levels) at admission among 3 groups (all P &gt; 0.05). During hospitalization, there were no significant differences in COVID-19-related treatment, oxygen use, hospital mortality, recovery and discharge rate, or days of throat swab nucleic acid turning negative among 3 groups (all P &gt; 0.05). The proportion of calcium channel blocker in groups B and C was higher than group A (95.8% and 85.7% vs. 40.9%, P &lt; 0.01), but there was no significant difference in blood pressure or compliance rates at discharge (P &gt; 0.05). Group A, B, and C patients were hospitalized for 27.4 ± 6.4, 30.0 ± 8.8, and 30.1 ± 9.3 days, respectively (all P &gt; 0.05). Compared with admission values, there were no significant differences in serum ALT, LDH, creatinine, or creatine kinase levels among all 3 groups during hospitalization (all P &gt; 0.05). Conclusions ACEI or ARB has no significant effect on the outcome of hospitalization in patients with hypertension and COVID-19.

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