scholarly journals Genetic variants associated with angiotensin-converting enzyme inhibitor-induced cough: a genome-wide association study in a Swedish population

2017 ◽  
Vol 18 (3) ◽  
pp. 201-213 ◽  
Author(s):  
Pär Hallberg ◽  
Matilda Persson ◽  
Tomas Axelsson ◽  
Marco Cavalli ◽  
Pia Norling ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Association Study ◽  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Enzyme Inhibitor ◽  
Genome Wide Association ◽  
Converting Enzyme ◽  
Swedish Population ◽  
Genome Wide ◽  
A Genome

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 Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

2017 ◽  
Vol 16 (9) ◽  
pp. 701-711 ◽  
Author(s):  
Davina J Hensman Moss ◽  
Antonio F Pardiñas ◽  
Douglas Langbehn ◽  
Kitty Lo ◽  
Blair R Leavitt ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Association Study ◽  
Huntington’S Disease ◽  
Disease Progression ◽  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome
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