Pharmacogenetics and genomics · 2017
Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors.
СтатьяМетаанализПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Mahmoudpour Seyed H, Veluchamy Abirami, Siddiqui Moneeza K, Asselbergs Folkert W, Souverein Patrick C, de Keyser Catherine E, Hofman Albert, Lang Chim C, Doney Alexander S F, Stricker Bruno H, de Boer Anthonius, Maitland-van der Zee Anke H, Palmer Colin N A, PREDICTION-ADR consortium
Аннотация
OBJECTIVES: To identify single nucleotide polymorphisms (SNPs) associated with switching from an angiotensin-converting enzyme (ACE)-inhibitor to an angiotensin receptor blocker.
METHODS: Two cohorts of patients starting ACE-inhibitors were identified within the Rotterdam Study in the Netherlands and the Genetics of Diabetes Audit and Research in Tayside Scotland study in Scotland. Cases were intolerant patients who switched from an ACE-inhibitor to an angiotensin receptor blocker and controls were individuals who used ACE-inhibitors continuously for at least 2 years and did not switch. Genome-wide association study (GWAS) using an additive model was run in these sets and the results were meta-analysed using Genome-Wide Association Meta Analysis software.
RESULTS: A total of 972 cases out of 5161 ACE-inhibitor starters were identified. Eight SNPs within four genes reached the genome-wide association study significance level (P<5×10) in the meta-analysis [RNA binding protein, Fox-1 homolog (Caenorhabditis elegans), γ-aminobutyric acid receptor subunit γ-2, sarcoma (Src) homology 2 (SH2) B adaptor protein 1 and membrane bound O-acyltransferase domain containing 1]. The strongest associated SNP was located in an intron of RNA binding protein, Fox-1 homolog (Caenorhabditis elegans), which contains an RNA binding protein [rs2061538: minor allele frequency=0.16, odds ratio=1.52 (95% confidence interval: 1.32-1.76), P=6.2×10].
CONCLUSION: These results indicate that genetic variation in the above-mentioned genes may increase the risk of ACE-inhibitor-induced adverse reactions.
METHODS: Two cohorts of patients starting ACE-inhibitors were identified within the Rotterdam Study in the Netherlands and the Genetics of Diabetes Audit and Research in Tayside Scotland study in Scotland. Cases were intolerant patients who switched from an ACE-inhibitor to an angiotensin receptor blocker and controls were individuals who used ACE-inhibitors continuously for at least 2 years and did not switch. Genome-wide association study (GWAS) using an additive model was run in these sets and the results were meta-analysed using Genome-Wide Association Meta Analysis software.
RESULTS: A total of 972 cases out of 5161 ACE-inhibitor starters were identified. Eight SNPs within four genes reached the genome-wide association study significance level (P<5×10) in the meta-analysis [RNA binding protein, Fox-1 homolog (Caenorhabditis elegans), γ-aminobutyric acid receptor subunit γ-2, sarcoma (Src) homology 2 (SH2) B adaptor protein 1 and membrane bound O-acyltransferase domain containing 1]. The strongest associated SNP was located in an intron of RNA binding protein, Fox-1 homolog (Caenorhabditis elegans), which contains an RNA binding protein [rs2061538: minor allele frequency=0.16, odds ratio=1.52 (95% confidence interval: 1.32-1.76), P=6.2×10].
CONCLUSION: These results indicate that genetic variation in the above-mentioned genes may increase the risk of ACE-inhibitor-induced adverse reactions.
Предметные рубрики MeSH
AcetyltransferasesAdaptor Proteins, Signal TransducingAgedAngiotensin-Converting Enzyme InhibitorsAntigens, NuclearDiabetes MellitusFemaleGene FrequencyGene Regulatory NetworksGenome-Wide Association StudyHumansMaleMembrane ProteinsMiddle AgedNerve Tissue ProteinsOdds RatioPolymorphism, Single NucleotideReceptors, GABA-A