A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough

作者：Mosley J D; Shaffer C M; Van Driest S L; Weeke P E; Wells Q S; Karnes J H; Edwards D R Velez; Wei W Q; Teixeira P L; Bastarache L; Crawford D C; Li R; Manolio T A; Bottinger E P; McCarty C A; Linneman J G; Brilliant M H; Pacheco J A; Thompson W; Chisholm R L; Jarvik G P; Crosslin D R; Carrell D S; Baldwin E; Ralston J; Larson E B; Grafton J; Scrol A; Jouni H; Kullo I J; Tromp G; Borthwick K M; Kuivaniemi H

来源：The Pharmacogenomics Journal, 2016, 16(3): 231-237.

DOI：10.1038/tpj.2015.51

The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough. Controls were subjects with at least 6 months of ACEi use and no cough. A GWAS (1595 cases and 5485 controls) identified associations on chromosome 4 in an intron of KCNIP4. The strongest association was at rs145489027 (minor allele frequency = 0.33, odds ratio (OR) = 1.3 (95% confidence interval (CI): 1.2-1.4), P = 1.0 x 10(-8)). Replication for six single-nucleotide polymorphisms (SNPs) in KCNIP4 was tested in a second eMERGE population (n = 926) and in the Genetics of Diabetes Audit and Research in Tayside, Scotland (GoDARTS) cohort (n = 4309). Replication was observed at rs7675300 (OR = 1.32 (1.01-1.70), P = 0.04) in eMERGE and at rs16870989 and rs1495509 (OR = 1.15 (1.01-1.30), P = 0.03 for both) in GoDARTS. The combined association at rs1495509 was significant (OR = 1.23 (1.15-1.32), P = 1.9 x 10(-9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk.

• 出版日期2016-6
• 单位西北大学