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Recently in Gut, genetic variation affecting ion channels activity has been highlighted in relation to bowel function and the biology of stool frequency.1 It is also known that 2% of patients with IBS carry functional missense mutations in the voltage-gated channel NaV1.5 (SCN5A gene).2 Hence, channelopathies represent potential abnormalities underlying GI dysfunction and IBS. We inspected data from our previous genome-wide association study (GWAS) of IBS,3 in relation to 27 genes whose ion channel products contribute to GI sensorimotor development and function, visceral sensation and GI motility (see online supplementary table S1). Significant (uncorrected) results were detected for four genes (calcium voltage-gated channels CACNA1A and CACNA1E, and transient receptor potential channels TRPV3 and TRPM8; see online supplementary figure S1), which were selected for replication analyses in an independent set of IBS cases (N=386) and controls (N=357) (see online supplementary material methods). A sex-adjusted logistic regression analysis of genotype data from this cohort (see online supplementary material methods) detected significant associations for …
Footnotes
Contributors MH, AB, GF and MD: study concept and design; TZ, JR, LB, LA, AA, AD, GL, PTS, PK, BO, NJT, MS and SW: characterisation of study individuals, acquisition of data; GA: genotyping; MH, FH, FB and MD: statistical analyses; MH, AB, MW, GF and MD: analysis and interpretation of data; MH, AB, GF and MD: drafting of the manuscript, with critical revision for important intellectual content by all other authors.
Funding This work was supported by grants from The Swedish Research Council (VR 2013-3862) and the Department of Health of the Basque Government (2015111133) to MD. MD and GF are the recipients of a KI-Mayo Collaborative Research Grant for the study of genetic channelopathies in IBS.
Competing interests None.
Ethics approval Karolinska Institutet Ethics Review Board
Provenance and peer review Not commissioned; internally peer reviewed.