title: KCNQ1 variants associate with hypertension in type 2 diabetes and affect smooth muscle contractility in vitro.
abstract: KCNQ1 encodes a potassium voltage-gated channel and represents a susceptibility locus for type 2 diabetes mellitus (T2DM). Here, we explored the association between KCNQ1 polymorphisms and hypertension risk in individuals with T2DM, as well as the role of KCNQ1 in vascular smooth muscle cell contraction in vitro. To investigate the relationship between KCNQ1 and the risk of developing hypertension in patients with T2DM, we divided the T2DM cohort into hypertension (n = 452) and non-hypertension (n = 541) groups. The Mann-Whitney U test, chi-square test, and multivariate regression analyses were used to assess the clinical characteristics and genotypic frequencies. In vitro studies utilized the rat aortic smooth muscle A10 cell line. Patients in the hypertension group were significantly older at the time of enrollment and had higher levels of body mass index, waist-to-hip ratio, and triglyceride than those in the non-hypertension group. The KCNQ1 rs3864884 and rs12576239 genetic variants were associated with hypertension in T2DM. KCNQ1 expression was lower in the individuals with the CC versus the CT and TT genotypes. Smooth muscle cell contractility was inhibited by treatment with a KCNQ1 inhibitor. These results suggest that KCNQ1 might be associated with hypertension in individuals with T2DM.
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.|Department of Integration of Traditional Chinese and Western Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Kuo-Chin
authors.initials: KC
authors.lastname: Huang
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Te-Mao
authors.initials: TM
authors.lastname: Li
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Biostatistics Center and School of Public Health, China Medical University, Taichung, Taiwan.|Biostatistics Center and School of Public Health, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Chen
authors.affiliation: National Applied Research Laboratories, National Center for High-Performance Computing, Hsinchu, Taiwan.
authors.forename: Wen-Kuei
authors.initials: WK
authors.lastname: Chien
authors.affiliation: Heart Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yi-Tzone
authors.initials: YT
authors.lastname: Shiao
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Hsinyi
authors.initials: H
authors.lastname: Tsang
authors.affiliation: Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Ting-Hsu
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chiu-Chu
authors.initials: CC
authors.lastname: Liao
authors.affiliation: Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Shao-Mei
authors.initials: SM
authors.lastname: Huang
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.|Rheumatism Research Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Ju-Pi
authors.initials: JP
authors.lastname: Li
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Lin
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jung-Chun
authors.initials: JC
authors.lastname: Lin
authors.affiliation: Department of Cosmetic Science, Providence University, Taichung, Taiwan.
authors.forename: Chih-Chien
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Microbiology and Immunology, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chih-Ho
authors.initials: CH
authors.lastname: Lai
authors.affiliation: Graduate Institute of Biostatistics, School of Public Health, China Medical University, Taichung, Taiwan.
authors.forename: Chi-Fung
authors.initials: CF
authors.lastname: Cheng
authors.affiliation: Graduate Institute of Biostatistics, School of Public Health, China Medical University, Taichung, Taiwan.
authors.forename: Wen-Miin
authors.initials: WM
authors.lastname: Liang
authors.affiliation: Graduate Institute of Clinical Medical Science, Chang-Gung University, Taipei, Taiwan.
authors.forename: Chien-Hui
authors.initials: CH
authors.lastname: Hung
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.|Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Ching-Chu
authors.initials: CC
authors.lastname: Chen
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.|Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Ying-Ju
authors.identifier: http://orcid.org/0000-0003-4684-0585
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.|Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.|Asia University, Taichung, Taiwan.
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
mesh_terms: D000368:Aged; D000818:Animals; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics*; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000502:physiology*; D051381:Rats
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C496911:Kcnq1 protein, rat
keywords: KCNQ1; genetic variants; hypertension; muscle contractility; type 2 diabetes