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J Cell Physiol. 2017 Dec;232(12):3309-3316. doi: 10.1002/jcp.25775. Epub 2017 Apr 10.

KCNQ1 variants associate with hypertension in type 2 diabetes and affect smooth muscle contractility in vitro.

Author information

1
School of Chinese Medicine, China Medical University, Taichung, Taiwan.
2
Department of Integration of Traditional Chinese and Western Medicine, China Medical University Hospital, Taichung, Taiwan.
3
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
4
Biostatistics Center and School of Public Health, China Medical University, Taichung, Taiwan.
5
Biostatistics Center and School of Public Health, Taipei Medical University, Taipei, Taiwan.
6
National Applied Research Laboratories, National Center for High-Performance Computing, Hsinchu, Taiwan.
7
Heart Center, China Medical University Hospital, Taichung, Taiwan.
8
Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
9
Rheumatism Research Center, China Medical University Hospital, Taichung, Taiwan.
10
Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
11
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
12
Department of Cosmetic Science, Providence University, Taichung, Taiwan.
13
Department of Microbiology and Immunology, Chang Gung University, Taoyuan, Taiwan.
14
Graduate Institute of Biostatistics, School of Public Health, China Medical University, Taichung, Taiwan.
15
Graduate Institute of Clinical Medical Science, Chang-Gung University, Taipei, Taiwan.
16
Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.
17
Asia University, Taichung, Taiwan.

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.

KEYWORDS:

KCNQ1; genetic variants; hypertension; muscle contractility; type 2 diabetes

PMID:
28059450
DOI:
10.1002/jcp.25775
[Indexed for MEDLINE]

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