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The E23K and A190A variations of the KCNJ11 gene are associated with early-onset type 2 diabetes and blood pressure in the Chinese population

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Abstract

Conflicting associations between define (KCNJ11) variations and susceptibility to late-onset (>40 years old) type 2 diabetes mellitus (T2DM) have been reported in different ethnic groups. We investigated whether the E23K (G→A, rs5219) or A190A (C→T, rs5218) variations in KCNJ11 are associated with early-onset T2DM and blood pressure in the Chinese population. Case-control study of 175 unrelated Chinese patients with early-onset T2DM (age of onset <40 years old) who receive (ins+, n = 57) or do not receive insulin (ins−, n = 118), and 182 non-diabetic control subjects. PCR-direct sequencing was performed to genotype E23K and A190A; the genotypic frequencies and associations with clinical characteristics were analyzed. The genotypic frequencies of E23K-GA+AA were higher and A190A-TT was lower in the early-onset T2DM group, especially the T2D-ins+ group, compared to the non-diabetic control group (p < 0.01 or 0.05, respectively). In non-diabetic subjects, E23K-AA carriers had significantly higher 2 h plasma glucose and lower 2 h insulin than E23K-GG carriers (both p < 0.05). A190A-TT or E23K-GG carriers had higher systolic blood pressure (SBP) than CC or AA carriers in the non-diabetic control and T2DM groups (both p < 0.05). In the T2DM ins+ group, E23K-AA carriers had lower onset age and duration of diabetes and higher BMI than GG carriers, and A190A-TT carriers had higher SBP than CC carriers (all p < 0.05). The E23K-GA or AA genotypes may increase the susceptibility to early-onset T2DM, while A190A-TT may protect against early-onset T2DM. On the other hand the A190A-TT or E23K-GG genotypes may increase the risk of hypertension in the Chinese population.

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Acknowledgments

This research was supported by Grants from the Project of National Natural Science Foundation of China (Nos. 81471012, 81270876, 30771022, and 30971384) and the Shanghai Scientific & Technical Committee Foundation (Nos. 10XD1403400 and 06ZR14051). YL was supported by NIH Grant SC1DK087655 and SC1DK104821.

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Authors and Affiliations

  1. Department of Endocrinology & Metabolism, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai Diabetes Institute, 600 Yishan Road, Shanghai, 200233, China

    Langen Zhuang, Weijing Zhao, Ming Li, Rong Zhang, Xiaoxu Ge, Taishan Zheng, Can Li, Jun Yin, Yuqian Bao, Limei Liu & Weiping Jia

  2. Department of Endocrinology, Inner Mongolia General Forestry Hospital, Yakeshi, Inner Mongolia, China

    Yu Zhao

  3. Department of Endocrinology & Metabolism, Putuo Hospital Attached to Shanghai University of Traditional Chinese Medicine, Shanghai, China

    Ming Yu & Ming Lu

  4. School of Computer Engineering and Science, Shanghai University, Shanghai, China

    Jingyuan Yin

  5. Division of Endocrinology, UCLA School of Medicine, Charles R. Drew University of Medicine & Sciences, Los Angeles, CA, USA

    Yanjun Liu

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  1. Langen Zhuang
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Correspondence to Limei Liu.

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Langen Zhuang, Yu Zhao and Weijing Zhao have contributed equally to this work.

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Zhuang, L., Zhao, Y., Zhao, W. et al. The E23K and A190A variations of the KCNJ11 gene are associated with early-onset type 2 diabetes and blood pressure in the Chinese population. Mol Cell Biochem 404, 133–141 (2015). https://doi.org/10.1007/s11010-015-2373-7

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