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A gender-specific association of the polymorphism Ile197Met in the kininogen 1 gene with plasma irbesartan concentrations in Chinese patients with essential hypertension

Journal of Human Hypertension volume 32, pages 781–788 (2018)Cite this article

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Abstract

This study was conducted to explore interactions in the association of the kininogen (KNG1) Ile197Met polymorphism and gender with plasma concentrations of irbesartan in Chinese patients with essential hypertension. A total of 1100 subjects with essential hypertension received a daily oral dose of 150 mg irbesartan for twenty-eight consecutive days. High-performance liquid chromatography-fluorescence (HPLC) was used to detect plasma irbesartan concentrations on day 28. The KNG1 Ile197Met gene polymorphism was determined using high-throughput TaqMan technology. The frequency distribution of KNG1 Ile197Met genotype conformed to the Hardy-Weinberg equilibrium. After 28 days of treatment, patients with the GG genotype had significantly lower irbesartan concentrations (P = 0.033) compared to homozygous TT genotype carriers. After stratifying by gender, male G allele carriers had significantly lower irbesartan concentrations (GG, P = 0.015; TG, P = 0.015, respectively) relative to TT genotype after adjusting for age, region, body mass index (BMI), smoking, and alcohol consumption. However, there was no significant difference in female subjects. A further test for a multiplicative interaction between the KNG1 Ile197Met polymorphism and gender in association with ln-plasma irbesartan concentrations in a multiple linear regression model was also significant (P for interaction = 0.033). This is the first study to suggest that gender may influence the association of the Ile197Met variant of KNG1 with ln-plasma irbesartan concentration. This finding may indicate that the interaction of gender and the KNG1 Ile197Met gene polymorphism can influence plasma trough irbesartan concentrations, which may contribute to a better development of personalized hypertensive treatment in Chinese patients.

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Acknowledgements

We gratefully acknowledge the assistance and cooperation of the faculty and staff of Anhui Medical University and thank all of the participants in our study. This study was conducted in accordance with the current regulations of the People’s Republic of China.

Funding

This study was supported by the National Natural Science Foundation of China (Grant No. 81373484, 81141116, and 30700454); Open fund for Discipline Construction, Institute of Physical Science and Information Technology, Anhui University; the Academic Top Talents Funding of University (No. gxbjZD2016008) and the Academic Leader and Reserve Candidate of Anhui Province (No. 05010543).

Authors’ contributions:

SH and JC: literature search, collecting data, processing data, data interpretation, analyzing data, and writing manuscript; JW: literature search, data interpretation, and commenting on manuscript; XF: literature search, processing data, and data interpretation; SV: data interpretation and commenting on manuscript; YH: study design, data interpretation, and commenting on manuscript; SW: processing data; FP: study design, data interpretation; JS and SJ: study design, data interpretation, writing manuscript; XX: study design, data interpretation, commenting on manuscript. All authors read and approved the final manuscript.

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  1. These authors contributed equally: Shengnan Hu, Jun Cheng

Authors and Affiliations

  1. School of Life Sciences, Anhui University, Hefei, China

    Shengnan Hu, Jun Cheng, Xiu Fan,  Suwen Wu, Xiangdong Zha & Shanqun Jiang

  2. Institute of Physical Science and Information Technology, Anhui University, Hefei, China

    Shengnan Hu & Shanqun Jiang

  3. Department of Statistics, University of Virginia, Charlottesville, VA, USA

    Justin Weinstock

  4. Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada

    Scott A. Venners

  5. Institute for Aging Research and Harvard Medical School, Boston, MA, USA

    Yi-Hsiang Hsu

  6. Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, Boston, MA, USA

    Yi-Hsiang Hsu

  7. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China

    Faming Pan

  8. Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China

    Jinlu Sun

  9. Institute of Biomedicine, Anhui Medical University, Hefei, China

    Shanqun Jiang & Xiping Xu

  10. National Clinical Research Study Center for Kidney Disease; State Key Laboratory for Organ Failure Research; Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China

    Xiping Xu

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  1. Shengnan Hu
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Correspondence to Jinlu Sun or Shanqun Jiang.

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Hu, S., Cheng, J., Weinstock, J. et al. A gender-specific association of the polymorphism Ile197Met in the kininogen 1 gene with plasma irbesartan concentrations in Chinese patients with essential hypertension. J Hum Hypertens 32, 781–788 (2018). https://doi.org/10.1038/s41371-018-0119-1

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  • DOI: https://doi.org/10.1038/s41371-018-0119-1

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