Association of circadian genes with diurnal blood pressure changes and non-dipper essential hypertension: A genetic association with young-onset hypertension

Hsin Bang Leu, Chia Min Chung, Shing Jong Lin, Kuang Mao Chiang, Hsin Chou Yang, Hung Yun Ho, Chih Tai Ting, Tsung Hsien Lin, Sheng Hsiung Sheu, Wei Chuan Tsai, Jyh Hong Chen, Wei Hsian Yin, Ting Yu Chiu, Chin Iuan Chen, Cathy Sj Fann, Yuan Tsong Chen, Wen Harn Pan, Jaw Wen Chen

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18 Citations (Scopus)

Abstract

Recent studies have suggested that circadian genes have important roles in maintaining the circadian rhythm of the cardiovascular system. However, the associations between diurnal BP changes and circadian genes remain undetermined. We conducted a genetic association study of young-onset hypertension, in which 24-h ambulatory blood pressure (BP) monitoring was performed. A total of 23 tag single-nucleotide polymorphisms (SNPs) on 11 genes involved in circadian rhythms were genotyped for correlations with diurnal BP variation phenotypes. A permutation test was used to correct for multiple testing. Five tag SNPs within five loci, including rs3888170 in NPAS2, rs6431590 in PER2, rs1410225 in RORββ, rs3816358 in BMAL1 and rs10519096 in RORα, were significantly associated with the non-dipper phenotype in 372 young hypertensive patients. A genetic risk score was generated by counting the risk alleles and effects for each individual. Genotyping was performed in an additional independent set of 619 young-onset hypertensive subjects. Altogether, non-dippers had a higher weighted genetic risk score than dippers (1.67±0.56 vs. 1.54±0.55, P<0.001), and the additive genetic risk score also indicated a graded association with decreased diurnal BP changes (P=0.006), as well as a non-dipper phenotype (P=0.031). After multivariable logistic analysis, only the circadian genetic risk score (odds ratio (OR), 1550; 95% confidence interval (CI), 1.225-1.961, P<0.001) and the use of β-blockers (OR, 1.519; 95% CI, 1.164-1.982, P=0.003) were independently associated with the presence of non-dippers among subjects with young-onset hypertension. Genetic variants in circadian genes were associated with the diurnal phenotype of hypertension, suggesting a genetic association with diurnal BP changes in essential hypertension.

Original languageEnglish
Pages (from-to)155-162
Number of pages8
JournalHypertension Research
Volume38
Issue number2
DOIs
Publication statusPublished - 2015 Feb 7

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Leu, H. B., Chung, C. M., Lin, S. J., Chiang, K. M., Yang, H. C., Ho, H. Y., Ting, C. T., Lin, T. H., Sheu, S. H., Tsai, W. C., Chen, J. H., Yin, W. H., Chiu, T. Y., Chen, C. I., Fann, C. S., Chen, Y. T., Pan, W. H., & Chen, J. W. (2015). Association of circadian genes with diurnal blood pressure changes and non-dipper essential hypertension: A genetic association with young-onset hypertension. Hypertension Research, 38(2), 155-162. https://doi.org/10.1038/hr.2014.152