title: Association of circadian genes with diurnal blood pressure changes and non-dipper essential hypertension: a genetic association with young-onset hypertension.
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.
authors.affiliation: 1] Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan [2] Heath Care and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan [3] Divison of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Hsin-Bang
authors.initials: HB
authors.lastname: Leu
authors.affiliation: 1] Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan [2] Environment-Omics-Disease Research Center, China Medical University Hospital, Taichung, Taiwan [3] Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Chia-Min
authors.initials: CM
authors.lastname: Chung
authors.affiliation: 1] Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan [2] Divison of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Kuang-Mao
authors.initials: KM
authors.lastname: Chiang
authors.affiliation: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Hsin-Chou
authors.initials: HC
authors.lastname: Yang
authors.affiliation: Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Hung-Yun
authors.initials: HY
authors.lastname: Ho
authors.affiliation: Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Chih-Tai
authors.initials: CT
authors.lastname: Ting
authors.affiliation: Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Sheng-Hsiung
authors.initials: SH
authors.lastname: Sheu
authors.affiliation: National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Tsai
authors.affiliation: National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Jyh-Hong
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Cheng Hsin Rehabilitation Medical Center, Taipei, Taiwan.
authors.forename: Wei-Hsian
authors.initials: WH
authors.lastname: Yin
authors.affiliation: Min Sheng General Hospital, Taoyuan, Taiwan.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Chiu
authors.affiliation: Min Sheng General Hospital, Taoyuan, Taiwan.
authors.forename: Chin-Iuan
authors.initials: CI
authors.lastname: Chen
authors.affiliation: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Cathy Sj
authors.initials: CS
authors.lastname: Fann
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Wen-Harn
authors.initials: WH
authors.lastname: Pan
authors.affiliation: 1] Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan [2] Divison of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan [3] Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001794:Blood Pressure / Q000235:genetics*; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm / Q000235:genetics*; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D056925:Circadian Rhythm Signaling Peptides and Proteins