Official Title
Effect of the Interaction Between Environmental Factors and Salt-sensitive Genomics on Long-term Blood Pressure in Chinese Population
Brief Title
Longitudinal Follow-up Study in Two Chinese Hypertension Cohorts
Protocol ID
NCT04471389
Lead Sponsor
First Affiliated Hospital Xi'an Jiaotong University
Brief Summary
Essential hypertension is a complex trait that results from interaction between
environmental factors and genetic factors. Salt sensitivity is the genetic susceptibility
of blood pressure to salt, and it is an intermediate genetic phenotype of essential
hypertension. This study aims to investigate the effects of interaction between salt
sensitivity genomics and environmental factors on long-term blood pressure (BP) and
target organ damage based on two established cohorts including "the cohort of Hanzhong
adolescent hypertension study" and "the cohort of Mei county adult salt-sensitive
hypertension study". Firstly, the Hanzhong cohort-based follow-up study is designed to
observe the track of BP from childhood, and to explore the effects of many risk factors
(such as salt-sensitivity, obesity et al) on long-term BP changes and the occurrence of
TODs. In addition, by using DNA samples collected from subjects of "Mei county adult
salt-sensitive hypertension study" in which all participants had completed a chronic salt
loading and potassium intervention trial, investigators attempt to carry out whole-exome
sequencing (WES), whole-genome DNA methylation and transcriptome detection, and analyze
the relationship between salt sensitivity genomics and BP responses to dietary
sodium/potassium intervention, long-term BP change, the risk of target organ damages.
Investigators aim to explore the role of risk factors, including salt sensitivity, in the
development of hypertension, and to illustrate the effects of interaction between salt
sensitivity genomics and environmental factors on hypertension and target organ damage.
This study would enable the investigators to further explore the genetic mechanism of
essential hypertension, to identify new genetic markers for predicting early hypertension
and target organ damage as well as to provide the basis for the prevention, targeted
treatment, and new drugs development of hypertension in the future.
Detailed Description
This study is a longitudinal cohort follow-up study. The main contents include:
(1) Questionnaire design: the questionnaire is designed according to the research
contents and purposes. The standard questionnaires will be used to collect the general
information, dietary habits, lifestyle, medical history, and family history etc. (2)
Anthropometric measurements: blood pressure, pulse, height, body weight, waist and hip
circumference will be acquired by medical practitioners who received professional
training based on World Health Organization (WHO) standards, and passed relevant
examinations. (3) Blood and urine samples collection: morning fasting blood, nocturia,
and 24-hour urine specimen will be collected by medical staffs, and blind tubes will be
set up according to 5% of the total samples. Blood biochemistries including serum total
cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, fasting glucose, creatinine
and hsCRP can be measured using automatic biochemical analyzer. The sodium and potassium
concentrations in the urine will be measured by flame photometry. The total sodium and
potassium excretions in urine in 24h were calculated by multiplying the concentration and
24-h volume of urine. (4) Auxiliary examinations: Auxiliary examinations including
carotid intima-media thickness, endothelium-dependent vasodilation (FMD), measurements of
brachial-ankle pulse wave velocity (baPWV) and electrocardiographic parameters. The
measurement will be done in hospitals by medical practitioners who received professional
trainings and passed relevant examinations. (5) Whole-exome sequencing: Genomic DNA will
be isolated from blood samples and subjected to exome capture, followed by
next-generation sequencing on the Roche NimbleGen system. (6) Whole-genome DNA
methylation analysis: levels of DNA methylation will be quantified using the Illumina
Infinium HumanMethylation450K Beadchip array (HM450K). (7) Transcriptome sequencing: cDNA
libraries will be sequenced via the Illumina HiSeqTM 2500 platform. (8) Data processing
and statistics: investigators should input the data to the database, and utilize software
such as Access, SPSS, STATA, CASAVA, MutSigCV, and Genome MuSic to analyze. (9) Quality
control: ① Questionnaire is strictly designed and amended by epidemiologists and clinical
experts. ② A standardized "Investigator Handbook" will be stipulated according to the
guidelines. ③ Staff members are required to do a rigorous training and pass the exam. ④
The investigation process will be strictly supervised by the principal investigator. ⑤
Data entry uses the parallel double-entry method. ⑥ During laboratory testing, blank
control and blind detection are applied to ensure the quality. ⑦ Data analysis is
performed by 2-3 postgraduates, inconsistent data need to be double-checked.
Enrollment Count
5,611 participants
Eligibility Criteria
Inclusion Criteria:
1. Hanzhong cohort of Adolescent Hypertension Study:
• adolescents aged 6-15 years old in over 20 schools of three towns (Qili, Laojun
and Shayan) in Hanzhong, Shaanxi, China.
2. Mei county cohort of adult salt-sensitive hypertension study:
- Han individuals in rural northern China
- adults aged 18-60 years
- individuals who had a mean systolic BP (SBP) between 130-160 mmHg and/or a
diastolic BP (DBP) between 85-100 mmHg and no use of antihypertensive
medications were identified as the proband
- the probands'parents, siblings, spouses, and offspring were recruited for the
study.
Exclusion Criteria:
- Secondary hypertension
- a history of severe cardiovascular disease
- chronic kidney disease or liver disease
- unable to complete the examination
- unable/refuse to sign the informed consent form
Filters
Hypertension
UNKNOWN
ADULT
OLDER_ADULT