Salt Loading and Thiazide Intervention Study

Although hypertension can be easily diagnosed and there are many medications available to
treat hypertension, this condition is poorly managed in many patients and is a leading cause
of morbidity and mortality worldwide. Because a newly identified hypertension susceptibility
gene, STK39 (Serine Threonine Kinase 39), plays a central role in kidney sodium transport,
the investigators propose a pharmacogenetics study to examine the relationships between STK39
genotypes and blood pressure responses to salt loading and to thiazide diuretics,
hydrochlorothiazide. In addition, STK39 genotypes may also predict those hypertension
patients more likely to develop thiazide-induced hyperglycemia. The investigators hypothesize
that STK39 genotypes of those single nucleotide polymorphisms (SNPs) that are associated with
baseline systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension
status, will be associated with the outcome of both interventions. Therefore these SNPs can
act as markers and contribute to personalized care for hypertension by identifying patients
most likely to effectively control their blood pressure by adopting salt-reducing diet versus
patients most likely to effectively and safely control their blood pressure by taking
thiazide diuretics.

Inclusion Criteria:

- Old Order Amish

- Age 18 to 65

- Have systolic blood pressure between 120 and 160 and diastolic blood pressure between
80 and 100

Exclusion Criteria:

- History of myocardial infarction, stroke, congestive heart failure, liver disease

- Known cause of secondary hypertension

- Diabetes or Fasting glucose > 100 mg/dL

- Women who are pregnant, on oral contraceptives, or menstruating

- Used hydrochlorothiazide (HCTZ) in the last 8 weeks or known allergy to HCTZ

- Taking non-steroidal anti-inflammatory drugs

- Estimated glomerular filtration rate < 80 mL/m

- Intention to alter dietary habit during the study

- Abuse of alcohol or drug