The Hypertension-Insulin Resistance Family Study (HTN-IR)

The HTN-IR Study, funded by NHLBI, was designed to explore genetic contributions to hypertension and glucose homeostasis traits among Hispanics using a family-based design. The baseline examination of the cohort included the euglycemic hyperinsulinemic clamp test from which the two key phenotypes were obtained: insulin sensitivity (M) and metabolic clearance rate of insulin (MCRI). Genome-wide genotyping was obtained under separate funding by NIDDK as a part of the GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium.

• Study Design:
  • Family/Twin/Trios
• Study Type:
  • Cohort
  • Family
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 765
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• BioSample
• MeSH
• Gene
• PMC

HTN-IR Inclusion:

• Family: A family was eligible for recruitment if the proband had essential hypertension, at least two adult offspring were available for detailed phenotyping, and DNA could be obtained from at least four members of the nuclear family (i.e., any combination of proband, his/her spouse, and their offspring. When available, spouses in the offspring generation were also studied to act as environmental controls.
• Probands: age 18-65, hypertension (sitting BP≥140/90 mm Hg off medication), met family requirements above, and able to give informed consent.
• Spouses/Offspring: ≥18 years, parent or spouse with essential hypertension diagnosed before age 65: able to give informed consent.

HTN-IR Exclusion and Limited Study Criteria:
Subjects only had baseline bloods drawn, including for DNA if they had the following (includes all subjects):

• Evidence of secondary forms of hypertension; myocardial infarction, stroke, or cardiac revascularization/angioplasty within 6 months;
  
• Blood pressure >200/115 mm Hg or hypertensive retinopathy > grade II;
• Symptoms or exam evidence of congestive heart failure or known left ventricular ejection fraction <35%;
• Current pregnancy;
• Significant medical illness;
• Serum potassium <3.5 or >5.5 mEq/l off medications;
• Serum albumin <2.5 g/dl;
• Serum creatinine >2.0 mg/dl;
• Serum AST or ALT >3x normal;
• Hematocrit <33%;
• Proteinuria >1+ confirmed with 24 hour excretion >500 mg;
• Fasting glucose >140 mg/dl or 2-hour post-load (75 g dextrose) glucose >200 mg/dl.

The HTN-IR Study was established in 1996 by the National Heart, Lung and Blood Institute (NHLBI). The HTN-IR Study cohort of 936 participants (representing 169 Hispanic families) was initially recruited in 1996-2001 from Los Angeles, CA. 836 participants were genotyped and 71 of them were removed during quality control. Only 765 genotyped samples were left for HTN-IR.

• Primary Phenotype: Hypertension
• Insulin Resistance

• NAT2
• CAV1
• CAPN10
• KDM1A

• Principal Investigator
  • Jerome I. Rotter, MD. Los Angeles BioMedical Research Institute at Harbor-UCLA, Los Angeles, CA, USA.
• Funding Source
  • National Heart, Lung, and Blood Institute grant (RO1 HL04788705). National Institutes of Health, Bethesda, MD, USA.
  • National Institute of Diabetes and Digestive and Kidney Diseases GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium grant (R01 DK085175). National Institutes of Health, Bethesda, MD, USA.