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J Clin Endocrinol Metab. 2011 Aug;96(8):E1288-92. doi: 10.1210/jc.2010-2738. Epub 2011 May 25.

Variants of the caveolin-1 gene: a translational investigation linking insulin resistance and hypertension.

Author information

1
Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

Abstract

CONTEXT:

The co-occurrence of insulin resistance (IR) and hypertension is a heritable condition leading to cardiovascular complications. Caveolin-1 (CAV1), a gene previously associated with metabolic dysfunction in animal and cellular models, may be a marker for these conditions in humans.

OBJECTIVE:

The objective of the study was to examine the relationship between CAV1 variants and IR in two hypertensive cohorts and to corroborate the findings in a CAV1 knockout mouse.

DESIGN, SETTING, AND PARTICIPANTS:

A candidate gene association study was conducted in two hypertensive cohorts: 1) Caucasian and 2) Hispanic. Multivariate associations between individual variants and insulin-resistant phenotypes were analyzed, accounting for age, gender, body mass index, and sibling relatedness. Intraperitoneal glucose tolerance tests were conducted in wild-type and CAV1 knockout mice.

RESULTS:

In the Caucasian hypertensive cohort, minor allele carriers of two CAV1 single-nucleotide polymorphisms (rs926198, rs3807989) had significantly higher fasting insulin levels (P = 0.005, P = 0.007), increased homeostatic assessment model for insulin resistance (HOMA-IR) (P =0.005, P = 0.008), and decreased M value during hyperinsulinemic, euglycemic clamp procedure (P = 0.004, P = 0.05) than major allele homozygotes. Findings were replicated in the Hispanic hypertensive cohort cohort for fasting insulin levels (P = 0.005, P = 0.02) and HOMA-IR (P = 0.008 and P = 0.02). Meta-analysis demonstrated significant associations of both single-nucleotide polymorphisms with fasting insulin levels (P = 0.00008, P = 0.0004) and HOMA-IR (P = 0.0001, P = 0.0004). As compared with wild type, CAV1 knockout mice displayed higher blood pressure levels and higher fasting glucose, insulin, and HOMA-IR levels and an exaggerated glycemic response to a glucose challenge.

CONCLUSION:

Variations in the CAV1 gene are associated with IR and hypertension. CAV1 gene polymorphisms may be a biomarker for IR and hypertension, enabling earlier detection and improved treatment strategies.

PMID:
21613355
PMCID:
PMC3146791
DOI:
10.1210/jc.2010-2738
[Indexed for MEDLINE]
Free PMC Article

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