Genetics of variation in HOMA-IR and cardiovascular risk factors in Mexican-Americans

Insulin resistance is a major biochemical defect underlying the pathogenesis of cardiovascular disease (CVD). Mexican-Americans are known to have an unfavorable cardiovascular profile. Thus, the aim of this study was to investigate the genetic effect on variation in HOMA-IR and to evaluate its genet...

Full description

Saved in:
Bibliographic Details
Published in:Journal of molecular medicine (Berlin, Germany) Germany), 2008-03, Vol.86 (3), p.303-311
Main Authors: Voruganti, V. Saroja, Lopez-Alvarenga, Juan C., Nath, Subrata D., Rainwater, David L., Bauer, Richard, Cole, Shelley A., MacCluer, Jean W., Blangero, John, Comuzzie, Anthony G.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cardiovascular Diseases - ethnology
Cardiovascular Diseases - genetics
Female
General aspects
Genetic Predisposition to Disease
Genetic Variation
Human Genetics
Humans
Insulin Resistance - genetics
Internal Medicine
Lod Score
Male
Medical sciences
Mexican Americans - genetics
Middle Aged
Molecular Medicine
Original Article
Phenotype
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Insulin resistance is a major biochemical defect underlying the pathogenesis of cardiovascular disease (CVD). Mexican-Americans are known to have an unfavorable cardiovascular profile. Thus, the aim of this study was to investigate the genetic effect on variation in HOMA-IR and to evaluate its genetic correlations with other phenotypes related to risk of CVD in Mexican-Americans. The homeostatic model assessment method (HOMA-IR) is one of several approaches that are used to measure insulin resistance and was used here to generate a quantitative phenotype for genetic analysis. For 644 adults who had participated in the San Antonio Family Heart Study (SAFHS), estimates of genetic contribution were computed using a variance components method implemented in SOLAR. Traits that exhibited significant heritabilities were body mass index (BMI) ( h 2 = 0.43), waist circumference ( h 2 = 0.48), systolic blood pressure ( h 2 = 0.30), diastolic blood pressure ( h 2 = 0.21), pulse pressure ( h 2 = 0.32), triglycerides ( h 2 = 0.51), LDL cholesterol ( h 2 = 0.31), HDL cholesterol ( h 2 = 0.24), C-reactive protein ( h 2 = 0.17), and HOMA-IR ( h 2 = 0.33). A genome-wide scan for HOMA-IR revealed significant evidence of linkage on chromosome 12q24 (close to PAH (phenylalanine hydroxylase), LOD = 3.01, p < 0.001). Bivariate analyses demonstrated significant genetic correlations ( p < 0.05) of HOMA-IR with BMI ( ρ G = 0.36), waist circumference ( ρ G = 0.47), pulse pressure ( ρ G = 0.39), and HDL cholesterol ( ρ G = -0.18). Identification of significant linkage for HOMA-IR on chromosome 12q replicates previous family-based studies reporting linkage of phenotypes associated with type 2 diabetes in the same chromosomal region. Significant genetic correlations between HOMA-IR and phenotypes related to CVD risk factors suggest that a common set of gene(s) influence the regulation of these phenotypes.
ISSN:0946-2716
1432-1440
DOI:10.1007/s00109-007-0273-3