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

V. Saroja Voruganti, Juan C. Lopez-Alvarenga, Subrata D. Nath, David L Rainwater, Richard L Bauer, Shelley A. Cole, Jean W. MacCluer, John C Blangero, Anthony G Comuzzie

Resultado de la investigación: Articlerevisión exhaustiva

27 Citas (Scopus)


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.

Idioma originalEnglish (US)
Páginas (desde-hasta)303-311
Número de páginas9
PublicaciónJournal of Molecular Medicine
EstadoPublished - mar 2008

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)


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