Journal of Molecular Medicine

, Volume 86, Issue 3, pp 303–311 | Cite as

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 Bauer
  • Shelley A. Cole
  • Jean W. MacCluer
  • John Blangero
  • Anthony G. Comuzzie
Original Article


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) (h2 = 0.43), waist circumference (h2 = 0.48), systolic blood pressure (h2 = 0.30), diastolic blood pressure (h2 = 0.21), pulse pressure (h2 = 0.32), triglycerides (h2 = 0.51), LDL cholesterol (h2 = 0.31), HDL cholesterol (h2 = 0.24), C-reactive protein (h2 = 0.17), and HOMA-IR (h2 = 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 (ρG = 0.36), waist circumference (ρG = 0.47), pulse pressure (ρG = 0.39), and HDL cholesterol (ρG = -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.


Insulin resistance Variance component approach Genetic correlations 



We wish to thank all participants of the San Antonio Family Heart Study for their cooperation and generous participation. This study was supported by PO1 HL4522 from NHLBI and MH59490 from NIH.


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • V. Saroja Voruganti
    • 1
    • 3
  • Juan C. Lopez-Alvarenga
    • 1
  • Subrata D. Nath
    • 2
  • David L. Rainwater
    • 1
  • Richard Bauer
    • 2
  • Shelley A. Cole
    • 1
  • Jean W. MacCluer
    • 1
  • John Blangero
    • 1
  • Anthony G. Comuzzie
    • 1
  1. 1.Southwest Foundation for Biomedical ResearchSan AntonioUSA
  2. 2.University of Texas Health Science Center at San AntonioSan AntonioUSA
  3. 3.Department of GeneticsSouthwest Foundation for Biomedical ResearchSan AntonioUSA

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