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

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)303-311
Number of pages9
JournalJournal of Molecular Medicine
Volume86
Issue number3
DOIs
StatePublished - Mar 1 2008

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Keywords

  • Genetic correlations
  • Insulin resistance
  • Variance component approach

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

Cite this

Voruganti, V. S., Lopez-Alvarenga, J. C., Nath, S. D., Rainwater, D. L., Bauer, R., Cole, S. A., MacCluer, J. W., Blangero, J., & Comuzzie, A. G. (2008). Genetics of variation in HOMA-IR and cardiovascular risk factors in Mexican-Americans. Journal of Molecular Medicine, 86(3), 303-311. https://doi.org/10.1007/s00109-007-0273-3