title: Genetics of variation in HOMA-IR and cardiovascular risk factors in Mexican-Americans.
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 (rho (G) = 0.36), waist circumference (rho (G) = 0.47), pulse pressure (rho (G) = 0.39), and HDL cholesterol (rho (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.
authors.affiliation: Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA. svorugan@sfbrgenetics.org
authors.forename: V Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.forename: Juan C
authors.initials: JC
authors.lastname: Lopez-Alvarenga
authors.forename: Subrata D
authors.initials: SD
authors.lastname: Nath
authors.forename: David L
authors.initials: DL
authors.lastname: Rainwater
authors.forename: Richard
authors.initials: R
authors.lastname: Bauer
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.forename: Jean W
authors.initials: JW
authors.lastname: Maccluer
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
mesh_terms: D002318:Cardiovascular Diseases / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008126:Lod Score; D008297:Male; D017058:Mexican Americans / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype