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Genetic variants associated with VLDL, LDL and HDL particle size differ with race/ethnicity

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Abstract

Specific constellations of lipoprotein particle features, reflected as differences in mean lipoprotein particle diameters, are associated with risk of insulin resistance (IR) and cardiovascular disease (CVD). The associations of lipid profiles with disease risk differ by race/ethnicity, the reason for this is not clear. We aimed to examine whether there were additional genetic differences between racial/ethnic groups on lipoprotein profile. Genotypes were assessed using the Affymetrix 6.0 array in 817 related Caucasian participants of the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). Association analysis was conducted on fasting mean particle diameters using linear models, adjusted for age, sex and study center as fixed effects, and pedigree as a random effect. Replication of associations reaching P < 1.97 × 10−05 (the level at which we achieved at least 80 % power to replicate SNP-phenotype associations) was conducted in the Caucasian population of the Multi-Ethnic Study of Atherosclerosis (MESA; N = 2,430). Variants which replicated across both Caucasian populations were subsequently tested for association in the African-American (N = 1,594), Chinese (N = 758), and Hispanic (N = 1,422) populations of MESA. Variants in the APOB gene region were significantly associated with mean VLDL diameter in GOLDN, and in the Caucasian and Hispanic populations of MESA, while variation in the hepatic lipase (LIPC) gene was associated with mean HDL diameter in both Caucasians populations only. Our findings suggest that the genetic underpinnings of mean lipoprotein diameter differ by race/ethnicity. As lipoprotein diameters are modifiable, this may lead new strategies to modify lipoprotein profiles during the reduction of IR that are sensitive to race/ethnicity.

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Acknowledgments

We are grateful to the staff of the GOLDN study for the assistance in data collection and management. The authors thank the participants of the MESA study, the Coordinating Center, MESA investigators, and study staff for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. GOLDN is funded by National Heart, Lung, and Blood Institute [grant number U01HL072524-04]. MESA and the MESA SHARe project are conducted and supported by contracts N01-HC-95159 through N01-HC-95169 and RR-024156 from the National Heart, Lung, and Blood Institute. Funding for MESA SHARe genotyping was provided by National Heart, Lung, and Blood Institute [Contract N02‐HL‐6‐4278]. MESA Family is conducted and supported in collaboration with MESA investigators; support is provided by National Heart, Lung, and Blood Institute grants and contracts [grant numbers R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL071258, R01HL071259].

Conflict of interest

All authors declare that they have no conflicts of interests.

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Authors and Affiliations

  1. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA

    Alexis C. Frazier-Wood, Stella Aslibekyan & Donna K. Arnett

  2. Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL, USA

    Hemant K. Tiwari

  3. Division of Epidemiology, Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, TX, USA

    Alexis C. Frazier-Wood

  4. Division of Biostatistics and Epidemiology, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA

    Ani Manichaikul

  5. Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA

    Ani Manichaikul, Stephen S. Rich & Michèle M. Sale

  6. Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA

    Ingrid B. Borecki

  7. Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA

    David C. Goff

  8. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA

    Paul N. Hopkins

  9. Nutrition and Genomics Laboratory, Jean Mayer-US Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA

    Chao-Qiang Lai & Jose M. Ordovas

  10. The Department of Epidemiology and Population Genetics, Centro Nacional Investigación Cardiovasculares (CNIC), Madrid, Spain

    Jose M. Ordovas

  11. IMDEA Food, Madrid, Spain

    Jose M. Ordovas

  12. Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Wendy S. Post

  13. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Wendy S. Post

  14. Cardiovascular Health Research Unit, Department of Medicine and Epidemiology, University of Washington, Seattle, WA, USA

    David Siscovick

  15. Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA

    Robert J. Straka

  16. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

    Michael Y. Tsai

  17. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Jerome I. Rotter

  18. Department of Medicine, University of Virginia, Charlottesville, VA, USA

    Michèle M. Sale

  19. Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA

    Michèle M. Sale

Authors
  1. Alexis C. Frazier-Wood
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  2. Ani Manichaikul
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  3. Stella Aslibekyan
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  5. David C. Goff
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  7. Chao-Qiang Lai
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  8. Jose M. Ordovas
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  14. Hemant K. Tiwari
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Correspondence to Alexis C. Frazier-Wood.

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Frazier-Wood, A.C., Manichaikul, A., Aslibekyan, S. et al. Genetic variants associated with VLDL, LDL and HDL particle size differ with race/ethnicity. Hum Genet 132, 405–413 (2013). https://doi.org/10.1007/s00439-012-1256-1

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