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Genetic markers of cholesterol transport and gray matter diffusion: a preliminary study of the CETP I405V polymorphism

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

Variations of the cholesteryl ester transfer protein polymorphism (CETP I405V/rs5882) have been associated with an increased risk for neurodegeneration, particularly when examined in conjunction with the epsilon 4 isoform of apolipoprotein E (ApoE4). Despite these identified relationships, the impact of I405V on gray matter microstructure remains unknown. The present study examined the impact of the CETP I405V polymorphism on gray matter integrity among 52 healthy adults between ages 51 and 85. Gray matter was measured bilaterally using diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Participants were grouped according to a dominant statistical model (II genotype vs. IV/VV genotypes) and secondary analyses were completed to examine the interactive effects of CETP and ApoE4 on DTI metrics. Compared to individuals with the IV/VV genotypes, II homozygotes demonstrated significantly higher MD in bilateral temporal, parietal, and occipital gray matter. Secondary analyses revealed higher FA and AD in the left temporal lobe of IV/VV genotypes with an ApoE4 allele. Our results provide preliminary evidence that CETP II homozygosity is a predisposing risk factor for gray matter abnormalities in posterior brain regions in healthy older adults, independent of an ApoE4 allele.

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Acknowledgments

Study Funding: Supported by the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) grants R01 NS052470 and R01 NS039538, and NIH/National Institute of Mental Health (NIMH) grant R21 MH090494 and the Australian National Health and Medical Research Council (NHMRC) grant 1037196. DNA extractions were performed by Genetic Repositories Australia, an Enabling Facility, which is supported by NHMRC Grant 401184. Recruitment database searches were supported in part by NIH/National Center for Research Resources (NCRR) grant UL1 TR000448. Statistical procedures were supported by the NIH grants P01AA019072, P20GM103645, P30AI042853, R01NS052470, and S10OD016366.

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Authors and Affiliations

  1. Department of Psychological Sciences, University of Missouri-St. Louis, 1 University Blvd., Stadler Hall 442A, St. Louis, MO, 63121, USA

    Lauren E. Salminen, Jacob D. Bolzenius, Laurie M. Baker, Sarah A. Cooley, Lee M. Cagle & Robert H. Paul

  2. Neuroscience Research Australia, Barker Street Randwick, Sydney, NSW, 2031, Australia

    Peter R. Schofield & Kerrie D. Pierce

  3. School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia

    Peter R. Schofield

  4. Department of Biostatistics and Center for Statistical Sciences, Brown University, Providence, RI, 02912, USA

    Xi Luo & Yi Zhao

  5. Computer Science Department, Brown University, Providence, RI, 02912, USA

    David H. Laidlaw & Ryan P. Cabeen

  6. Washington University School of Medicine, Mallinckrodt Institute of Radiology, 510 S. Kingshighway, St. Louis, MO, 63110, USA

    Thomas E. Conturo

  7. Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN, 37232, USA

    Elizabeth M. Lane

  8. Missouri Institute of Mental Health, 4633 World Parkway Circle, Berkeley, MO, 63134-3115, USA

    Jodi M. Heaps, Staci Scott & Robert H. Paul

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  1. Lauren E. Salminen
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Salminen, L.E., Schofield, P.R., Pierce, K.D. et al. Genetic markers of cholesterol transport and gray matter diffusion: a preliminary study of the CETP I405V polymorphism. J Neural Transm 122, 1581–1592 (2015). https://doi.org/10.1007/s00702-015-1434-0

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