title: Genetic markers of cholesterol transport and gray matter diffusion: a preliminary study of the CETP I405V polymorphism.
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.
authors.affiliation: Department of Psychological Sciences, University of Missouri-St. Louis, 1 University Blvd., Stadler Hall 442A, St. Louis, MO, 63121, USA. LSalminen@mail.umsl.edu.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Salminen
authors.affiliation: Neuroscience Research Australia, Barker Street Randwick, Sydney, NSW, 2031, Australia.|School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Schofield
authors.affiliation: Neuroscience Research Australia, Barker Street Randwick, Sydney, NSW, 2031, Australia.
authors.forename: Kerrie D
authors.initials: KD
authors.lastname: Pierce
authors.affiliation: Department of Biostatistics and Center for Statistical Sciences, Brown University, Providence, RI, 02912, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Biostatistics and Center for Statistical Sciences, Brown University, Providence, RI, 02912, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Computer Science Department, Brown University, Providence, RI, 02912, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Laidlaw
authors.affiliation: Computer Science Department, Brown University, Providence, RI, 02912, USA.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Cabeen
authors.affiliation: Washington University School of Medicine, Mallinckrodt Institute of Radiology, 510 S. Kingshighway, St. Louis, MO, 63110, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Conturo
authors.affiliation: Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN, 37232, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Lane
authors.affiliation: Missouri Institute of Mental Health, 4633 World Parkway Circle, Berkeley, MO, 63134-3115, USA.
authors.forename: Jodi M
authors.initials: JM
authors.lastname: Heaps
authors.affiliation: Department of Psychological Sciences, University of Missouri-St. Louis, 1 University Blvd., Stadler Hall 442A, St. Louis, MO, 63121, USA.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Bolzenius
authors.affiliation: Department of Psychological Sciences, University of Missouri-St. Louis, 1 University Blvd., Stadler Hall 442A, St. Louis, MO, 63121, USA.
authors.forename: Laurie M
authors.initials: LM
authors.lastname: Baker
authors.affiliation: Department of Psychological Sciences, University of Missouri-St. Louis, 1 University Blvd., Stadler Hall 442A, St. Louis, MO, 63121, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Cooley
authors.affiliation: Missouri Institute of Mental Health, 4633 World Parkway Circle, Berkeley, MO, 63134-3115, USA.
authors.forename: Staci
authors.initials: S
authors.lastname: Scott
authors.affiliation: Department of Psychological Sciences, University of Missouri-St. Louis, 1 University Blvd., Stadler Hall 442A, St. Louis, MO, 63121, USA.
authors.forename: Lee M
authors.initials: LM
authors.lastname: Cagle
authors.affiliation: Department of Psychological Sciences, University of Missouri-St. Louis, 1 University Blvd., Stadler Hall 442A, St. Louis, MO, 63121, USA.|Missouri Institute of Mental Health, 4633 World Parkway Circle, Berkeley, MO, 63134-3115, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Paul
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016880:Anisotropy; D001057:Apolipoproteins E / Q000235:genetics; D001692:Biological Transport / Q000235:genetics*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D066128:Gray Matter / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D015233:Models, Statistical; D011110:Polymorphism, Genetic
chemical_list: D001057:Apolipoproteins E; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D002784:Cholesterol
keywords: APOE; CETP; DTI; Gray matter