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Kidney Int. 2016 Aug;90(2):440-449. doi: 10.1016/j.kint.2016.04.027. Epub 2016 Jun 22.

APOL1 renal-risk variants associate with reduced cerebral white matter lesion volume and increased gray matter volume.

Author information

1
Department of Internal Medicine, Section on Nephrology; Wake Forest School of Medicine, Winston-Salem, NC.
2
Centers for Diabetes Research and Genomics and Personalized Medicine Research; Wake Forest School of Medicine, Winston-Salem, NC.
3
Department of Medicine, Temple University School of Medicine, Philadelphia, PA.
4
Department of Radiology, University of Pennsylvania, Philadelphia, PA.
5
Department of Biochemistry; Wake Forest School of Medicine, Winston-Salem, NC.
6
Department of Radiologic Sciences, Advanced Neuroscience Imaging Research (ANSIR) Laboratory; Wake Forest School of Medicine, Winston-Salem, NC.
7
Division of Public Health Sciences, Department of Biostatistical Sciences; Wake Forest School of Medicine, Winston-Salem, NC.
8
Michael E. DeBakey Veterans Administration Medical Center and Baylor College of Medicine, Houston, TX.
9
Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH.
10
Department of Medicine, George Washington University, Washington, DC.
11
Department of Internal Medicine, University of Texas, Southwestern Medical Center, Dallas, TX.
12
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH.
13
Department of Internal Medicine, Section on Gerontology and Geriatric Medicine; Wake Forest School of Medicine, Winston-Salem, NC.
14
Department of Radiology, Advanced Neuroscience Imaging Research (ANSIR) Laboratory; University of Texas Southwestern Medical Center, Dallas, TX.
#
Contributed equally

Abstract

To assess apolipoprotein L1 gene (APOL1) renal-risk-variant effects on the brain, magnetic resonance imaging (MRI)-based cerebral volumes and cognitive function were assessed in 517 African American-Diabetes Heart Study (AA-DHS) Memory IN Diabetes (MIND) and 2568 hypertensive African American Systolic Blood Pressure Intervention Trial (SPRINT) participants without diabetes. Within these cohorts, 483 and 197 had cerebral MRI, respectively. AA-DHS participants were characterized as follows: 60.9% female, mean age of 58.6 years, diabetes duration 13.1 years, estimated glomerular filtration rate of 88.2 ml/min/1.73 m(2), and a median spot urine albumin to creatinine ratio of 10.0 mg/g. In additive genetic models adjusting for age, sex, ancestry, scanner, intracranial volume, body mass index, hemoglobin A1c, statins, nephropathy, smoking, hypertension, and cardiovascular disease, APOL1 renal-risk-variants were positively associated with gray matter volume (β = 3.4 × 10(-3)) and negatively associated with white matter lesion volume (β = -0.303) (an indicator of cerebral small vessel disease) and cerebrospinal fluid volume (β= -30707) (all significant), but not with white matter volume or cognitive function. Significant associations corresponding to adjusted effect sizes (β/SE) were observed with gray matter volume (0.16) and white matter lesion volume (-0.208), but not with cerebrospinal fluid volume (-0.251). Meta-analysis results with SPRINT Memory and Cognition in Decreased Hypertension (MIND) participants who had cerebral MRI were confirmatory. Thus, APOL1 renal-risk-variants are associated with larger gray matter volume and lower white matter lesion volume suggesting lower intracranial small vessel disease.

KEYWORDS:

APOL1; African Americans; brain; cognition; hypertension; magnetic resonance imaging; type 2 diabetes mellitus

PMID:
27342958
PMCID:
PMC4946987
DOI:
10.1016/j.kint.2016.04.027
[Indexed for MEDLINE]
Free PMC Article

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