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

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 (? = 3.4 × 10(-3)) and negatively associated with white matter lesion volume (? = -0.303) (an indicator of cerebral small vessel disease) and cerebrospinal fluid volume (?= -30707) (all significant), but not with white matter volume or cognitive function. Significant associations corresponding to adjusted effect sizes (?/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.

SUBMITTER: Freedman BI

PROVIDER: S-EPMC4946987 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Freedman Barry I BI Gadegbeku Crystal A CA Bryan R Nick RN Palmer Nicholette D ND Hicks Pamela J PJ Ma Lijun L Rocco Michael V MV Smith S Carrie SC Xu Jianzhao J Whitlow Christopher T CT Wagner Benjamin C BC Langefeld Carl D CD Hawfield Amret T AT Bates Jeffrey T JT Lerner Alan J AJ Raj Dominic S DS Sadaghiani Mohammad S MS Toto Robert D RD Wright Jackson T JT Bowden Donald W DW Williamson Jeff D JD Sink Kaycee M KM Maldjian Joseph A JA Pajewski Nicholas M NM Divers Jasmin J

Kidney international 20160622 2

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% ...[more]

PMID: 27342958

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Project description:Background and purposeWM lesion segmentation is often performed with the use of subjective rating scales because manual methods are laborious and tedious; however, automated methods are now available. We compared the performance of total lesion volume grading computed by use of an automated WM lesion segmentation algorithm with that of subjective rating scales and expert manual segmentation in a cohort of subjects with type 2 diabetes.Materials and methodsStructural T1 and FLAIR MR imaging data from 50 subjects with diabetes (age, 67.7 ± 7.2 years) and 50 nondiabetic sibling pairs (age, 67.5 ± 9.4 years) were evaluated in an institutional review board-approved study. WM lesion segmentation maps and total lesion volume were generated for each subject by means of the Statistical Parametric Mapping (SPM8) Lesion Segmentation Toolbox. Subjective WM lesion grade was determined by means of a 0-9 rating scale by 2 readers. Ground-truth total lesion volume was determined by means of manual segmentation by experienced readers. Correlation analyses compared manual segmentation total lesion volume with automated and subjective evaluation methods.ResultsCorrelation between average lesion segmentation and ground-truth total lesion volume was 0.84. Maximum correlation between the Lesion Segmentation Toolbox and ground-truth total lesion volume (ρ = 0.87) occurred at the segmentation threshold of k = 0.25, whereas maximum correlation between subjective lesion segmentation and the Lesion Segmentation Toolbox (ρ = 0.73) occurred at k = 0.15. The difference between the 2 correlation estimates with ground-truth was not statistically significant. The lower segmentation threshold (0.15 versus 0.25) suggests that subjective raters overestimate WM lesion burden.ConclusionsWe validate the Lesion Segmentation Toolbox for determining total lesion volume in diabetes-enriched populations and compare it with a common subjective WM lesion rating scale. The Lesion Segmentation Toolbox is a readily available substitute for subjective WM lesion scoring in studies of diabetes and other populations with changes of leukoaraiosis.

Dataset Information

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

Publications

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

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