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 m2, 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 440-449 |
| Number of pages | 10 |
| Journal | Kidney International |
| Volume | 90 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 1 2016 |
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Keywords
- African Americans
- APOL1
- brain
- cognition
- hypertension
- magnetic resonance imaging
- type 2 diabetes mellitus
ASJC Scopus subject areas
- Medicine(all)
- Nephrology
Cite this
APOL1 renal-risk variants associate with reduced cerebral white matter lesion volume and increased gray matter volume. / African American–Diabetes Heart Study MIND (AA-DHS MIND) and Systolic Blood Pressure Intervention Trial (SPRINT) Research Groups.
In: Kidney International, Vol. 90, No. 2, 01.08.2016, p. 440-449.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - APOL1 renal-risk variants associate with reduced cerebral white matter lesion volume and increased gray matter volume
AU - African American–Diabetes Heart Study MIND (AA-DHS MIND) and Systolic Blood Pressure Intervention Trial (SPRINT) Research Groups
AU - Freedman, Barry I.
AU - Gadegbeku, Crystal A.
AU - Bryan, R. Nick
AU - Palmer, Nicholette D.
AU - Hicks, Pamela J.
AU - Ma, Lijun
AU - Rocco, Michael V.
AU - Smith, S. Carrie
AU - Xu, Jianzhao
AU - Whitlow, Christopher T.
AU - Wagner, Benjamin C.
AU - Langefeld, Carl D.
AU - Hawfield, Amret T.
AU - Bates, Jeffrey T.
AU - Lerner, Alan J.
AU - Raj, Dominic S.
AU - Sadaghiani, Mohammad S.
AU - Toto, Robert D
AU - Wright, Jackson T.
AU - Bowden, Donald W.
AU - Williamson, Jeff D.
AU - Sink, Kaycee M.
AU - Maldjian, Joseph A
AU - Pajewski, Nicholas M.
AU - Divers, Jasmin
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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 m2, 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.
AB - 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 m2, 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.
KW - African Americans
KW - APOL1
KW - brain
KW - cognition
KW - hypertension
KW - magnetic resonance imaging
KW - type 2 diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=84992520139&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992520139&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2016.04.027
DO - 10.1016/j.kint.2016.04.027
M3 - Article
C2 - 27342958
AN - SCOPUS:84992520139
VL - 90
SP - 440
EP - 449
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 2
ER -