title: APOL1 associations with nephropathy, atherosclerosis, and all-cause mortality in African Americans with type 2 diabetes.
abstract: Albuminuria and reduced estimated glomerular filtration rate (eGFR) associate with two apolipoprotein L1 gene (APOL1) variants in nondiabetic African Americans (AAs). Whether APOL1 associates with subclinical atherosclerosis and survival remains unclear. To determine this, 717 African American-Diabetes Heart Study participants underwent computed tomography to determine coronary artery-, carotid artery-, and aorta-calcified atherosclerotic plaque mass scores in addition to the urine albumin:creatinine ratio (UACR), eGFR, and C-reactive protein (CRP). Associations between mass scores and APOL1 were assessed adjusting for age, gender, African ancestry, body mass index (BMI), hemoglobin A1c, smoking, hypertension, use of statins and angiotensin-converting enzyme inhibitors, albuminuria, and eGFR. Participants were 58.9% female with mean age 56.5 years, eGFR 89.5 ml/min per 1.73 m(2), UACR 169.6 mg/g, and coronary artery-, carotid artery-, and aorta-calcified plaque mass scores of 610, 171, and 5378, respectively. In fully adjusted models, APOL1 risk variants were significantly associated with lower levels of carotid artery-calcified plaque (β=-0.42, s.e. 0.18; dominant model) and marginally lower coronary artery plaque (β=-0.36, s.e. 0.21; dominant model), but not with aorta-calcified plaque, CRP, UACR, or eGFR. By the end of a mean follow-up of 5.0 years, 89 participants had died. APOL1 nephropathy risk variants were significantly associated with improved survival (hazard ratio 0.67 for one copy; 0.44 for two copies). Thus, APOL1 nephropathy variants associate with lower levels of subclinical atherosclerosis and reduced risk of death in AAs with type 2 diabetes mellitus.
authors: 1] Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [2] Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [3] Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [4] Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Barry I
authors: BI
authors: Freedman
authors: 1] Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [2] Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [3] Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [4] Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Carl D
authors: CD
authors: Langefeld
authors: 1] Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [2] Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Lingyi
authors: L
authors: Lu
authors: 1] Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [2] Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [3] Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [4] Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Nicholette D
authors: ND
authors: Palmer
authors: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: S Carrie
authors: SC
authors: Smith
authors: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Benjamin M
authors: BM
authors: Bagwell
authors: Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Pamela J
authors: PJ
authors: Hicks
authors: 1] Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [2] Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [3] Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Jianzhao
authors: J
authors: Xu
authors: Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Lynne E
authors: LE
authors: Wagenknecht
authors: 1] Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [2] Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Laura M
authors: LM
authors: Raffield
authors: Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Thomas C
authors: TC
authors: Register
authors: Department of Radiology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: J Jeffrey
authors: JJ
authors: Carr
authors: 1] Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [2] Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [3] Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Donald W
authors: DW
authors: Bowden
authors: 1] Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [2] Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [3] Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA [4] Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Jasmin
authors: J
authors: Divers
mesh_terms: D001741:Black or African American; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D050197:Atherosclerosis / Q000150:complications / Q000235:genetics*; D002423:Cause of Death; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000401:mortality*; D003928:Diabetic Nephropathies / Q000150:complications / Q000235:genetics* / Q000401:mortality*; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL