Udeme E Ekrikpo1, Khuthala Mnika2, Emmanuel E Effa3, Samuel O Ajayi4, Chimezie Okwuonu5, Bala Waziri6, Aminu Bello7, Collet Dandara2, Andre P Kengne8, Ambroise Wonkam9, Ikechi Okpechi10. 1. Department of Medicine, University of Uyo, Uyo, Nigeria; Kidney & Hypertension Research Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa. 2. Division of Human Genetics, University of Cape Town, Cape Town, South Africa. 3. Department of Medicine, University of Calabar, Calabar, Nigeria. 4. Department of Medicine, University of Ibadan, Ibadan, Nigeria. 5. Department of Medicine, Federal Medical Centre, Umuahia, Nigeria. 6. Department of Medicine, IBB Specialist Hospital, Minna, Nigeria. 7. Department of Medicine, University of Alberta, Edmonton, Canada. 8. Non-communicable Disease Research Unit, Medical Research Council, Cape Town, South Africa. 9. Division of Human Genetics, University of Cape Town, Cape Town, South Africa. Electronic address: ambroise.wonkam@uct.ac.za. 10. Kidney & Hypertension Research Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa. Electronic address: ikechi.okpechi@uct.ac.za.
Abstract
RATIONALE & OBJECTIVE: Recent studies in the human immunodeficiency virus (HIV)-infected population have suggested that there are genetic predispositions to the development of chronic kidney disease (CKD) in this context. We investigated the association of genetic polymorphisms of the genes encoding apolipoprotein L1 (APOL1), transforming growth factor β1 (TGF-β1; a profibrotic cytokine), and heme oxygenase 1 (HMOX1) with prevalent CKD among adults with and without HIV infection. STUDY DESIGN: Case-control study. SETTING & PARTICIPANTS: West African adults including 217 HIV-infected patients with CKD (HIV+/CKD+ group), 595 HIV-infected patients without CKD (HIV+/CKD- group), 269 with CKD and no HIV infection (HIV-/CKD+ group), and 114 with neither CKD nor HIV (HIV-/CKD- group). EXPOSURE: The genetic polymorphisms with reference single-nucleotide polymorphism (rs) identification numbers rs1800469 (TGF-β1), rs1800470 (TGF-β1), rs121918282 (TGF-β1); rs60910145 (APOL1 G1 risk allele), rs73885319 (APOL1 G1 risk allele), rs71785313 (APOL1 G2 risk allele), and rs743811 (HMOX1); HIV. OUTCOME: CKD. ANALYTICAL APPROACH: Single-nucleotide polymorphism (SNP) genotyping of rs1800469 (TGF-β1), rs1800470 (TGF-β1), rs121918282 (TGF-β1); rs60910145 (APOL1), rs73885319 (APOL1), rs71785313 (APOL1), and rs743811 (HMOX1) was performed. Hardy-Weinberg equilibrium was evaluated for all SNPs, and minor allele frequencies were reported. A case-control analysis was performed, and multivariable logistic regression was used to control for potential confounders. RESULTS: Minor allele frequencies for TGF-β1 (rs1800469, rs1800470, and rs1800471), APOL1 (rs60910145, rs73885319, and rs71785313), and HMOX1 (rs743811) were 0.25, 0.46, 0.46, 0.44, 0.45, 0.17, and 0.14, respectively. Among HIV-positive individuals, only TGF-β1 rs1800470 (GG vs AA), APOL1 (in the recessive model), and hypertension were associated with prevalent CKD (adjusted ORs of 0.44 [95% CI, 0.20-0.97], 2.54 [95% CI, 1.44-4.51], and 2.17 [95% CI, 1.35-3.48], respectively). No SNP polymorphisms were associated with prevalent CKD among HIV-negative individuals. LIMITATIONS: The lack of histopathology data for proper categorization of the type of HIV-related nephropathy. CONCLUSIONS: APOL1 polymorphisms were highly prevalent in this population and among adult patients infected with HIV and were associated with increased CKD risk. The TGF-β1 (rs1800470) polymorphism was associated with reduced risk, and HMOX1 polymorphisms were unassociated with CKD.
RATIONALE & OBJECTIVE: Recent studies in the human immunodeficiency virus (HIV)-infected population have suggested that there are genetic predispositions to the development of chronic kidney disease (CKD) in this context. We investigated the association of genetic polymorphisms of the genes encoding apolipoprotein L1 (APOL1), transforming growth factor β1 (TGF-β1; a profibrotic cytokine), and heme oxygenase 1 (HMOX1) with prevalent CKD among adults with and without HIV infection. STUDY DESIGN: Case-control study. SETTING & PARTICIPANTS: West African adults including 217 HIV-infectedpatients with CKD (HIV+/CKD+ group), 595 HIV-infectedpatients without CKD (HIV+/CKD- group), 269 with CKD and no HIV infection (HIV-/CKD+ group), and 114 with neither CKD nor HIV (HIV-/CKD- group). EXPOSURE: The genetic polymorphisms with reference single-nucleotide polymorphism (rs) identification numbers rs1800469 (TGF-β1), rs1800470 (TGF-β1), rs121918282 (TGF-β1); rs60910145 (APOL1 G1 risk allele), rs73885319 (APOL1 G1 risk allele), rs71785313 (APOL1 G2 risk allele), and rs743811 (HMOX1); HIV. OUTCOME: CKD. ANALYTICAL APPROACH: Single-nucleotide polymorphism (SNP) genotyping of rs1800469 (TGF-β1), rs1800470 (TGF-β1), rs121918282 (TGF-β1); rs60910145 (APOL1), rs73885319 (APOL1), rs71785313 (APOL1), and rs743811 (HMOX1) was performed. Hardy-Weinberg equilibrium was evaluated for all SNPs, and minor allele frequencies were reported. A case-control analysis was performed, and multivariable logistic regression was used to control for potential confounders. RESULTS: Minor allele frequencies for TGF-β1 (rs1800469, rs1800470, and rs1800471), APOL1 (rs60910145, rs73885319, and rs71785313), and HMOX1 (rs743811) were 0.25, 0.46, 0.46, 0.44, 0.45, 0.17, and 0.14, respectively. Among HIV-positive individuals, only TGF-β1 rs1800470 (GG vs AA), APOL1 (in the recessive model), and hypertension were associated with prevalent CKD (adjusted ORs of 0.44 [95% CI, 0.20-0.97], 2.54 [95% CI, 1.44-4.51], and 2.17 [95% CI, 1.35-3.48], respectively). No SNP polymorphisms were associated with prevalent CKD among HIV-negative individuals. LIMITATIONS: The lack of histopathology data for proper categorization of the type of HIV-related nephropathy. CONCLUSIONS:APOL1 polymorphisms were highly prevalent in this population and among adult patientsinfected with HIV and were associated with increased CKD risk. The TGF-β1 (rs1800470) polymorphism was associated with reduced risk, and HMOX1 polymorphisms were unassociated with CKD.
Authors: Barry I Freedman; Wylie Burke; Jasmin Divers; Lucy Eberhard; Crystal A Gadegbeku; Rasheed Gbadegesin; Michael E Hall; Tiffany Jones-Smith; Richard Knight; Jeffrey B Kopp; Csaba P Kovesdy; Keith C Norris; Opeyemi A Olabisi; Glenda V Roberts; John R Sedor; Erika Blacksher Journal: J Am Soc Nephrol Date: 2021-04-14 Impact factor: 14.978
Authors: Rachel K Y Hung; Elizabeth Binns-Roemer; John W Booth; Rachel Hilton; Mark Harber; Beatriz Santana-Suarez; Lucy Campbell; Julie Fox; Andrew Ustianowski; Catherine Cosgrove; James E Burns; Amanda Clarke; David A Price; David Chadwick; Denis Onyango; Lisa Hamzah; Kate Bramham; Caroline A Sabin; Cheryl A Winkler; Frank A Post Journal: Kidney Int Rep Date: 2022-01-25