Association of Genetic Polymorphisms of TGF-β1, HMOX1, and APOL1 With CKD in Nigerian Patients With and Without HIV
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Bibliographic record
Abstract
Rationale & ObjectiveRecent 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 DesignCase-control study.Setting & ParticipantsWest 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).ExposureThe 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.OutcomeCKD.Analytical ApproachSingle-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.ResultsMinor 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.LimitationsThe lack of histopathology data for proper categorization of the type of HIV-related nephropathy.ConclusionsAPOL1 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. 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. Case-control study. 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). 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. CKD. 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. 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. The lack of histopathology data for proper categorization of the type of HIV-related nephropathy. 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.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it