Association between APOL1 risk variants and the occurrence of sepsis in Black patients hospitalized with infections: a retrospective cohort study
Background: Two risk variants in the apolipoprotein L1 gene (APOL1) have been associated with increased susceptibility to sepsis in Black patients. However, it remains unclear whether APOL1 high-risk genotypes are associated with occurrence of either sepsis or sepsis-related phenotypes in patients h...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/88538 |
| _version_ | 1827782783058051072 |
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| author | Lan Jiang Ge Liu Annette Oeser Andrea Ihegword Alyson L Dickson Laura L Daniel Adriana M Hung Nancy J Cox Cecilia P Chung Wei-Qi Wei C Michael Stein Qiping Feng |
| author_facet | Lan Jiang Ge Liu Annette Oeser Andrea Ihegword Alyson L Dickson Laura L Daniel Adriana M Hung Nancy J Cox Cecilia P Chung Wei-Qi Wei C Michael Stein Qiping Feng |
| author_sort | Lan Jiang |
| collection | DOAJ |
| description | Background: Two risk variants in the apolipoprotein L1 gene (APOL1) have been associated with increased susceptibility to sepsis in Black patients. However, it remains unclear whether APOL1 high-risk genotypes are associated with occurrence of either sepsis or sepsis-related phenotypes in patients hospitalized with infections, independent of their association with pre-existing severe renal disease.
Methods: A retrospective cohort study of 2242 Black patients hospitalized with infections. We assessed whether carriage of APOL1 high-risk genotypes was associated with the risk of sepsis and sepsis-related phenotypes in patients hospitalized with infections. The primary outcome was sepsis; secondary outcomes were short-term mortality, and organ failure related to sepsis.
Results: Of 2242 Black patients hospitalized with infections, 565 developed sepsis. Patients with high-risk APOL1 genotypes had a significantly increased risk of sepsis (odds ratio [OR]=1.29 [95% CI, 1.00–1.67; p=0.047]); however, this association was not significant after adjustment for pre-existing severe renal disease (OR = 1.14 [95% CI, 0.88–1.48; p=0.33]), nor after exclusion of those patients with pre-existing severe renal disease (OR = 0.99 [95% CI, 0.70–1.39; p=0.95]). APOL1 high-risk genotypes were significantly associated with the renal dysfunction component of the Sepsis-3 criteria (OR = 1.64 [95% CI, 1.21–2.22; p=0.001]), but not with other sepsis-related organ dysfunction or short-term mortality. The association between high-risk APOL1 genotypes and sepsis-related renal dysfunction was markedly attenuated by adjusting for pre-existing severe renal disease (OR = 1.36 [95% CI, 1.00–1.86; p=0.05]) and was nullified after exclusion of patients with pre-existing severe renal disease (OR = 1.16 [95% CI, 0.74–1.81; p=0.52]).
Conclusions: APOL1 high-risk genotypes were associated with an increased risk of sepsis; however, this increased risk was attributable predominantly to pre-existing severe renal disease.
Funding: This study was supported by R01GM120523 (QF), R01HL163854 (QF), R35GM131770 (CMS), HL133786 (WQW), and Vanderbilt Faculty Research Scholar Fund (QF). The dataset(s) used for the analyses described were obtained from Vanderbilt University Medical Center’s BioVU which is supported by institutional funding, the 1S10RR025141-01 instrumentation award, and by the CTSA grant UL1TR0004from NCATS/NIH. Additional funding provided by the NIH through grants P50GM115305 and U19HL065962. The authors wish to acknowledge the expert technical support of the VANTAGE and VANGARD core facilities, supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA068485) and Vanderbilt Vision Center (P30 EY08126). The funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. |
| first_indexed | 2024-03-11T15:37:58Z |
| format | Article |
| id | doaj.art-3baa0f4a81db461eb55066a00231d9f0 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-11T15:37:58Z |
| publishDate | 2023-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3baa0f4a81db461eb55066a00231d9f02023-10-26T13:22:07ZengeLife Sciences Publications LtdeLife2050-084X2023-10-011210.7554/eLife.88538Association between APOL1 risk variants and the occurrence of sepsis in Black patients hospitalized with infections: a retrospective cohort studyLan Jiang0Ge Liu1Annette Oeser2Andrea Ihegword3Alyson L Dickson4https://orcid.org/0000-0003-3404-3802Laura L Daniel5https://orcid.org/0000-0003-3143-5915Adriana M Hung6Nancy J Cox7Cecilia P Chung8Wei-Qi Wei9C Michael Stein10Qiping Feng11https://orcid.org/0000-0002-6213-793XDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United StatesDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, United StatesDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United StatesDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United StatesDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States; Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United StatesDivision of Rheumatology, Department of Medicine, University of Miami, Miami, United StatesTennessee Valley Healthcare System, Nashville Campus, Nashville, United States; Division of Nephrology & Hypertension, Vanderbilt University Medical Center, Nashville, United StatesVanderbilt Genetics Institute, Department of Medicine, Vanderbilt University Medical Center, Nashville, United StatesDivision of Rheumatology, Department of Medicine, University of Miami, Miami, United StatesDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, United StatesDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States; Department of Pharmacology, Vanderbilt University, Nashville, United StatesDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States; Vanderbilt Genetics Institute, Department of Medicine, Vanderbilt University Medical Center, Nashville, United StatesBackground: Two risk variants in the apolipoprotein L1 gene (APOL1) have been associated with increased susceptibility to sepsis in Black patients. However, it remains unclear whether APOL1 high-risk genotypes are associated with occurrence of either sepsis or sepsis-related phenotypes in patients hospitalized with infections, independent of their association with pre-existing severe renal disease. Methods: A retrospective cohort study of 2242 Black patients hospitalized with infections. We assessed whether carriage of APOL1 high-risk genotypes was associated with the risk of sepsis and sepsis-related phenotypes in patients hospitalized with infections. The primary outcome was sepsis; secondary outcomes were short-term mortality, and organ failure related to sepsis. Results: Of 2242 Black patients hospitalized with infections, 565 developed sepsis. Patients with high-risk APOL1 genotypes had a significantly increased risk of sepsis (odds ratio [OR]=1.29 [95% CI, 1.00–1.67; p=0.047]); however, this association was not significant after adjustment for pre-existing severe renal disease (OR = 1.14 [95% CI, 0.88–1.48; p=0.33]), nor after exclusion of those patients with pre-existing severe renal disease (OR = 0.99 [95% CI, 0.70–1.39; p=0.95]). APOL1 high-risk genotypes were significantly associated with the renal dysfunction component of the Sepsis-3 criteria (OR = 1.64 [95% CI, 1.21–2.22; p=0.001]), but not with other sepsis-related organ dysfunction or short-term mortality. The association between high-risk APOL1 genotypes and sepsis-related renal dysfunction was markedly attenuated by adjusting for pre-existing severe renal disease (OR = 1.36 [95% CI, 1.00–1.86; p=0.05]) and was nullified after exclusion of patients with pre-existing severe renal disease (OR = 1.16 [95% CI, 0.74–1.81; p=0.52]). Conclusions: APOL1 high-risk genotypes were associated with an increased risk of sepsis; however, this increased risk was attributable predominantly to pre-existing severe renal disease. Funding: This study was supported by R01GM120523 (QF), R01HL163854 (QF), R35GM131770 (CMS), HL133786 (WQW), and Vanderbilt Faculty Research Scholar Fund (QF). The dataset(s) used for the analyses described were obtained from Vanderbilt University Medical Center’s BioVU which is supported by institutional funding, the 1S10RR025141-01 instrumentation award, and by the CTSA grant UL1TR0004from NCATS/NIH. Additional funding provided by the NIH through grants P50GM115305 and U19HL065962. The authors wish to acknowledge the expert technical support of the VANTAGE and VANGARD core facilities, supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA068485) and Vanderbilt Vision Center (P30 EY08126). The funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.https://elifesciences.org/articles/88538sepsisAPOL1African ancestryelectronic health records |
| spellingShingle | Lan Jiang Ge Liu Annette Oeser Andrea Ihegword Alyson L Dickson Laura L Daniel Adriana M Hung Nancy J Cox Cecilia P Chung Wei-Qi Wei C Michael Stein Qiping Feng Association between APOL1 risk variants and the occurrence of sepsis in Black patients hospitalized with infections: a retrospective cohort study eLife sepsis APOL1 African ancestry electronic health records |
| title | Association between APOL1 risk variants and the occurrence of sepsis in Black patients hospitalized with infections: a retrospective cohort study |
| title_full | Association between APOL1 risk variants and the occurrence of sepsis in Black patients hospitalized with infections: a retrospective cohort study |
| title_fullStr | Association between APOL1 risk variants and the occurrence of sepsis in Black patients hospitalized with infections: a retrospective cohort study |
| title_full_unstemmed | Association between APOL1 risk variants and the occurrence of sepsis in Black patients hospitalized with infections: a retrospective cohort study |
| title_short | Association between APOL1 risk variants and the occurrence of sepsis in Black patients hospitalized with infections: a retrospective cohort study |
| title_sort | association between apol1 risk variants and the occurrence of sepsis in black patients hospitalized with infections a retrospective cohort study |
| topic | sepsis APOL1 African ancestry electronic health records |
| url | https://elifesciences.org/articles/88538 |
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