Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association
Low levels of high-density cholesterol (HDLc) accompany chronic kidney disease, but the association between HDLc and the estimated glomerular filtration rate (eGFR) in the general population is unclear. We investigated the HDLc-eGFR association in nondiabetic Han Chinese (HC, n=1100), West Africans...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Nephrology |
| Online Access: | http://dx.doi.org/10.1155/2012/748984 |
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| author | Amy Rebecca Bentley Ayo P. Doumatey Guanjie Chen Hanxia Huang Jie Zhou Daniel Shriner CongQing Jiang Zhenjian Zhang Guozheng Liu Olufemi Fasanmade Thomas Johnson Johnnie Oli Godfrey Okafor Benjamin A. Eghan Kofi Agyenim-Boateng Jokotade Adeleye Williams Balogun Clement Adebamowo Albert Amoah Joseph Acheampong Adebowale Adeyemo Charles N. Rotimi |
| author_facet | Amy Rebecca Bentley Ayo P. Doumatey Guanjie Chen Hanxia Huang Jie Zhou Daniel Shriner CongQing Jiang Zhenjian Zhang Guozheng Liu Olufemi Fasanmade Thomas Johnson Johnnie Oli Godfrey Okafor Benjamin A. Eghan Kofi Agyenim-Boateng Jokotade Adeleye Williams Balogun Clement Adebamowo Albert Amoah Joseph Acheampong Adebowale Adeyemo Charles N. Rotimi |
| author_sort | Amy Rebecca Bentley |
| collection | DOAJ |
| description | Low levels of high-density cholesterol (HDLc) accompany chronic kidney disease, but the association between HDLc and the estimated glomerular filtration rate (eGFR) in the general population is unclear. We investigated the HDLc-eGFR association in nondiabetic Han Chinese (HC, n=1100), West Africans (WA, n=1497), and African Americans (AA, n=1539). There were significant differences by ancestry: HDLc was positively associated with eGFR in HC (β=0.13, P<0.0001), but negatively associated among African ancestry populations (WA: −0.19, P<0.0001; AA: −0.09, P=0.02). These differences were also seen in nationally-representative NHANES data (among European Americans: 0.09, P=0.005; among African Americans −0.14, P=0.03). To further explore the findings in African ancestry populations, we investigated the role of an African ancestry-specific nephropathy risk variant, rs73885319, in the gene encoding HDL-associated APOL1. Among AA, an inverse HDLc-eGFR association was observed only with the risk genotype (−0.38 versus 0.001; P=0.03). This interaction was not seen in WA.
In summary, counter to expectation, an inverse HDLc-eGFR association was observed among those of African ancestry. Given the APOL1 × HDLc interaction among AA, genetic factors may contribute to this paradoxical association. Notably, these findings suggest that the unexplained mechanism by which APOL1 affects kidney-disease risk may involve HDLc. |
| format | Article |
| id | doaj-art-0a5a7ed3ea0e4c06bd2842639446f020 |
| institution | Kabale University |
| issn | 2090-214X 2090-2158 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Nephrology |
| spelling | doaj-art-0a5a7ed3ea0e4c06bd2842639446f0202025-02-03T06:06:25ZengWileyInternational Journal of Nephrology2090-214X2090-21582012-01-01201210.1155/2012/748984748984Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function AssociationAmy Rebecca Bentley0Ayo P. Doumatey1Guanjie Chen2Hanxia Huang3Jie Zhou4Daniel Shriner5CongQing Jiang6Zhenjian Zhang7Guozheng Liu8Olufemi Fasanmade9Thomas Johnson10Johnnie Oli11Godfrey Okafor12Benjamin A. Eghan13Kofi Agyenim-Boateng14Jokotade Adeleye15Williams Balogun16Clement Adebamowo17Albert Amoah18Joseph Acheampong19Adebowale Adeyemo20Charles N. Rotimi21Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-5635, USACenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-5635, USACenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-5635, USACenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-5635, USACenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-5635, USACenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-5635, USASuizhou Central Hospital, Suizhou, Hubei 441300, ChinaSuizhou Central Hospital, Suizhou, Hubei 441300, ChinaSuizhou Central Hospital, Suizhou, Hubei 441300, ChinaDepartment of Medicine, University of Lagos, Lagos 101017, NigeriaDepartment of Medicine, University of Lagos, Lagos 101017, NigeriaDepartment of Medicine, University of Nigeria Teaching Hospital, Enugu 400001, NigeriaDepartment of Medicine, University of Nigeria Teaching Hospital, Enugu 400001, NigeriaDepartment of Medicine, University of Science and Technology, Kumasi, GhanaDepartment of Medicine, University of Science and Technology, Kumasi, GhanaDepartment of Medicine, University of Ibadan, Ibadan 200284, NigeriaDepartment of Medicine, University of Ibadan, Ibadan 200284, NigeriaDepartment of Medicine, University of Ibadan, Ibadan 200284, NigeriaDepartment of Medicine and Therapeutics, University of Ghana Medical School, Accra, GhanaDepartment of Medicine, University of Science and Technology, Kumasi, GhanaCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-5635, USACenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-5635, USALow levels of high-density cholesterol (HDLc) accompany chronic kidney disease, but the association between HDLc and the estimated glomerular filtration rate (eGFR) in the general population is unclear. We investigated the HDLc-eGFR association in nondiabetic Han Chinese (HC, n=1100), West Africans (WA, n=1497), and African Americans (AA, n=1539). There were significant differences by ancestry: HDLc was positively associated with eGFR in HC (β=0.13, P<0.0001), but negatively associated among African ancestry populations (WA: −0.19, P<0.0001; AA: −0.09, P=0.02). These differences were also seen in nationally-representative NHANES data (among European Americans: 0.09, P=0.005; among African Americans −0.14, P=0.03). To further explore the findings in African ancestry populations, we investigated the role of an African ancestry-specific nephropathy risk variant, rs73885319, in the gene encoding HDL-associated APOL1. Among AA, an inverse HDLc-eGFR association was observed only with the risk genotype (−0.38 versus 0.001; P=0.03). This interaction was not seen in WA. In summary, counter to expectation, an inverse HDLc-eGFR association was observed among those of African ancestry. Given the APOL1 × HDLc interaction among AA, genetic factors may contribute to this paradoxical association. Notably, these findings suggest that the unexplained mechanism by which APOL1 affects kidney-disease risk may involve HDLc.http://dx.doi.org/10.1155/2012/748984 |
| spellingShingle | Amy Rebecca Bentley Ayo P. Doumatey Guanjie Chen Hanxia Huang Jie Zhou Daniel Shriner CongQing Jiang Zhenjian Zhang Guozheng Liu Olufemi Fasanmade Thomas Johnson Johnnie Oli Godfrey Okafor Benjamin A. Eghan Kofi Agyenim-Boateng Jokotade Adeleye Williams Balogun Clement Adebamowo Albert Amoah Joseph Acheampong Adebowale Adeyemo Charles N. Rotimi Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association International Journal of Nephrology |
| title | Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association |
| title_full | Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association |
| title_fullStr | Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association |
| title_full_unstemmed | Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association |
| title_short | Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association |
| title_sort | variation in apol1 contributes to ancestry level differences in hdlc kidney function association |
| url | http://dx.doi.org/10.1155/2012/748984 |
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