Assessing known chronic kidney disease associated genetic variants in Saudi Arabian populations
Abstract Background Genome wide association studies of patients with European descent have identified common variants associated with risk of reduced estimated glomerular filtration rate (eGFR). A panel of eight variants were selected to evaluate their association and prevalence in a Saudi Arabian p...
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| Format: | Article |
| Language: | English |
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BMC
2018-04-01
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| Series: | BMC Nephrology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12882-018-0890-9 |
| _version_ | 1818321945394937856 |
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| author | Cyril Cyrus Samir Al-Mueilo Chittibabu Vatte Shahanas Chathoth Yun R. Li Hatem Qutub Rudaynah Al Ali Fahad Al-Muhanna Matthew B. Lanktree Khaled Riyad Alkharsah Abdullah Al-Rubaish Brian Kim-Mozeleski Brendan Keating Amein Al Ali |
| author_facet | Cyril Cyrus Samir Al-Mueilo Chittibabu Vatte Shahanas Chathoth Yun R. Li Hatem Qutub Rudaynah Al Ali Fahad Al-Muhanna Matthew B. Lanktree Khaled Riyad Alkharsah Abdullah Al-Rubaish Brian Kim-Mozeleski Brendan Keating Amein Al Ali |
| author_sort | Cyril Cyrus |
| collection | DOAJ |
| description | Abstract Background Genome wide association studies of patients with European descent have identified common variants associated with risk of reduced estimated glomerular filtration rate (eGFR). A panel of eight variants were selected to evaluate their association and prevalence in a Saudi Arabian patient cohort with chronic kidney disease (CKD). Methods Eight genetic variants in four genes (SHROOM3, MYH9, SLC7A9, and CST3) were genotyped in 160 CKD patients and 189 ethnicity-matched healthy controls. Genetic variants were tested for association with the development of CKD (eGFR < 60 ml/min/1.73m2) and effects were compared with results obtained from 133,413 participants in the CKD genetics consortium. Multivariable regression was used to evaluate the role of these eight variants in improving prediction of CKD development. Results All eight variants were present in Saudi populations with minor allele frequency ranging from 16 to 46%. The risk variant in all four genes demonstrated the same direction of effect as observed in European populations. One variant, rs4821480, in MYH9 was significantly associated with increased risk of development of CKD (OR = 1.69, 95% CI 1.22–2.36, P = 0.002), but the additional variants were not statistically significant given our modest sample size. Conclusions CKD risk variants identified in European populations are present in Saudis. We did not find evidence to suggest heterogeneity of effect size compared to previously published estimates in European populations. Multivariable logistic regression analysis showed a statistically significant improvement in predicting the CKD using models with either FGF23 and vitamin D or FGF23, vitamin D level, and MYH9 genotypes (AUC = 0.93, 95% CI 0.90–0.95, P < 0.0001). |
| first_indexed | 2024-12-13T10:48:58Z |
| format | Article |
| id | doaj.art-3b3c8cb6ce41411ab1b48fc7e404dff9 |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-12-13T10:48:58Z |
| publishDate | 2018-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-3b3c8cb6ce41411ab1b48fc7e404dff92022-12-21T23:49:58ZengBMCBMC Nephrology1471-23692018-04-011911610.1186/s12882-018-0890-9Assessing known chronic kidney disease associated genetic variants in Saudi Arabian populationsCyril Cyrus0Samir Al-Mueilo1Chittibabu Vatte2Shahanas Chathoth3Yun R. Li4Hatem Qutub5Rudaynah Al Ali6Fahad Al-Muhanna7Matthew B. Lanktree8Khaled Riyad Alkharsah9Abdullah Al-Rubaish10Brian Kim-Mozeleski11Brendan Keating12Amein Al Ali13Institute for Research and Medical Consultation, Imam Abdulrahman bin Faisal UniversityKing Fahd Hospital of the University, Imam Abdulrahman bin Faisal UniversityInstitute for Research and Medical Consultation, Imam Abdulrahman bin Faisal UniversityInstitute for Research and Medical Consultation, Imam Abdulrahman bin Faisal UniversityPerelman School of Medicine, University of PennsylvaniaKing Fahd Hospital of the University, Imam Abdulrahman bin Faisal UniversityKing Fahd Hospital of the University, Imam Abdulrahman bin Faisal UniversityKing Fahd Hospital of the University, Imam Abdulrahman bin Faisal UniversityNephrology Division, Department of Medicine, McMaster UniversityInstitute for Research and Medical Consultation, Imam Abdulrahman bin Faisal UniversityKing Fahd Hospital of the University, Imam Abdulrahman bin Faisal UniversityPerelman School of Medicine, University of PennsylvaniaPerelman School of Medicine, University of PennsylvaniaInstitute for Research and Medical Consultation, Imam Abdulrahman bin Faisal UniversityAbstract Background Genome wide association studies of patients with European descent have identified common variants associated with risk of reduced estimated glomerular filtration rate (eGFR). A panel of eight variants were selected to evaluate their association and prevalence in a Saudi Arabian patient cohort with chronic kidney disease (CKD). Methods Eight genetic variants in four genes (SHROOM3, MYH9, SLC7A9, and CST3) were genotyped in 160 CKD patients and 189 ethnicity-matched healthy controls. Genetic variants were tested for association with the development of CKD (eGFR < 60 ml/min/1.73m2) and effects were compared with results obtained from 133,413 participants in the CKD genetics consortium. Multivariable regression was used to evaluate the role of these eight variants in improving prediction of CKD development. Results All eight variants were present in Saudi populations with minor allele frequency ranging from 16 to 46%. The risk variant in all four genes demonstrated the same direction of effect as observed in European populations. One variant, rs4821480, in MYH9 was significantly associated with increased risk of development of CKD (OR = 1.69, 95% CI 1.22–2.36, P = 0.002), but the additional variants were not statistically significant given our modest sample size. Conclusions CKD risk variants identified in European populations are present in Saudis. We did not find evidence to suggest heterogeneity of effect size compared to previously published estimates in European populations. Multivariable logistic regression analysis showed a statistically significant improvement in predicting the CKD using models with either FGF23 and vitamin D or FGF23, vitamin D level, and MYH9 genotypes (AUC = 0.93, 95% CI 0.90–0.95, P < 0.0001).http://link.springer.com/article/10.1186/s12882-018-0890-9Chronic kidney diseaseSNPMYH9SHROOM3Genetic biomarkersSLC7A9 |
| spellingShingle | Cyril Cyrus Samir Al-Mueilo Chittibabu Vatte Shahanas Chathoth Yun R. Li Hatem Qutub Rudaynah Al Ali Fahad Al-Muhanna Matthew B. Lanktree Khaled Riyad Alkharsah Abdullah Al-Rubaish Brian Kim-Mozeleski Brendan Keating Amein Al Ali Assessing known chronic kidney disease associated genetic variants in Saudi Arabian populations BMC Nephrology Chronic kidney disease SNP MYH9 SHROOM3 Genetic biomarkers SLC7A9 |
| title | Assessing known chronic kidney disease associated genetic variants in Saudi Arabian populations |
| title_full | Assessing known chronic kidney disease associated genetic variants in Saudi Arabian populations |
| title_fullStr | Assessing known chronic kidney disease associated genetic variants in Saudi Arabian populations |
| title_full_unstemmed | Assessing known chronic kidney disease associated genetic variants in Saudi Arabian populations |
| title_short | Assessing known chronic kidney disease associated genetic variants in Saudi Arabian populations |
| title_sort | assessing known chronic kidney disease associated genetic variants in saudi arabian populations |
| topic | Chronic kidney disease SNP MYH9 SHROOM3 Genetic biomarkers SLC7A9 |
| url | http://link.springer.com/article/10.1186/s12882-018-0890-9 |
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