Association of FMO3 Variants with Blood Pressure in the Atherosclerosis Risk in Communities Study
Flavin containing monooxygenase 3 [FMO3] encodes dimethylaniline monooxygenase [N-oxide-forming] 3, which breaks down nitrogen-containing compounds, and has been implicated in blood pressure regulation. Studies have reported conflicting results of the association of a common nonsynonymous variant, E...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | International Journal of Hypertension |
| Online Access: | http://dx.doi.org/10.1155/2019/2137629 |
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| author | Tyler S. Bryant Priya Duggal Bing Yu Alanna C. Morrison Tariq Shafi Georg Ehret Nora Franceschini Eric Boerwinkle Josef Coresh Adrienne Tin |
| author_facet | Tyler S. Bryant Priya Duggal Bing Yu Alanna C. Morrison Tariq Shafi Georg Ehret Nora Franceschini Eric Boerwinkle Josef Coresh Adrienne Tin |
| author_sort | Tyler S. Bryant |
| collection | DOAJ |
| description | Flavin containing monooxygenase 3 [FMO3] encodes dimethylaniline monooxygenase [N-oxide-forming] 3, which breaks down nitrogen-containing compounds, and has been implicated in blood pressure regulation. Studies have reported conflicting results of the association of a common nonsynonymous variant, E158K (rs2266782), with hypertension. We examined the associations of E158K, along with rare and low frequency exonic variants (minor allele frequency [MAF]<5%) in FMO3 with hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP). We included 7,350 European Americans and 2,814 African Americans in the Atherosclerosis Risk in Communities (ARIC) study with exome sequencing of FMO3. The association of FMO3 variants with SBP and DBP was tested using single variant and gene-based tests followed by the replication or interrogation of significant variants in ancestry-specific cohorts based on Bonferroni corrected thresholds. E158K had significant association with higher SBP in African Americans in ARIC (p=0.03), and two low frequency variants had significant association with higher SBP in African Americans (rs200985584, MAF 0.1%, p=0.0003) and European Americans (rs75904274, MAF 1.7%, p=0.006). These associations were not significant with additional samples: E158K in a meta-analysis of SBP of African ancestry (N=30,841, p=0.43) that included ARIC participants and the two low frequency variants in an independent ancestry-specific exome sequencing study of blood pressure (rs200985584, p=0.94; rs75904274, p=0.81). Our study does not support the association of E158K and low frequency variants in FMO3 with blood pressure and demonstrates the importance of replication in genetic studies. |
| format | Article |
| id | doaj-art-508061a1c38349c581446ab1a9670f68 |
| institution | Kabale University |
| issn | 2090-0384 2090-0392 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Hypertension |
| spelling | doaj-art-508061a1c38349c581446ab1a9670f682025-02-03T01:31:16ZengWileyInternational Journal of Hypertension2090-03842090-03922019-01-01201910.1155/2019/21376292137629Association of FMO3 Variants with Blood Pressure in the Atherosclerosis Risk in Communities StudyTyler S. Bryant0Priya Duggal1Bing Yu2Alanna C. Morrison3Tariq Shafi4Georg Ehret5Nora Franceschini6Eric Boerwinkle7Josef Coresh8Adrienne Tin9Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USADepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USAHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USAHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USADivision of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD, USACenter for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USAGillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USAHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USADepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USADepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USAFlavin containing monooxygenase 3 [FMO3] encodes dimethylaniline monooxygenase [N-oxide-forming] 3, which breaks down nitrogen-containing compounds, and has been implicated in blood pressure regulation. Studies have reported conflicting results of the association of a common nonsynonymous variant, E158K (rs2266782), with hypertension. We examined the associations of E158K, along with rare and low frequency exonic variants (minor allele frequency [MAF]<5%) in FMO3 with hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP). We included 7,350 European Americans and 2,814 African Americans in the Atherosclerosis Risk in Communities (ARIC) study with exome sequencing of FMO3. The association of FMO3 variants with SBP and DBP was tested using single variant and gene-based tests followed by the replication or interrogation of significant variants in ancestry-specific cohorts based on Bonferroni corrected thresholds. E158K had significant association with higher SBP in African Americans in ARIC (p=0.03), and two low frequency variants had significant association with higher SBP in African Americans (rs200985584, MAF 0.1%, p=0.0003) and European Americans (rs75904274, MAF 1.7%, p=0.006). These associations were not significant with additional samples: E158K in a meta-analysis of SBP of African ancestry (N=30,841, p=0.43) that included ARIC participants and the two low frequency variants in an independent ancestry-specific exome sequencing study of blood pressure (rs200985584, p=0.94; rs75904274, p=0.81). Our study does not support the association of E158K and low frequency variants in FMO3 with blood pressure and demonstrates the importance of replication in genetic studies.http://dx.doi.org/10.1155/2019/2137629 |
| spellingShingle | Tyler S. Bryant Priya Duggal Bing Yu Alanna C. Morrison Tariq Shafi Georg Ehret Nora Franceschini Eric Boerwinkle Josef Coresh Adrienne Tin Association of FMO3 Variants with Blood Pressure in the Atherosclerosis Risk in Communities Study International Journal of Hypertension |
| title | Association of FMO3 Variants with Blood Pressure in the Atherosclerosis Risk in Communities Study |
| title_full | Association of FMO3 Variants with Blood Pressure in the Atherosclerosis Risk in Communities Study |
| title_fullStr | Association of FMO3 Variants with Blood Pressure in the Atherosclerosis Risk in Communities Study |
| title_full_unstemmed | Association of FMO3 Variants with Blood Pressure in the Atherosclerosis Risk in Communities Study |
| title_short | Association of FMO3 Variants with Blood Pressure in the Atherosclerosis Risk in Communities Study |
| title_sort | association of fmo3 variants with blood pressure in the atherosclerosis risk in communities study |
| url | http://dx.doi.org/10.1155/2019/2137629 |
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