Polymorphism of the endothelin-1 gene (rs5370) is a potential contributor to sickle cell disease pathophysiology
Sickle cell disease has been shown to demonstrate extensive variability in disease severity among and between individuals, the variability highlighted by differing genetic haplotypes. Despite the abundance of reports of functional significance due to polymorphisms of endothelial nitric oxide synthas...
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KeAi Communications Co., Ltd.
2016-12-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304216300381 |
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| author | Kristen G. Navarro Smith E. Agyingi Chinedu K. Nwabuobi Bolaji N. Thomas |
| author_facet | Kristen G. Navarro Smith E. Agyingi Chinedu K. Nwabuobi Bolaji N. Thomas |
| author_sort | Kristen G. Navarro |
| collection | DOAJ |
| description | Sickle cell disease has been shown to demonstrate extensive variability in disease severity among and between individuals, the variability highlighted by differing genetic haplotypes. Despite the abundance of reports of functional significance due to polymorphisms of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) genes, the role of these polymorphisms in mediating sickle cell disease pathophysiology among African Americans is presently unclear. To deconvolute their potential significance among African Americans with sickle cell disease, we examined the genetic diversity and haplotype frequency of eNOS and ET-1 polymorphisms in disease (n = 331) and control (n = 379) groups, with a polymerase–chain reaction restriction fragment length polymorphism assay. We report that genotypic and allelic frequencies of eNOS variants are not significantly different between groups. eNOS homozygote mutants, which had been shown to have clinical significance elsewhere, showed no statistical significance in our study. On the other hand, and contrary to previous report among Africans with sickle cell disease, the endothelin-1 homozygous mutant variant showed significant difference in genotypic (p = 2.84E-12) and allelic frequencies (p = 2.20E-16) between groups. The most common haplotype is the combination of T786C homozygote wild-type variant with homozygote mutant variants of G5665T (ET-1) and Glu298Asp (eNOS). These results show that endothelin-1 (rs5370) polymorphism, rather than endothelial nitric oxide synthase polymorphism might play a significant role in disease severity or individual clinical outcomes among African Americans with sickle cell disease. This would have profound implications for designing and/or advancing personalized care for sickle cell patients and relieving disease complications. |
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| language | English |
| last_indexed | 2024-03-12T20:09:41Z |
| publishDate | 2016-12-01 |
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| series | Genes and Diseases |
| spelling | doaj.art-68362b8dea1c4975bcf323f7e196f5392023-08-02T01:47:32ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422016-12-013429429810.1016/j.gendis.2016.09.002Polymorphism of the endothelin-1 gene (rs5370) is a potential contributor to sickle cell disease pathophysiologyKristen G. Navarro0Smith E. Agyingi1Chinedu K. Nwabuobi2Bolaji N. Thomas3Department of Biomedical Sciences, Rochester Institute of Technology, Rochester, NY, 14623, USADepartment of Biomedical Sciences, Rochester Institute of Technology, Rochester, NY, 14623, USADepartment of Obstetrics and Gynecology, University of South Florida, Tampa, FL, USADepartment of Biomedical Sciences, Rochester Institute of Technology, Rochester, NY, 14623, USASickle cell disease has been shown to demonstrate extensive variability in disease severity among and between individuals, the variability highlighted by differing genetic haplotypes. Despite the abundance of reports of functional significance due to polymorphisms of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) genes, the role of these polymorphisms in mediating sickle cell disease pathophysiology among African Americans is presently unclear. To deconvolute their potential significance among African Americans with sickle cell disease, we examined the genetic diversity and haplotype frequency of eNOS and ET-1 polymorphisms in disease (n = 331) and control (n = 379) groups, with a polymerase–chain reaction restriction fragment length polymorphism assay. We report that genotypic and allelic frequencies of eNOS variants are not significantly different between groups. eNOS homozygote mutants, which had been shown to have clinical significance elsewhere, showed no statistical significance in our study. On the other hand, and contrary to previous report among Africans with sickle cell disease, the endothelin-1 homozygous mutant variant showed significant difference in genotypic (p = 2.84E-12) and allelic frequencies (p = 2.20E-16) between groups. The most common haplotype is the combination of T786C homozygote wild-type variant with homozygote mutant variants of G5665T (ET-1) and Glu298Asp (eNOS). These results show that endothelin-1 (rs5370) polymorphism, rather than endothelial nitric oxide synthase polymorphism might play a significant role in disease severity or individual clinical outcomes among African Americans with sickle cell disease. This would have profound implications for designing and/or advancing personalized care for sickle cell patients and relieving disease complications.http://www.sciencedirect.com/science/article/pii/S2352304216300381Endothelial nitric oxide synthaseEndothelin-1PathophysiologyPolymorphismsSickle cell disease |
| spellingShingle | Kristen G. Navarro Smith E. Agyingi Chinedu K. Nwabuobi Bolaji N. Thomas Polymorphism of the endothelin-1 gene (rs5370) is a potential contributor to sickle cell disease pathophysiology Genes and Diseases Endothelial nitric oxide synthase Endothelin-1 Pathophysiology Polymorphisms Sickle cell disease |
| title | Polymorphism of the endothelin-1 gene (rs5370) is a potential contributor to sickle cell disease pathophysiology |
| title_full | Polymorphism of the endothelin-1 gene (rs5370) is a potential contributor to sickle cell disease pathophysiology |
| title_fullStr | Polymorphism of the endothelin-1 gene (rs5370) is a potential contributor to sickle cell disease pathophysiology |
| title_full_unstemmed | Polymorphism of the endothelin-1 gene (rs5370) is a potential contributor to sickle cell disease pathophysiology |
| title_short | Polymorphism of the endothelin-1 gene (rs5370) is a potential contributor to sickle cell disease pathophysiology |
| title_sort | polymorphism of the endothelin 1 gene rs5370 is a potential contributor to sickle cell disease pathophysiology |
| topic | Endothelial nitric oxide synthase Endothelin-1 Pathophysiology Polymorphisms Sickle cell disease |
| url | http://www.sciencedirect.com/science/article/pii/S2352304216300381 |
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