Genome-Wide Association Study of Orthostatic Hypotension and Supine-Standing Blood Pressure Changes in Two Korean Populations
Orthostatic hypotension (OH) is defined by a 20-mm Hg difference of systolic blood pressure (dtSBP) and/or a 10-mm Hg difference of diastolic blood pressure (dtDBP) between supine and standing, and OH is associated with a failure of the cardiovascular reflex to maintain blood pressure on standing fr...
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BioMed Central
2013-09-01
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| Series: | Genomics & Informatics |
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| Online Access: | http://genominfo.org/upload/pdf/gni-11-129.pdf |
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| author | Kyung-Won Hong Sung Soo Kim Yeonjung Kim |
| author_facet | Kyung-Won Hong Sung Soo Kim Yeonjung Kim |
| author_sort | Kyung-Won Hong |
| collection | DOAJ |
| description | Orthostatic hypotension (OH) is defined by a 20-mm Hg difference of systolic blood pressure (dtSBP) and/or a 10-mm Hg difference of diastolic blood pressure (dtDBP) between supine and standing, and OH is associated with a failure of the cardiovascular reflex to maintain blood pressure on standing from a supine position. To understand the underlying genetic factors for OH traits (OH, dtSBP, and dtDBP), genome-wide association studies (GWASs) using 333,651 single nucleotide polymorphisms (SNPs) were conducted separately for two population-based cohorts, Ansung (n = 3,173) and Ansan (n = 3,255). We identified 8 SNPs (5 SNPs for dtSBP and 3 SNPs for dtDBP) that were repeatedly associated in both the Ansung and Ansan cohorts and had p-values of <1 × 10-5 in the meta-analysis. Unfortunately, the SNPs of the OH case control GWAS did not pass our p-value criteria. Four of 8 SNPs were located in the intergenic region of chromosome 2, and the nearest gene (CTNNA2) was located at 1 Mb of distance. CTNNA2 is a linker between cadherin adhesion receptors and the actin cytoskeleton and is essential for stabilizing dendritic spines in rodent hippocampal neurons. Although there is no report about the function in blood pressure regulation, hippocampal neurons interact primarily with the autonomic nervous system and might be related to OH. The remaining SNPs, rs7098785 of dtSBP trait and rs6892553, rs16887217, and rs4959677 of dtDBP trait were located in the PIK3AP1 intron, ACTBL2-3' flanking, STAR intron, and intergenic region, respectively, but there was no clear functional link to blood pressure regulation. |
| format | Article |
| id | doaj-art-9293c2611d0f42ac9ee85046438da4a3 |
| institution | Kabale University |
| issn | 1598-866X 2234-0742 |
| language | English |
| publishDate | 2013-09-01 |
| publisher | BioMed Central |
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| series | Genomics & Informatics |
| spelling | doaj-art-9293c2611d0f42ac9ee85046438da4a32025-02-02T02:10:27ZengBioMed CentralGenomics & Informatics1598-866X2234-07422013-09-0111312913410.5808/GI.2013.11.3.12945Genome-Wide Association Study of Orthostatic Hypotension and Supine-Standing Blood Pressure Changes in Two Korean PopulationsKyung-Won Hong0Sung Soo Kim1Yeonjung Kim2Division of Epidemiology and Health Index, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongwon 363-951, Korea.Division of Epidemiology and Health Index, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongwon 363-951, Korea.Division of Epidemiology and Health Index, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongwon 363-951, Korea.Orthostatic hypotension (OH) is defined by a 20-mm Hg difference of systolic blood pressure (dtSBP) and/or a 10-mm Hg difference of diastolic blood pressure (dtDBP) between supine and standing, and OH is associated with a failure of the cardiovascular reflex to maintain blood pressure on standing from a supine position. To understand the underlying genetic factors for OH traits (OH, dtSBP, and dtDBP), genome-wide association studies (GWASs) using 333,651 single nucleotide polymorphisms (SNPs) were conducted separately for two population-based cohorts, Ansung (n = 3,173) and Ansan (n = 3,255). We identified 8 SNPs (5 SNPs for dtSBP and 3 SNPs for dtDBP) that were repeatedly associated in both the Ansung and Ansan cohorts and had p-values of <1 × 10-5 in the meta-analysis. Unfortunately, the SNPs of the OH case control GWAS did not pass our p-value criteria. Four of 8 SNPs were located in the intergenic region of chromosome 2, and the nearest gene (CTNNA2) was located at 1 Mb of distance. CTNNA2 is a linker between cadherin adhesion receptors and the actin cytoskeleton and is essential for stabilizing dendritic spines in rodent hippocampal neurons. Although there is no report about the function in blood pressure regulation, hippocampal neurons interact primarily with the autonomic nervous system and might be related to OH. The remaining SNPs, rs7098785 of dtSBP trait and rs6892553, rs16887217, and rs4959677 of dtDBP trait were located in the PIK3AP1 intron, ACTBL2-3' flanking, STAR intron, and intergenic region, respectively, but there was no clear functional link to blood pressure regulation.http://genominfo.org/upload/pdf/gni-11-129.pdfgenome-wide association studyhuman CTNNA2 proteinorthostatic hypotensionsingle nucleotide polymorphism |
| spellingShingle | Kyung-Won Hong Sung Soo Kim Yeonjung Kim Genome-Wide Association Study of Orthostatic Hypotension and Supine-Standing Blood Pressure Changes in Two Korean Populations Genomics & Informatics genome-wide association study human CTNNA2 protein orthostatic hypotension single nucleotide polymorphism |
| title | Genome-Wide Association Study of Orthostatic Hypotension and Supine-Standing Blood Pressure Changes in Two Korean Populations |
| title_full | Genome-Wide Association Study of Orthostatic Hypotension and Supine-Standing Blood Pressure Changes in Two Korean Populations |
| title_fullStr | Genome-Wide Association Study of Orthostatic Hypotension and Supine-Standing Blood Pressure Changes in Two Korean Populations |
| title_full_unstemmed | Genome-Wide Association Study of Orthostatic Hypotension and Supine-Standing Blood Pressure Changes in Two Korean Populations |
| title_short | Genome-Wide Association Study of Orthostatic Hypotension and Supine-Standing Blood Pressure Changes in Two Korean Populations |
| title_sort | genome wide association study of orthostatic hypotension and supine standing blood pressure changes in two korean populations |
| topic | genome-wide association study human CTNNA2 protein orthostatic hypotension single nucleotide polymorphism |
| url | http://genominfo.org/upload/pdf/gni-11-129.pdf |
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