Quantitative variation in plasma angiotensin-i converting enzyme activity shows allelic heterogeneity in the ABO blood group locus
Angiotensin-I converting enzyme (ACE) occupies a pivotal role in cardiovascular homeostasis. Major loci for plasma ACE have been identified at ACE on Chromosome 17 and at ABO on Chromosome 9. We sought to characterise the genetic architecture of plasma ACE at finer resolution in two populations. We...
| Asıl Yazarlar: | , , , , , , , , , , , |
|---|---|
| Materyal Türü: | Journal article |
| Dil: | English |
| Baskı/Yayın Bilgisi: |
2013
|
| _version_ | 1826300747960025088 |
|---|---|
| author | Terao, C Bayoumi, N McKenzie, C Zelenika, D Muro, S Mishima, M Connell, J Vickers, M Mark Lathrop, G Farrall, M Matsuda, F Keavney, B |
| author_facet | Terao, C Bayoumi, N McKenzie, C Zelenika, D Muro, S Mishima, M Connell, J Vickers, M Mark Lathrop, G Farrall, M Matsuda, F Keavney, B |
| author_sort | Terao, C |
| collection | OXFORD |
| description | Angiotensin-I converting enzyme (ACE) occupies a pivotal role in cardiovascular homeostasis. Major loci for plasma ACE have been identified at ACE on Chromosome 17 and at ABO on Chromosome 9. We sought to characterise the genetic architecture of plasma ACE at finer resolution in two populations. We carried out a GWAS in 1810 individuals of Japanese ethnicity; this identified signals at ACE and ABO that together accounted for nearly half of the population variability of the trait. We conducted measured haplotype analysis at the ABO locus in 1425 members of 248 British families using haplotypes of three SNPs, which together tagged the alleles responsible for the principal blood group antigens A1, A2, B and O. Type O alleles were associated with intermediate plasma ACE activity compared to Type A1 alleles (in whom plasma ACE activity was ̃36% lower) and Type B alleles (in whom plasma ACE activity was ̃36% higher). We demonstrated heterogeneity among A alleles: A2 alleles were associated with plasma ACE activity that was very similar to the O alleles. Variation at ACE accounted for 35% of the trait variance, and variation at ABO accounted for 15%. A further 10% could be ascribed to polygenic effects. © 2013 John Wiley and Sons Ltd. |
| first_indexed | 2024-03-07T05:21:53Z |
| format | Journal article |
| id | oxford-uuid:df2fd5c9-1e1e-446e-b576-eeef61db7e0d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:21:53Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:df2fd5c9-1e1e-446e-b576-eeef61db7e0d2022-03-27T09:37:49ZQuantitative variation in plasma angiotensin-i converting enzyme activity shows allelic heterogeneity in the ABO blood group locusJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:df2fd5c9-1e1e-446e-b576-eeef61db7e0dEnglishSymplectic Elements at Oxford2013Terao, CBayoumi, NMcKenzie, CZelenika, DMuro, SMishima, MConnell, JVickers, MMark Lathrop, GFarrall, MMatsuda, FKeavney, BAngiotensin-I converting enzyme (ACE) occupies a pivotal role in cardiovascular homeostasis. Major loci for plasma ACE have been identified at ACE on Chromosome 17 and at ABO on Chromosome 9. We sought to characterise the genetic architecture of plasma ACE at finer resolution in two populations. We carried out a GWAS in 1810 individuals of Japanese ethnicity; this identified signals at ACE and ABO that together accounted for nearly half of the population variability of the trait. We conducted measured haplotype analysis at the ABO locus in 1425 members of 248 British families using haplotypes of three SNPs, which together tagged the alleles responsible for the principal blood group antigens A1, A2, B and O. Type O alleles were associated with intermediate plasma ACE activity compared to Type A1 alleles (in whom plasma ACE activity was ̃36% lower) and Type B alleles (in whom plasma ACE activity was ̃36% higher). We demonstrated heterogeneity among A alleles: A2 alleles were associated with plasma ACE activity that was very similar to the O alleles. Variation at ACE accounted for 35% of the trait variance, and variation at ABO accounted for 15%. A further 10% could be ascribed to polygenic effects. © 2013 John Wiley and Sons Ltd. |
| spellingShingle | Terao, C Bayoumi, N McKenzie, C Zelenika, D Muro, S Mishima, M Connell, J Vickers, M Mark Lathrop, G Farrall, M Matsuda, F Keavney, B Quantitative variation in plasma angiotensin-i converting enzyme activity shows allelic heterogeneity in the ABO blood group locus |
| title | Quantitative variation in plasma angiotensin-i converting enzyme activity shows allelic heterogeneity in the ABO blood group locus |
| title_full | Quantitative variation in plasma angiotensin-i converting enzyme activity shows allelic heterogeneity in the ABO blood group locus |
| title_fullStr | Quantitative variation in plasma angiotensin-i converting enzyme activity shows allelic heterogeneity in the ABO blood group locus |
| title_full_unstemmed | Quantitative variation in plasma angiotensin-i converting enzyme activity shows allelic heterogeneity in the ABO blood group locus |
| title_short | Quantitative variation in plasma angiotensin-i converting enzyme activity shows allelic heterogeneity in the ABO blood group locus |
| title_sort | quantitative variation in plasma angiotensin i converting enzyme activity shows allelic heterogeneity in the abo blood group locus |
| work_keys_str_mv | AT teraoc quantitativevariationinplasmaangiotensiniconvertingenzymeactivityshowsallelicheterogeneityintheabobloodgrouplocus AT bayoumin quantitativevariationinplasmaangiotensiniconvertingenzymeactivityshowsallelicheterogeneityintheabobloodgrouplocus AT mckenziec quantitativevariationinplasmaangiotensiniconvertingenzymeactivityshowsallelicheterogeneityintheabobloodgrouplocus AT zelenikad quantitativevariationinplasmaangiotensiniconvertingenzymeactivityshowsallelicheterogeneityintheabobloodgrouplocus AT muros quantitativevariationinplasmaangiotensiniconvertingenzymeactivityshowsallelicheterogeneityintheabobloodgrouplocus AT mishimam quantitativevariationinplasmaangiotensiniconvertingenzymeactivityshowsallelicheterogeneityintheabobloodgrouplocus AT connellj quantitativevariationinplasmaangiotensiniconvertingenzymeactivityshowsallelicheterogeneityintheabobloodgrouplocus AT vickersm quantitativevariationinplasmaangiotensiniconvertingenzymeactivityshowsallelicheterogeneityintheabobloodgrouplocus AT marklathropg quantitativevariationinplasmaangiotensiniconvertingenzymeactivityshowsallelicheterogeneityintheabobloodgrouplocus AT farrallm quantitativevariationinplasmaangiotensiniconvertingenzymeactivityshowsallelicheterogeneityintheabobloodgrouplocus AT matsudaf quantitativevariationinplasmaangiotensiniconvertingenzymeactivityshowsallelicheterogeneityintheabobloodgrouplocus AT keavneyb quantitativevariationinplasmaangiotensiniconvertingenzymeactivityshowsallelicheterogeneityintheabobloodgrouplocus |