A variant in the ABO gene explains the variation in soluble E-selectin levels-results from dense genotyping in two independent populations.
<h4>Background</h4>Elevated soluble (s) E-selectin levels have been associated with various cardiovascular diseases. Recently, genetic variants in the ABO blood group have been related to E-selectin levels in a small cohort of patients with type 1 diabetes. We evaluated whether this asso...
Guardado en:
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2012
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/069e8cdec5c740bc98d34fbd81fb41e7 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:069e8cdec5c740bc98d34fbd81fb41e7 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:069e8cdec5c740bc98d34fbd81fb41e72021-11-18T08:03:10ZA variant in the ABO gene explains the variation in soluble E-selectin levels-results from dense genotyping in two independent populations.1932-620310.1371/journal.pone.0051441https://doaj.org/article/069e8cdec5c740bc98d34fbd81fb41e72012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300549/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Elevated soluble (s) E-selectin levels have been associated with various cardiovascular diseases. Recently, genetic variants in the ABO blood group have been related to E-selectin levels in a small cohort of patients with type 1 diabetes. We evaluated whether this association is reproducible in two large samples of Caucasians.<h4>Methodology/ principal findings</h4>Data of the present study was drawn from the population-based MONICA/KORA Augsburg study (n = 1,482) and the patients-based LURIC study (n = 1,546). A high-density genotyping array (50K IBC Chip) containing single-nucleotide polymorphisms (SNPs) from E-selectin candidate genes selected on known biology of E-selectin metabolism, mouse genetic studies, and human genetic association studies, was used for genotyping. Linear regression analyses with adjustment for age and sex (and survey in KORA) were applied to assess associations between gene variants and sE-selectin concentrations. A number of 12 SNPs (in KORA) and 13 SNPs (in LURIC), all from the ABO blood group gene, were significantly associated with the log-transformed concentration of E-selectin. The strongest association was observed for rs651007 with a change of log-transformed sE-selectin per one copy of the minor allele of -0.37 ng/ml (p = 1.87×10(-103)) in KORA and -0.35 ng/ml (p = 5.11×10(-84)) in LURIC. Inclusion of rs651007 increased the explained sE-selectin variance by 0.256 in KORA and 0.213 in LURIC. All SNPs had minor allele frequencies above 20% showing a substantial gene variation.<h4>Conclusions/ significance</h4>Our findings in two independent samples indicate that the genetic variants at the ABO locus affect sE-selectin levels. Since distinct genome-wide association studies linked the ABO gene with myocardial infarction (MI) in the presence of coronary atherosclerosis and with coronary artery disease, these findings may not only enhance our understanding of adhesion molecule biology, but may also provide a focus for several novel research avenues.Mahir KarakasJens BaumertMarcus E KleberBarbara ThorandDhayana DallmeierGünther SilbernagelTanja B GrammerWolfgang RottbauerChrista MeisingerThomas IlligWinfried MärzWolfgang KoenigPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e51441 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Mahir Karakas Jens Baumert Marcus E Kleber Barbara Thorand Dhayana Dallmeier Günther Silbernagel Tanja B Grammer Wolfgang Rottbauer Christa Meisinger Thomas Illig Winfried März Wolfgang Koenig A variant in the ABO gene explains the variation in soluble E-selectin levels-results from dense genotyping in two independent populations. |
| description |
<h4>Background</h4>Elevated soluble (s) E-selectin levels have been associated with various cardiovascular diseases. Recently, genetic variants in the ABO blood group have been related to E-selectin levels in a small cohort of patients with type 1 diabetes. We evaluated whether this association is reproducible in two large samples of Caucasians.<h4>Methodology/ principal findings</h4>Data of the present study was drawn from the population-based MONICA/KORA Augsburg study (n = 1,482) and the patients-based LURIC study (n = 1,546). A high-density genotyping array (50K IBC Chip) containing single-nucleotide polymorphisms (SNPs) from E-selectin candidate genes selected on known biology of E-selectin metabolism, mouse genetic studies, and human genetic association studies, was used for genotyping. Linear regression analyses with adjustment for age and sex (and survey in KORA) were applied to assess associations between gene variants and sE-selectin concentrations. A number of 12 SNPs (in KORA) and 13 SNPs (in LURIC), all from the ABO blood group gene, were significantly associated with the log-transformed concentration of E-selectin. The strongest association was observed for rs651007 with a change of log-transformed sE-selectin per one copy of the minor allele of -0.37 ng/ml (p = 1.87×10(-103)) in KORA and -0.35 ng/ml (p = 5.11×10(-84)) in LURIC. Inclusion of rs651007 increased the explained sE-selectin variance by 0.256 in KORA and 0.213 in LURIC. All SNPs had minor allele frequencies above 20% showing a substantial gene variation.<h4>Conclusions/ significance</h4>Our findings in two independent samples indicate that the genetic variants at the ABO locus affect sE-selectin levels. Since distinct genome-wide association studies linked the ABO gene with myocardial infarction (MI) in the presence of coronary atherosclerosis and with coronary artery disease, these findings may not only enhance our understanding of adhesion molecule biology, but may also provide a focus for several novel research avenues. |
| format |
article |
| author |
Mahir Karakas Jens Baumert Marcus E Kleber Barbara Thorand Dhayana Dallmeier Günther Silbernagel Tanja B Grammer Wolfgang Rottbauer Christa Meisinger Thomas Illig Winfried März Wolfgang Koenig |
| author_facet |
Mahir Karakas Jens Baumert Marcus E Kleber Barbara Thorand Dhayana Dallmeier Günther Silbernagel Tanja B Grammer Wolfgang Rottbauer Christa Meisinger Thomas Illig Winfried März Wolfgang Koenig |
| author_sort |
Mahir Karakas |
| title |
A variant in the ABO gene explains the variation in soluble E-selectin levels-results from dense genotyping in two independent populations. |
| title_short |
A variant in the ABO gene explains the variation in soluble E-selectin levels-results from dense genotyping in two independent populations. |
| title_full |
A variant in the ABO gene explains the variation in soluble E-selectin levels-results from dense genotyping in two independent populations. |
| title_fullStr |
A variant in the ABO gene explains the variation in soluble E-selectin levels-results from dense genotyping in two independent populations. |
| title_full_unstemmed |
A variant in the ABO gene explains the variation in soluble E-selectin levels-results from dense genotyping in two independent populations. |
| title_sort |
variant in the abo gene explains the variation in soluble e-selectin levels-results from dense genotyping in two independent populations. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/069e8cdec5c740bc98d34fbd81fb41e7 |
| work_keys_str_mv |
AT mahirkarakas avariantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT jensbaumert avariantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT marcusekleber avariantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT barbarathorand avariantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT dhayanadallmeier avariantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT gunthersilbernagel avariantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT tanjabgrammer avariantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT wolfgangrottbauer avariantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT christameisinger avariantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT thomasillig avariantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT winfriedmarz avariantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT wolfgangkoenig avariantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT mahirkarakas variantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT jensbaumert variantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT marcusekleber variantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT barbarathorand variantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT dhayanadallmeier variantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT gunthersilbernagel variantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT tanjabgrammer variantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT wolfgangrottbauer variantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT christameisinger variantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT thomasillig variantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT winfriedmarz variantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations AT wolfgangkoenig variantintheabogeneexplainsthevariationinsolubleeselectinlevelsresultsfromdensegenotypingintwoindependentpopulations |
| _version_ |
1718422585255919616 |