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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Al Maskari, R. Cleary, S. Li, Y. Khir, A. Mitchell, G. Wilkinson, I. O’Shaughnessy, K. Yasmin |
| Abstract | Background Genetic variants in the 3’-BCL11B gene desert on 14q32.3 were recently shown to associate with aortic pulse wave velocity in the AortaGen Consortium GWAS meta-analysis. This region is believed to harbour a gene enhancer targeting BCL11B. We investigated the influence of 5 polymorphisms from this study (rs1381289C>T, rs6485690G>A, rs10782490C>T, rs1461587G>T and rs17773233G>T) on BCL11B mRNA levels and stiffness measured as Young’s Elastic Modulus (EM) in 167 donor aortic tissue samples. Methods Demographic and other data were obtained, and EM was measured using Instron. SNP genotyping and BCL11B gene expression levels were determined using ABI assays. Results Mean age of sample was 57 ± 15 years. As expected, EM correlated significantly with age (r = 0.47, P<0.001). BCL11B gene expression levels were higher in subjects carrying rs1381289 T and rs10782490 C alleles (P <0.05). rs1461587G>T and rs17773233G>T polymorphisms showed genotype specific higher EM values (P<0.05); subjects homozygous for the risk allele had stiffer arteries compared to those who were heterozygous or those who did not carry the allele. Multiple regression adjusted for confounders showed rs1461587G>T and rs17773233G>T associated with increased EM (beta = -0.15, P<0.05) and (beta = 0.17, P<0.05) respectively. Conclusions We have demonstrated for the first time that rs1381289 and rs10782490 have an effect on BCL11B transcription, resulting in different BCL11B gene expression levels among those with different genotypes. In addition, rs1461587G>T and rs17773233G>T polymorphisms influence aortic stiffness measured ex vivo, confirming previous observations. Further functional studies are required to elucidate the role of this locus on aortic stiffness. |
| Related Links | https://arteryresearch.biomedcentral.com/counter/pdf/10.1016/j.artres.2014.09.070.pdf |
| Ending Page | 127 |
| Page Count | 2 |
| Starting Page | 126 |
| File Format | HTM / HTML |
| ISSN | 18764401 |
| DOI | 10.1016/j.artres.2014.09.070 |
| Journal | Artery Research |
| Issue Number | 4 |
| Volume Number | 8 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2014-11-04 |
| Access Restriction | Open |
| Subject Keyword | Medicine Public Health Medicine/Public Health |
| Content Type | Text |
| Resource Type | Synopsis |
| Subject | Physiology (medical) Physiology |
| Journal Impact Factor | 0.9/2023 |
| 5-Year Journal Impact Factor | 0.7/2023 |
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