TY - JOUR
T1 - The TGFβ system and TIMP1 and 3 genotypes in Turner syndrome-Relation with aortic congenital malformations
AU - Ridder, Lukas Ochsner
AU - Stochholm, Kirstine
AU - Mortensen, Kristian Havmand
AU - Andersen, Niels Holmark
AU - Gravholt, Claus Højbjerg
PY - 2023/12
Y1 - 2023/12
N2 - OBJECTIVE: Cardiovascular complications and congenital malformations are known traits in Turner syndrome (TS), which increases mortality. Women with TS have varying phenotype and cardiovascular risks. A biomarker assessing the risk for cardiovascular complications could potentially reduce mortality in high-risk TS and reduce screening in TS participants with low cardiovascular risk.DESIGN, PATIENTS, PARTICIPANTS AND MEASUREMENTS: As part of a study initiated in 2002, 87 TS participants and 64 controls were invited to magnetic resonance imaging of the aorta, anthropometry, and biochemical markers. TS participants were re-examined thrice lastly in 2016. The focus of this paper is the additional measurements of transforming growth factor beta (TGFβ), matrix metalloproteinase (MMP's), tissue inhibitor of matrix metalloproteinase (TIMP), peripheral blood DNA and their associations with TS and the cardiovascular risk and congenital heart disease.RESULTS: TS participants had lower TGFβ1 and TGFβ2 values compared to controls. snp11547635 heterozygosity was not associated with any biomarkers but was associated with increased risk of aortic regurgitation. TIMP4 and TGFβ1 were correlated with the aortic diameter at several measuring positions. During follow-up, the antihypertensive treatment decreased the descending aortic diameter and increased TGFβ1 and TGFβ2 levels in TS.CONCLUSION: TGFβ and TIMP's are altered in TS and may play a role in the development of coarctation and dilated aorta. snp11547635 heterozygosity was not found to impact biochemical markers. Further studies should investigate these biomarkers to further unravel the pathogenesis of the increased cardiovascular risk in TS participants.
AB - OBJECTIVE: Cardiovascular complications and congenital malformations are known traits in Turner syndrome (TS), which increases mortality. Women with TS have varying phenotype and cardiovascular risks. A biomarker assessing the risk for cardiovascular complications could potentially reduce mortality in high-risk TS and reduce screening in TS participants with low cardiovascular risk.DESIGN, PATIENTS, PARTICIPANTS AND MEASUREMENTS: As part of a study initiated in 2002, 87 TS participants and 64 controls were invited to magnetic resonance imaging of the aorta, anthropometry, and biochemical markers. TS participants were re-examined thrice lastly in 2016. The focus of this paper is the additional measurements of transforming growth factor beta (TGFβ), matrix metalloproteinase (MMP's), tissue inhibitor of matrix metalloproteinase (TIMP), peripheral blood DNA and their associations with TS and the cardiovascular risk and congenital heart disease.RESULTS: TS participants had lower TGFβ1 and TGFβ2 values compared to controls. snp11547635 heterozygosity was not associated with any biomarkers but was associated with increased risk of aortic regurgitation. TIMP4 and TGFβ1 were correlated with the aortic diameter at several measuring positions. During follow-up, the antihypertensive treatment decreased the descending aortic diameter and increased TGFβ1 and TGFβ2 levels in TS.CONCLUSION: TGFβ and TIMP's are altered in TS and may play a role in the development of coarctation and dilated aorta. snp11547635 heterozygosity was not found to impact biochemical markers. Further studies should investigate these biomarkers to further unravel the pathogenesis of the increased cardiovascular risk in TS participants.
KW - TGFβ
KW - Turner syndrome
KW - antihypertensive treatment
KW - cardiovascular risk
KW - snp11547635
KW - tissue inhibitor of matrix metalloproteinase
KW - Humans
KW - Genotype
KW - Turner Syndrome/complications
KW - Matrix Metalloproteinases/genetics
KW - Tissue Inhibitor of Metalloproteinase-1/genetics
KW - Biomarkers
KW - Aorta
KW - Female
KW - Transforming Growth Factor beta/genetics
UR - http://www.scopus.com/inward/record.url?scp=85150687321&partnerID=8YFLogxK
U2 - 10.1111/cen.14907
DO - 10.1111/cen.14907
M3 - Journal article
C2 - 36890688
SN - 0300-0664
VL - 99
SP - 545
EP - 551
JO - Clinical Endocrinology
JF - Clinical Endocrinology
IS - 6
ER -