ArticlePLoS genetics2018
TIMP3 and TIMP1 are risk genes for bicuspid aortic valve and aortopathy in Turner syndrome.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
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Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.
- Turner Syndrome and the Thyroid Function-A Systematic and Critical Review.International journal of molecular sciences · 2024Pooled it
- Clinical practice guidelines for the care of girls and women with Turner syndrome.European journal of endocrinology · 2024Guideline
- Review
- Clinical and Genotypic Insights into Turner Syndrome: Emphasis on Cardiovascular Abnormalities.Journal of the ASEAN Federation of Endocrine Societies · 2025Article
- In Vivo Models of Cardiovascular Disease:Biomedicines · 2025Review
- Sex- and region-specific differences in microstructural remodeling and passive biomechanics of the aorta correlate with aneurysm propensity in a mouse model of severe Marfan syndrome.Acta biomaterialia · 2025Article
- Turner syndrome: the promise of fertility via stem cell technology.Hormones (Athens, Greece) · 2025Review
- Characterization of Turner Syndrome-associated Diabetes Mellitus.The Journal of clinical endocrinology and metabolism · 2025Article
- Identification of the Hub Gene LDB3 in Stanford Type A Aortic Dissection Based on Comprehensive Bioinformatics Analysis.Journal of cellular and molecular medicine · 2025Article
- Greater TIMP-1 protein levels and neointimal formation represent sex-dependent cellular events limiting aortic vessel expansion in female rats.IUBMB life · 2024Article
- Turner Syndrome where are we?Orphanet journal of rare diseases · 2024Review
- Heritable thoracic aortic disease: a literature review on genetic aortopathies and current surgical management.General thoracic and cardiovascular surgery · 2024Review
- Downregulation of LILRB4 Promotes Human Aortic Smooth Muscle Cell Contractile Phenotypic Switch and Apoptosis in Aortic Dissection.Cardiovascular toxicology · 2024Article
- Valvulopathies and Genetics: Where are We?Reviews in cardiovascular medicine · 2024Review
- Chromosomal Abnormalities of Interest in Turner Syndrome: An Update.Journal of pediatric genetics · 2023Review
- Coarctation of the Aorta: Modern Paradigms Across the Lifespan.Hypertension (Dallas, Tex. : 1979) · 2023Review
- Abnormal Left Ventricular Strain Correlates with Left Ventricular Dysfunction but not Aortic Pathology in Marfan Syndrome in Children.Pediatric cardiology · 2023Article
- Analysis of local extracellular matrix identifies different aetiologies behind bicuspid and tricuspid aortic valve degeneration and suggests therapies.Cellular and molecular life sciences : CMLS · 2023Article
- The multi-omic landscape of sex chromosome abnormalities: current status and future directions.Endocrine connections · 2023Review
- The Role of ADAMTS Proteoglycanases in Thoracic Aortic Disease.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Turner syndrome is caused by complete or partial loss of the second sex chromosome, occurring in ~1 in 2,000 female births. There is a greatly increased incidence of aortopathy of unknown etiology, including bicuspid aortic valve (BAV), thoracic aortic aneurysms, aortic dissection and rupture. We performed whole exome sequencing on 188 Turner syndrome participants from the National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Related Conditions (GenTAC). A gene-based burden test, the optimal sequence kernel association test (SKAT-O), was used to evaluate the data with BAV and aortic dimension z-scores as covariates. Genes on chromosome Xp were analyzed for the potential to contribute to aortopathy when hemizygous. Exome analysis revealed that TIMP3 was associated with indices of aortopathy at exome-wide significance (p = 2.27 x 10(-7)), which was replicated in a separate cohort. The analysis of Xp genes revealed that TIMP1, which is a functionally redundant paralogue of TIMP3, was hemizygous in >50% of our discovery cohort and that having only one copy of TIMP1 increased the odds of having aortopathy (OR = 9.76, 95% CI = 1.91-178.80, p = 0.029). The combinatorial effect of a single copy of TIMP1 and TIMP3 risk alleles further increased the risk for aortopathy (OR = 12.86, 95% CI = 2.57-99.39, p = 0.004). The products of genes encoding tissue inhibitors of matrix metalloproteinases (TIMPs) are involved in development of the aortic valve and protect tissue integrity of the aorta. We propose that the combination of X chromosome TIMP1 hemizygosity and variants of its autosomal paralogue TIMP3, significantly increases the risk of aortopathy in Turner syndrome.
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Registered trials
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