ArticleJournal of medical genetics2005
Linkage to the FOXC2 region of chromosome 16 for varicose veins in otherwise healthy, unselected sibling pairs.
Article in Journal of medical genetics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 71 citations in OpenAlex.
- Venocentric perspective on varicocele: summarizing mechanisms and explorations.Frontiers in physiology · 2026Review
- How Can Molecules Induce Hemorrhoids? The Role of Genetics and Epigenetics in Hemorrhoidal Disease.International journal of molecular sciences · 2025Review
- Article
- Glycocalyx disruption, endothelial dysfunction and vascular remodeling as underlying mechanisms and treatment targets of chronic venous disease.International angiology : a journal of the International Union of Angiology · 2024Review
- Molecular Determinants of Chronic Venous Disease: A Comprehensive Review.International journal of molecular sciences · 2023Review
- Digenic Inheritance of a FOXC2 Mutation and Two PIEZO1 Mutations Underlies Congenital Lymphedema in a Multigeneration Family.The American journal of medicine · 2022Article
- Role of mechanosignaling on pathology of varicose vein.Biophysical reviews · 2021Review
- Mechanisms of Lower Extremity Vein Dysfunction in Chronic Venous Disease and Implications in Management of Varicose Veins.Vessel plus · 2021Article
- Varicose veins of lower extremities: Insights from the first large-scale genetic study.PLoS genetics · 2019Article
- Global Expression Profiling Identifies a Novel Hyaluronan Synthases 2 Gene in the Pathogenesis of Lower Extremity Varicose Veins.Journal of clinical medicine · 2018Article
- Molecular Aspects of Wound Healing and the Rise of Venous Leg Ulceration: Omics Approaches to Enhance Knowledge and Aid Diagnostic Discovery.The Clinical biochemist. Reviews · 2017Review
- Matrix Metalloproteinases in Remodeling of Lower Extremity Veins and Chronic Venous Disease.Progress in molecular biology and translational science · 2017Review
- Biological findings from the PheWAS catalog: focus on connective tissue-related disorders (pelvic floor dysfunction, abdominal hernia, varicose veins and hemorrhoids).Human genetics · 2016Article
- A multicenter review of epidemiology and management of varicose veins for national guidance.Annals of medicine and surgery (2012) · 2016Article
- Segregated Foxc2, NFATc1 and Connexin expression at normal developing venous valves, and Connexin-specific differences in the valve phenotypes of Cx37, Cx43, and Cx47 knockout mice.Developmental biology · 2016Article
- Matrix Metalloproteinases as Regulators of Vein Structure and Function: Implications in Chronic Venous Disease.The Journal of pharmacology and experimental therapeutics · 2015Review
- Forkhead box C2 promoter variant c.-512C>T is associated with increased susceptibility to chronic venous diseases.PloS one · 2014Article
- Matrix metalloproteinases as potential targets in the venous dilation associated with varicose veins.Current drug targets · 2013Review
- Absence of venous valves in mice lacking Connexin37.Developmental biology · 2013Article
- Microcephaly, intellectual impairment, bilateral vesicoureteral reflux, distichiasis, and glomuvenous malformations associated with a 16q24.3 contiguous gene deletion and a Glomulin mutation.American journal of medical genetics. Part A · 2012Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe FOXC2 gene on 16q24 is mutated in lymphoedema distichiasis (LD), in which varicose veins (VV) are a common feature. We hypothesised that this gene might be implicated in the development of VV in the normal population, therefore, after performing a classical twin study, we tested for linkage and association in white women. We also tested for linkage with haemorrhoids (H), as a separate venous anomaly at the same locus.
methodsA total of 2060 complete female twin pairs aged 18-80 years from the St Thomas' Adult UK Twin registry replied to questions on VV and H as part of a broader postal survey of 6600 twins (62% response rate). Dizygotic female twin pairs were tested for linkage and association to the candidate marker D16S520 (1903 individuals genotyped), which is located about 80 kb from FOXC2.
resultsCasewise concordance rates were significantly higher for monozygotic than dizygotic twins for both phenotypes (VV 67% v 45%; p = 2.2x10(-6); H 68% v 59%; p = 0.01; H including during pregnancy 73% v 64%; p = 2.1x10(-4)), corresponding to additive genetic heritabilities in liability of 86% (95% confidence interval (CI) 73% to 99%) for VV and 56-61% for H (95% CI 43% to 73%). The presence of VV and H were significantly correlated. We found significant evidence of linkage to the marker for VV (MLS(ASP) = 1.37, p = 0.01; GLM(ASP/DSP) Z = 3.17 p = 0.002), but no association. Both linkage and association tests were negative for H. The combined phenotype of having VV and H did not show any evidence of linkage or association.
conclusionThese results demonstrate VV and H to be heritable, related conditions, and the data strongly suggest FOXC2 to be implicated in the development of VV in the general population.
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