2 research outputs found
Investigation of the mechanisms mediating genetic susceptibility to cardiovascular disease on chromosomes 9p21 and 2q24
- Publication venue
- Publication date
- 01/01/2011
- Field of study
Recent genome-wide studies have identified novel loci associated with cardiovascular diseases, but the mechanisms mediating these associations are unknown. Investigation of intermediate phenotypes can identify the pathways involved and potential targets for therapeutic intervention. This study investigated the relationship with intermediate phenotypes at risk loci on chromosome 9p21 and 2q24. Chromosome 9p21 polymorphisms are associated with coronary artery disease and congenital intracranial aneurysms. In the present study risk variants were not associated with traditional risk factors, inflammatory mediators, carotid artery intimamedia thickness, echocardiographic measures of cardiac structure and function, or congenital heart defects. There was no evidence of copy number variation using MLPA. To identify genes involved in mediating disease susceptibility this study examined the association of chromosome 9p21 variants with peripheral blood expression in healthy subjects of three neighbouring genes: two cyclin-dependent kinase inhibitors, CDKN2A and CDKN2B, and a non-coding RNA of unknown function, ANRIL. Novel methodology combining allelic expression data from multiple transcribed markers was more powerful than total expression analysis for mapping cis-acting effects. Multiple loci were independently associated with expression of each gene, suggesting that several sites may modulate disease susceptibility. Disease-associated variants were all associated with allelic expression of ANRIL, while association with the other two genes was only detectable for some risk variants. Variants had an inverse effect on ANRIL and CDKN2B expression, supporting a role of antisense transcription in CDKN2B regulation. This study suggests that modulation of ANRIL expression mediates susceptibility to several important human diseases. Chromosome 2q24 polymorphisms were associated with hypertension in a study involving an Amish population; in vitro experiments suggested that influences on STK39 expression might mediate these effects. In the present study allelic expression analysis confirmed that reported SNPs were associated with STK39 expression in vivo, but were not associated with blood pressure in a large British cohort.EThOS - Electronic Theses Online ServiceBritish Cardiovascular Society : Swire Newcastle Healthcare Charity : British Heart FoundationGBUnited Kingdo
Drug monographs
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- Papatsonis
- Papoff
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- Pappert
- Paradisis
- Paradisis
- Paradisis
- Parisi
- Parke
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- Pasternak
- Patel
- Patel
- Patole
- Paul
- Paul
- Payne
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- Perry
- Perry
- Pershad
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- Peter
- Petersen
- Petersen
- Petersen
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- Phrommintikul
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- Pilgrim
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- Pilwoz
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- Plan
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- Plaud
- Playfor
- Playfor
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- Pokela
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- Purcell
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- Quarteman
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- Radloff
- Rahman
- Rahman
- Rahman
- Rahman
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- Ramaekers
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- Rankin
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- Rosenblatt
- Rosenfeld
- Rosenfeld
- Rossignol
- Rossignol
- Rossignol
- Roth
- Rothman
- Rouse
- Rouse
- Rowe
- Roy
- Royal College of Obstetricians and Gynaecologists
- Rozance
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- Rötig
- Saarenmaa
- Saarenmaa
- Saez-Lorens
- Sagirli
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- SEAQUAMAT Trial Group
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- Shah
- Shah
- Shah
- Shah
- Shah
- Shah
- Shama
- ShangGuan
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- Smith
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- Stacpoole
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- Strehle
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- Su
- Su
- Su
- Subhani
- Sullins
- Sullivan
- Sullivan
- SUMMIT Trial Study Group
- Suomalainen
- Suormala
- SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network
- Surridge
- Sury
- Suyagh
- Suyagh
- Swan
- Sweet
- Sweet
- Sweetman
- SYROCOT (Systematic Review on Congenital Toxoplasmosis) study group
- SYROCOT (Systematic Review on Congenital Toxoplasmosis) study group
- Szajewska
- Szilagi
- Sáez-Llorens
- Sørensen
- Tack
- Taddio
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- Tagbor
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- Taylor
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- Taylor
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- Taylor
- te Pas
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- Teo
- Terragna
- Tessin
- Tetzlaff
- Thayyil-Sudhan
- The Special Feed Working Group of the Paediatric Group of the British Dietetic Association
- Theilen
- Theilen
- Theis
- Thingvoll
- Thomas
- Thomas
- Thomas
- Thomas
- Thomas
- Thompson
- Thompson
- Thuy
- Tielsch
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- Tighe
- Timsit
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- Tookey
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- Toppare
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- Tsatsaris
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- Tubman
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- Tylki-Szymanska
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- Ugwamadu
- UK Group on Transmitted HIV Drug Resistance
- Urien
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- van den Anker
- van den Anker
- van den Broek
- van den Broek
- van den Broek
- van den Oever
- van der Burg
- van der Heide-Jalving
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- van Donselaar-van der Pant
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- van Lingen
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- van Rooij
- Van Rooij
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- Vandenplas
- Vandenplas
- Vandenplas
- Vanhatalo
- Vanier
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- Vargas
- Vargas-Origel
- Varner
- Vauzelle-Kervroëdan
- Veldman
- Veldman
- Vellodi
- Venkatesh
- Venkatesh
- Venkatesh
- Venkatesh
- Venter
- Vermes
- Vesikari
- Vestergaard
- Veuvonen
- Victorin
- Villain
- Villanueva-GarcĂa
- Vincent
- Viscardi
- Viscardi
- Vitali
- von Kries
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- Wardle
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- Wardle
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- Whitelaw
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- Whitfield
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- Wilby
- Wilcken
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- Willmore
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- Wilmer
- Wilson
- Wilson
- Wirth
- Withington
- Wolf
- Wolf
- Wolf
- Wolfe
- Wong
- Woo
- Woodrow
- Worldwide Atosiban versus Beta-agonists Study Group
- Wraith
- Wraith
- Wren
- Wright
- Wright
- Wu
- Wurthwein
- Wyckoff
- Wyckoff
- Wyllie
- Wyllie
- Wynn
- Xie
- Xinias
- Yalaz
- Yanni
- Yaseen
- Yates
- Yeh
- Yeh
- Yeung
- Yoshida
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- Young
- Young
- Young
- Yukawa
- YĂĽksel
- Zakrzewska-Bode
- Zaman
- Zanetti
- Zar
- Zeidan
- Zelicof-Paul
- Zelnik
- Zempleni
- Zeng
- Zhanel
- Zhang
- Zhao
- Ziaei
- Zuppa
- Publication venue
- 'Wiley'
- Publication date
- Field of study