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Dr Ann Walker

  • Telephone:

    0044 20 7679 6279

  • Extension:

    46279

  • Email:

    ann.walker@ucl.ac.uk

  • Address:

    305 Centre for Cardiovascular Genetics,
    BHF Laboratories, Rayne Building,
    London,
    WC1E 6JF

  • Appointments:

    Senior Lecturer in Medical Genetics, Centre for Cardiovascular Genetics, Institute of Cardiovascular Science

Research Summary

I am interested in the genetic regulation of iron and zinc, and interactions with lipid metabolism and inflammation, as potentially tractable determinants of cardiovascular health.

Iron and variants of iron-metabolic genes have been implicated by several lines of evidence in atherosclerosis and hypertension.  Genome wide association studies have consistently found associations with between specific variants of the gene encoding the iron regulatory protein HFE and risk factors for cardiovascular disease: red blood cell traits haemoglobin concentration and haematocrit, which may predispose to increased viscosity and blood pressure; increased blood pressure itself, and abnormalities of plasma lipid profiles.   Also, excess iron is deposited in atherosclerotic plaque and this may be implicated in progression of plaque macrophages to lipid-filled foam cells.  Iron homeostasis is also strongly regulated by inflammation.  Zinc transporter variants have been associated with blood pressure. Research is focussed on investigating the mechanisms underlying these associations, and the  identification of genetic sub-groups of patients in whom iron-related risk of cardiovascular disease may be treatable.

Putative mechanisms underlying the association of HFE variants with blood pressure will be investigated by testing associations with candidate intermediate traits, red blood cell and iron measures, lipid measures and blood viscosity.   These studies are collaborative, benefitting from large and well-characterised prospective observational study cohorts in the UCLEB Consortium. Cell culture studies of monocytic cells and primary monocyte-derived macrophage cells will be used to investigate the effect of HFE genotype and iron status upon lipid uptake and metabolism.  Studies are in development to investigate blood pressure and arrhythmias in haemochromatosis (hereditary iron overload) and controls according to iron load and HFE genotype, and to investigate the effects of iron supplementation in anaemic women upon measures of arterial structure and function and on blood pressure.


Research Activities

  • Cardiovascular Genetics
  • Genetic epidemiology of cardiovascular disease

Recent Publications

Displaying 42 most recent publications. For the full list please visit UCL Discovery

  1. Sewell GW,Hannun YA,Han X,Koster G,Bielawski J,Goss V,Smith PJ,Rahman FZ,Vega R,Bloom SL,Walker AP,Postle AD,Segal AW (2012) Lipidomic profiling in Crohn's disease: abnormalities in phosphatidylinositols, with preservation of ceramide, phosphatidylcholine and phosphatidylserine composition. Int J Biochem Cell Biol, 44(11), 1839 - 1846. 10.1016/j.biocel.2012.06.016.
  2. Walker AP,Fowkes RC,Saleh F,Kim SH,Wilkinson P,Cabrera-Sharp V,Talmud PJ,Humphries SE,Looijenga LH,Bouloux PM (2012) Genetic analysis of NR0B1 in congenital adrenal hypoplasia patients: identification of a rare regulatory variant resulting in congenital adrenal hypoplasia and hypogonadal hypogonadism without testicular carcinoma in situ. Sex Dev, 6(6), 284 - 291. 10.1159/000342295.
  3. Grewal R,Dooley JS,Latham K,Tavarozzi F,Wallis-Jones S,Gallagher L,Jeffery R,Walker AP (2012) MOLECULAR GENETIC TESTING FOR HFE MUTATIONS AS A DIAGNOSTIC AID AND THE FIRST STEP IN IDENTIFYING PATIENTS WITH UNEXPLAINED IRON OVERLOAD: A TEN YEAR EXPERIENCE AT ANTHONY NOLAN/ROYAL FREE HOSPITAL TISSUE ANTIGENS, 79(6), 587 - 587.
  4. Sewell GW,Rahman FZ,Levine AP,Jostins L,Smith PJ,Walker AP,Bloom SL,Segal AW,Smith AM (2012) Defective tumor necrosis factor release from Crohn's disease macrophages in response to Toll-like receptor activation: relationship to phenotype and genome-wide association susceptibility loci. Inflamm Bowel Dis, 18(11), 2120 - 2127. 10.1002/ibd.22952.
  5. Smith AM,Rahman FZ,Hayee B,Graham SJ,Marks DJ,Sewell GW,Palmer CD,Wilde J,Foxwell BM,Gloger IS,Sweeting T,Marsh M,Walker AP,Bloom SL,Segal AW (2009) Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease. J Exp Med, 206(9), 1883 - 1897. 10.1084/jem.20091233.
  6. Lim FL,Dooley JS,Roques AW,Grellier L,Dhillon AP,Walker AP (2008) Hepatic iron concentration, fibrosis and response to venesection associated with the A77D and V162del "loss of function" mutations in ferroportin disease. Blood Cells, Molecules, and Diseases, 40(3), 328 - 333.
  7. Ala A,Walker AP,Ashkan K,Dooley JS,Schilsky ML (2007) Wilson's disease The Lancet, 369, 397 - 408.
  8. Sebastiani G,Wallace DF,Davies SE,Kulhalli V,Walker AP,Dooley JS (2006) Fatty liver in H63D homozygotes with hyperferritinemia. World Journal of Gastroenterology, 12(11), 1788 - 1792.
  9. Walker AP (2005) Portal vein thrombosis: what is the role of genetics? European Journal of Gastroenterology and Hepatology, 17(7), 705 - 707.
  10. Walker AP,Partridge J,Srai SK,Dooley JS (2004) Hepcidin: what every gastroenterologist should know. Gut, 53(5), 624 - 627.
  11. Sebastiani G,Wallace DF,Lioumi M,Goutos I,Mitchell WA,Bomford AB,Dhillon AP,Dooley JS,Ragoussis J,Walker AP (2003) Non HFE-related haemochromatosis: exclusion of the 1q21 zinc- iron regulated transporter-like (ZIRTL) gene in juvenile haemochromatosis Journal of Hepatology, 38(3), 376 - 377. 10.1016/S0168-8278(02)00426-9.
  12. Devalia V,Carter K,Walker AP,Perkins SJ,Worwood M,May A,Dooley JS (2002) Autosomal dominant reticulo-endothelial iron overload associated with a three base pair deletion in the ferroportin 1 gene J HEPATOL, 36, 182 - 182.
  13. Cox T,Rochette J,Camaschella C,Walker A,Robson K (2002) Clinical haemochromatosis in HFE mutation carriers The Lancet, 360(9330), 412 - 414. 10.1016/S0140-6736(02)09582-X.
  14. Sebastiani G,Wallace DF,Licumi M,Mitchell WA,Goutos I,Bomford AB,Dooley JS,Ragoussis J,Walker AP (2002) Normal ZIRTL sequence in juvenile and neonatal haemochromatosis J HEPATOL, 36, 266 - 266.
  15. Wallace DF,Walker AP,Pietrangelo A,Clare M,Bomford AB,Dixon JL,Powell LW,Subramaniam VN,Dooley JS (2002) Frequency of the S65C mutation of HFE and iron overload in 309 subjects heterozygous for C282Y Journal of Hepatology, 36(4), 474 - 479. 10.1016/S0168-8278(01)00304-X.
  16. Sebastiani G,Wallace DF,Davies SE,Kulhalli V,Walker AP,Dooley JS (2002) Fatty liver and iron overload in H63D homozygotes J HEPATOL, 36, 266 - 266.
  17. Devalia V,Carter K,Walker AP,Perkins SJ,Worwood M,May A,Dooley JS (2002) Autosomal dominant reticulo-endothelial iron overload associated with a three base pair deletion in the ferroportin 1 gene (SLC11A3) Blood, 100, 695 - 697. 10.1182/blood-2001-11-0132.
  18. O'Toole D,Kelly EJ,McAllister MM,Layton AW,Norrdin RW,Russell WC,Saeb-Parsy K,Walker AP (2001) Hepatic failure and hemochromatosis of Salers and Salers-cross cattle Veterinary Pathology, 38(4), 372 - 389.
  19. Walker AP (2000) DMT1 expression: avoiding too much of a good thing Gut, 46(2), 151 - 152.
  20. Gu M,Cooper JM,Butler P,Walker AP,Mistry PK,Dooley JS,Schapira AHV (2000) Oxidative phosphorylation defects in Wilson's disease liver Hepatology, 32(4 Pt 2), 487A.
  21. Wallace DF,Walker AP,Pietrangelo A,Clare M,Bomford AB,Dooley JS (2000) The S65C mutation of HFE may contribute to iron overload in C282Y heterozygotes Hepatology, 32(4 Pt 2), 487A.
  22. Loke KY,Poh KSL,Walker AP,Tan JAMA,Tay AHN (2000) An atypical kindred with X-linked adrenal hypoplasia congenita, normal puberty, and normal Dax-1 promoter and coding sequence JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM, 13(1), 29 - 36.
  23. Wallace DF,Walker AP,Pietrangelo A,Clare M,Bomford AB,Dooley JS (2000) The S65C mutation of HFE may contribute to iron overload in C282Y heterozygotes J HEPATOL, 32, 135 - 135.
  24. Dooley JS,Walker AP (2000) Genetic hemochromatosis: detection, management, and population screening Genetic Testing, 4(2), 97 - 101.
  25. Gu M,Cooper JM,Butler P,Walker AP,Mistry PK,Dooley JS,Schapira AH (2000) Oxidative-phosphorylation defects in liver of patients with Wilson's disease The Lancet, 356(9228), 469 - 474.
  26. Walker AP,Wallace DF,Partridge J B,A B D,J S (1999) Atypical haemochromatosis: phenotypic spectrum and beta2-microglobulin candidate gene analysis. Journal of Medical Genetics, 36(7), 537 - 541.
  27. Merryweather-Clarke AT,Pointon JJ,Shearman JD,Robson KJ,Jouanolle AM,Mosser A,David V,Le Gall JY,Halsall DJ,Elsey TS,Kelly A,Cox TM,Clare M,Bomford A,Vandwalle JL,Rochette J,Borot N,Coppin H,Roth MP,Ryan E,Crowe J,Totaro A,Gasparini P,Roetto A,Camaschella C,Darke C,Wallace DF,Saeb-Parsy K,Dooley JS,Worwood M,Walker AP (1999) Polymorphism in intron 4 of HFE does not compromise haemochromatosis mutation results. The European Haemochromatosis Consortium. Nature Genetics, 23(3), 271 - 271.
  28. Wallace DF,Dooley JS,Walker AP (1999) A novel mutation of HFE explains the classical phenotype of genetic hemochromatosis in a C282Y heterozygote. Gastroenterology, 116(6), 1409 - 1412.
  29. Merryweather-Clarke AT,Shearman JD,Robson KJH,Pointon JJ,Liu Y-T,Bomford A,Dooley J,Walker AP,Worwood M (1998) Hemochromatosis-related mutation detection. Blood, 91, 2620 - 2621.
  30. Partridge J,Wallace DF,Robertson A,Fox MF,Simons JP,Dooley JS,Walker AP (1998) Cloning and molecular characterization of a cross-homologous zinc finger locus ZNF204. Genomics, 50, 116 - 118.
  31. Wallace DF,Partridge J,Robertson A,Simpson VM,Worwood M,Bomford AB,Volz A,Ziegler A,Dooley JS,Walker AP (1998) A 6p22 reference map of leukocyte DNA: exclusion of rearrangement in four cases of atypical haemochromatosis. Eur J Hum Genet, 6, 523 - 526.
  32. Wallace DF,Partridge J,Dooley JS,Walker AP (1998) Classical phenotype of genetic haemochromatosis in a Cys282Tyr heterozygote due to compound heterozygosity with a novel splice site mutation. HEPATOLOGY, 28(4), 526A - 526A.
  33. Partridge J,Wallace DF,Raja KB,Dooley JS,Walker AP (1998) Monocyte-macrophage ferric reductase activity is inhibited by iron and stimulated by cellular differentiation. Biochemical Journal, 336, 541 - 543.
  34. The_U K _Haemochromatosis_Consortium_Worwood M,Bowen DJ,Burnett AK,Jackson HA,Lawless S,Raha-Chowdhury R,Shearman JD,Wallace DF,Dooley JS,Partridge J,Walker AP,Bomford A,Rosenberg WMC,Merryweather-Clarke AT,Robson KJH,Pointon JJ (1998) H63D is a haemochromatosis-associated allele(Reply) Gut, 43, 441 - 442.
  35. Worwood M,Shearman JD,Wallace DF,Dooley JS,Merryweather-Clarke AT,Pointon JJ,Rosenberg WMC,Bowen DJ,Burnett AK,Jackson HA,Lawless S,Raha-Chowdhury R,Partridge J,Williams R,Bomford A,Walker AP,Robson KJHTUKHC (1997) A simple genetic test identifies 90% of UK patients with haemochromatosis Gut, 41, 841 - 844.
  36. Dooley JS,Walker AP,Macfarlane B,Worwood M (1997) Genetic haemochromatosis. Report of a meeting of physicians and scientists at the Royal Free Hospital School of Medicine The Lancet, 349, 1688 - 1693.
  37. Robson KJ,Shearman JD,Merryweather-Clarke AT,Pointon JJ,Rosenberg WM,Walker AP,Dooley JS,Bomford A,Raha-Chowdhury R,Worwood M (1997) Haemochromatosis: a gene at last? Journal of Medical Genetics, 34, 148 - 151.
  38. Walker AP,Muscatelli F,Stafford AN,Chelly J,Dahl N,Blomquist HK,Delanghe J,Willems PJ,Steinmann B,Monaco AP (1996) Mutations and phenotype in isolated glycerol kinase deficiency The American Journal of Human Genetics, 58(6), 1205 - 1211.
  39. Muscatelli F,Walker AP,De Plaen E,Stafford AN,Monaco AP (1995) Isolation and characterization of a MAGE gene family in the Xp21.3 region Proceedings of the National Academy of Sciences of the United States of America, 92(11), 4987 - 4991.
  40. Zanaria E,Muscatelli F,Bardoni B,Strom TM,Guioli S,Worley KA,Lalli E,Moser C,Walker AP,McCabe ERB,Meitinger T,Monaco AP,Sassone Corsi P,Camerino G (1994) An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita Nature, 372(6507), 635 - 641.
  41. Muscatelli F,Strom TM,Walker AP,Zanaria E,Récan D,Meindl A,Bardoni B,Guioli S,Zehetner G,Rabl W,Schwartz HP,Kaplan JC,Camerino G,Meitinger T,Monaco AP (1994) Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism Nature, 372(6507), 672 - 676.
  42. King SC,Stapleton PM,Walker AP,Love DR (1994) Two dinucleotide repeat polymorphisms at the DMD locus Human Molecular Genetics, 3(3), 523 - 523.

Qualifications

  • 1987: Doctor of Philosophy, University of London

Keywords

  • Arrhythmia
  • Atherosclerosis
  • Bioinformatics
  • Blood pressure
  • Cardiovascular Genetics
  • Haemochromatosis
  • Inflammation
  • Innate immunity
  • Metal ion homeostasis - iron, copper, zinc
  • Microarray analysis of mRNA expression
  • Phagocyte gene expression and signaling networks