J Mol Med (2004) 82:756–761 DOI 10.1007/s00109-004-0576-6 ORIGINAL ARTICLE Paul G. McGlinchey · Mark S. Spence · Chris C. Patterson · Adrian R. Allen · Gillian Murphy · David A. Savage · A. Peter Maxwell · Pascal P. McKeown Cytokine gene polymorphisms in ischaemic heart disease: investigation using family-based tests of association Received: 11 February 2004 / Accepted: 26 May 2004 / Published online: 18 September 2004  Springer-Verlag 2004 Abstract Atherosclerosis has an inflammatory basis, with cytokines, cellular adhesion molecules and pro-in- flammatory cells having important roles in the initiation and progression of this process. Interleukin (IL) 6, IL-10 and transforming growth factor (TGF) b 1 have been proposed as important modulators of the atherosclerotic process, with IL-6 having a pro-inflammatory, athero- genic effect and IL-10 and TGF-b 1 having anti-inflam- matory, protective roles. The possible role of functional polymorphisms in the promoter regions of the IL-6, IL-10 and TGF-b 1 genes in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population using two recently described family-based tests of association. We genotyped 1,012 individuals from 386 families with at least one member prematurely af- fected with IHD. Using the combined transmission dis- equilibrium test (TDT)/sib-TDT and the pedigree dis- equilibrium test, no association between any of the IL-6 174G/C, IL-10 1082G/A and TGF-b 1 509C/T poly- morphisms and IHD was found. Our data demonstrate that, in an Irish population, these polymorphisms are not associated with IHD. Keywords Ischaemic heart disease · Inflammation · Gene polymorphism · Interleukin 6 · Interleukin 10 · Transforming growth factor-b 1 Abbreviations IHD: Ischaemic heart disease · IL: Interleukin · PDT: Pedigree disequilibrium test · TDT: Transmission disequilibrium test Paul G. McGlinchey is a Specialist Registrar in Cardiology. He graduated MB, BCh, BAO from Queen’s Uni- versity, Belfast, UK, in 1995. He was awarded a MD degree in 2003, also from Queen’s University, Belfast, following submission of a thesis detailing 2 years of full-time research investigating the genetic basis of ischaemic heart disease us- ing family-based tests of asso- ciation. He has subsequently returned to clinical practice. Pascal McKeown is a Consultant Cardiologist/ Senior Lecturer in Cardiology at the Royal Victoria Hospital and Queen’s University, Bel- fast, UK. He graduated with his primary medical degree from Queen’s University, Belfast, in 1984 and was subsequently awarded the MD degree in 1991. He undertook further research training at the Max Planck Institute, Bad Nauheim, Germany, from 1994–1995. His research interests include the genetic and molecular basis of cardiac disease. P. G. McGlinchey · M. S. Spence · G. Murphy · P. P. McKeown Regional Medical Cardiology Centre, Royal Victoria Hospital, Grosvenor Road, Belfast, BT12 6BA, UK C. C. Patterson Department of Epidemiology and Public Health, Queen’s University of Belfast, Mulhouse Building, Grosvenor Road, Belfast, BT12 6BJ, UK A. R. Allen · P. P. McKeown ( ) ) Department of Medicine, Queen’s University of Belfast, Institute of Clinical Science, Grosvenor Road, Belfast, BT12 6BJ, UK e-mail: p.p.mckeown@qub.ac.uk Tel.: +44-28-90634825, Fax: +44-28-90312907 D. A. Savage Department of Medical Genetics, Queen’s University of Belfast, Belfast City Hospital, Lisburn Road, Belfast, BT9 7AB, UK A. P. Maxwell Department of Nephrology, Queen’s University of Belfast, Belfast City Hospital, Lisburn Road, Belfast, BT9 7AB, UK