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Human Molecular Genetics Advance Access originally published online on May 21, 2007
Human Molecular Genetics 2007 16(15):1821-1827; doi:10.1093/hmg/ddm130
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Association of variants in the BAT1-NFKBIL1-LTA genomic region with protection against myocardial infarction in Europeans

Werner Koch1,2,*, Petra Hoppmann1,2, Elena Michou1,2, Vanessa Jung1,2, Arne Pfeufer3,4, Jakob C. Mueller6, Christian Gieger5,7, H.-Erich Wichmann5,7, Thomas Meitinger3,4, Albert Schömig1,2 and Adnan Kastrati1,2

1 Deutsches Herzzentrum München, 80636 Munich, Germany, 2 1. Medizinische Klinik, 3 Institut für Humangenetik, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany, 4 Institut für Humangenetik, 5 Institut für Epidemiologie, GSF Forschungszentrum, 85764 Neuherberg, Germany, 6 Department of Behavioural Ecology and Evolutionary Genetics, Max Planck Institute for Ornithology, 82319 Starnberg (Seewiesen), Germany and 7 Lehrstuhl für Epidemiologie, Ludwig-Maximilians-Universität München, 81377 Munich, Germany

* To whom correspondence should be addressed at: Deutsches Herzzentrum München Lazarettstrasse 36, 80636 München Germany. Tel: +49 8912182601; Fax: +49 8912183053; Email: wkoch{at}dhm.mhn.de

Received February 22, 2007; Accepted May 10, 2007

Single-nucleotide polymorphisms within the BAT1-NFKBIL1-LTA genomic region (6p21.3) and the LGALS2 gene (22q13.1), encoding a regulator for lymphotoxin-{alpha}, the product of the LTA gene, have been reported to be linked with the risk of myocardial infarction in Japanese. We employed nine polymorphisms from the BAT1-NFKBIL1-LTA region and one polymorphism from the LGALS2 gene, and investigated whether such associations were also present in Europeans. The study included 3657 patients with myocardial infarction and 1211 control individuals with angiographically normal coronary arteries. Minor homozygous genotypes of polymorphisms in BAT1 (rs2239527, –23C/G), NFKBIL1 (rs2071592, –63T/A) and LTA (rs1800683, –162G/A; rs909253, 252G/A; rs1041981, Thr26Asn) were associated with moderately protective effects against myocardial infarction (P ≤ 0.045). The most abundant 9-marker haplotype of the BAT1-NFKBIL1-LTA region, named haplotype 1 (28% frequency in the study population), included the alleles of the five protective genotypes and was related with a significantly lower risk of myocardial infarction (OR 0.88, 95% CI 0.80–0.98; P = 0.015). Moreover, homozygosity for haplotype 1 was associated with an OR 0.72 (95% CI 0.57–0.90; P = 0.0047). Multiple logistic regression analysis revealed an independent protective effect against myocardial infarction in the homozygous carriers of haplotype 1 (adjusted OR 0.78, 95% CI 0.62–0.99; P = 0.043). A putative risk genotype of the polymorphism in the LGALS2 gene (rs7291467; 3279T/C) was not associated with myocardial infarction (OR 0.98, 95% CI 0.83–1.16; P = 0.84). Our finding that protective effects are linked with minor homozygous genotypes and haplotype 1 of the BAT1-NFKBIL1-LTA region in Europeans is opposite to the observation of associated risks in Japanese.


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