Abstract
Recent data provided strong evidence for the association of single nucleotide polymorphisms (SNPs) in the lymphotoxin-α (LTA) and galectin-2 (LGALS2) genes with myocardial infarction (MI) in a Japanese population. For populations of other genetic background, the relevance of these polymorphisms in the pathogenesis of MI remains controversial. We aimed to define the role of LTA and LGALS2 SNPs in two German MI populations with markedly different ascertainment strategies. Two different MI populations were studied. In the first population, MI patients were ascertained by a strong family history of MI (n = 1214). Controls were unrelated disease-free participants of the study (n = 1080). The second population included patients suffering from sporadic (nonfamilial) MI from the German KORA register (n = 607). The control group consisted of participants of the WHO MONICA survey in Germany (n = 1492). TaqMan assays were used to determine the genotypes of 4 SNPs in the LTA genomic region and 1 SNP in the LGALS2 gene. Single SNPs in both genomic regions as well as haplotypes in the LTA genomic region were tested for association in various models of inheritance. No association with MI could be found for any of the examined SNPs in the LTA genomic region and LGALS2 gene, or for haplotypes spanning the LTA genomic region. In two MI populations of European descent with markedly different ascertainment strategies, we were not able to identify a significant association of SNPs in the LTA genomic region or the LGALS2 gene with MI. These variants are unlikely to play a significant role in populations of European origin.
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Acknowledgment
We appreciate the invaluable contribution of participants of the German MI Family Study, KORA Register and WHO MONICA Survey. We gratefully acknowledge the excellent technical assistance of Martina Köhler, Josef Simon, and Michaela Vöstner. This study was supported by the Deutsche Forschungsgemeinschaft (He1921/9-1, Schu672/14-1), the National Genome Network (01GS0418 to Drs Schunkert, Erdmann, and Hengstenberg), The Ernst- and Berta-Grimmke-Stiftung (Drs. Hengstenberg and Schunkert), the Wilhelm-Vaillant-Stiftung (Drs. Hengstenberg, Schunkert), the Deutsche Stiftung für Herzforschung (Drs. Hengstenberg and Schunkert). The KORA group consists of H.E. Wichmann (speaker), H. Löwel, C. Meisinger, T. Illig, R. Holle, J. John and their coworkers who are responsible for the design and conduct of the KORA studies. The MONICA Augsburg Study was initiated and conducted by Ulrich Keil and coworkers. The KORA research platform (KORA: Cooperative Research in the Region of Augsburg) and the MONICA Augsburg studies (Monitoring trends and determinants on cardiovascular diseases) were initiated and financed by the GSF-National Research Centre for Environment and Health, which is funded by the German Federal Ministry of Education, Science, Research and Technology and by the State of Bavaria.
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Supplementary Fig. 1
LD structure of the LTA (A) and LGALS2 (B) genomic regions is displayed as pair-wise r2 in Caucasian population (CEPH) and combined Japanese (Tokyo) and Han Chinese population (JPN CHIN). For comparison of different LD patterns, exactly 45 kb are displayed for both regions. SNPs genotyped in this study as well as known genes (RefSeq) are described in the header of the LD maps (PPT 278 kb)
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Sedlacek, K., Neureuther, K., Mueller, J.C. et al. Lymphotoxin-α and galectin-2 SNPs are not associated with myocardial infarction in two different German populations. J Mol Med 85, 997–1004 (2007). https://doi.org/10.1007/s00109-007-0211-4
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DOI: https://doi.org/10.1007/s00109-007-0211-4