Coronary risk in relation to genetic variation in MEOX2 and TCF15 in a Flemish population

Wen Yi Yang, Thibault Petit, Lutgarde Thijs, Zhen Yu Zhang, Lotte Jacobs, Azusa Hara, Fang Fei Wei, Erika Salvi, Lorena Citterio, Simona Delli Carpini, Yu Mei Gu, Judita Knez, Nicholas Cauwenberghs, Matteo Barcella, Cristina Barlassina, Paolo Manunta, Giulia Coppiello, Xabier L. Aranguren, Tatiana Kuznetsova, Daniele CusiPeter Verhamme, Aernout Luttun, Jan A. Staessen

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8 Citations (Scopus)

Abstract

Background: In mice MEOX2/TCF15 heterodimers are highly expressed in heart endothelial cells and are involved in the transcriptional regulation of lipid transport. In a general population, we investigated whether genetic variation in these genes predicted coronary heart disease (CHD). Results: In 2027 participants randomly recruited from a Flemish population (51.0 % women; mean age 43.6 years), we genotyped six SNPs in MEOX2 and four in TCF15. Over 15.2 years (median), CHD, myocardial infarction, coronary revascularisation and ischaemic cardiomyopathy occurred in 106, 53, 78 and 22 participants. For SNPs, we contrasted CHD risk in minor-allele heterozygotes and homozygotes (variant) vs. major-allele homozygotes (reference) and for haplotypes carriers (variant) vs. non-carriers. In multivariable-adjusted analyses with correction for multiple testing, CHD risk was associated with MEOX2 SNPs (P ≥ 0.049), but not with TCF15 SNPs (P ≤ 0.29). The MEOX2 GTCCGC haplotype (frequency 16.5 %) was associated with the sex- and age-standardised CHD incidence (5.26 vs. 3.03 events per 1000 person-years; P = 0.036); the multivariable-adjusted hazard ratio [HR] of CHD was 1.78 (95 % confidence interval, 1.25-2.56; P = 0.0054). For myocardial infarction, coronary revascularisation, and ischaemic cardiomyopathy, the corresponding HRs were 1.96 (1.16-3.31), 1.87 (1.20-2.91) and 3.16 (1.41-7.09), respectively. The MEOX2 GTCCGC haplotype significantly improved the prediction of CHD over and beyond traditional risk factors and was associated with similar population-attributable risk as smoking (18.7 % vs. 16.2 %). Conclusions: Genetic variation in MEOX2, but not TCF15, is a strong predictor of CHD. Further experimental studies should elucidate the underlying molecular mechanisms.

Original languageEnglish
Article number116
JournalBMC Genetics
Volume16
Issue number1
DOIs
Publication statusPublished - 2015 Oct 1

Keywords

  • Clinical genetics
  • Coronary heart disease
  • MEOX2
  • Population science
  • TCF15
  • Translational research

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Yang, W. Y., Petit, T., Thijs, L., Zhang, Z. Y., Jacobs, L., Hara, A., Wei, F. F., Salvi, E., Citterio, L., Delli Carpini, S., Gu, Y. M., Knez, J., Cauwenberghs, N., Barcella, M., Barlassina, C., Manunta, P., Coppiello, G., Aranguren, X. L., Kuznetsova, T., ... Staessen, J. A. (2015). Coronary risk in relation to genetic variation in MEOX2 and TCF15 in a Flemish population. BMC Genetics, 16(1), [116]. https://doi.org/10.1186/s12863-015-0272-2