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

Research output: Contribution to journalArticle

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 [electronic resource]
Volume16
Issue number1
DOIs
Publication statusPublished - Oct 1 2015

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Coronary Disease
Population
Single Nucleotide Polymorphism
Haplotypes
Homozygote
Cardiomyopathies
Alleles
Myocardial Infarction
Heterozygote
Endothelial Cells
Smoking
Confidence Intervals
Lipids
Incidence
Genes

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Yang, W. Y., Petit, T., Thijs, L., Zhang, Z. Y., Jacobs, L., Hara, A., ... Staessen, J. A. (2015). Coronary risk in relation to genetic variation in MEOX2 and TCF15 in a Flemish population. BMC genetics [electronic resource], 16(1), [116]. https://doi.org/10.1186/s12863-015-0272-2

Coronary risk in relation to genetic variation in MEOX2 and TCF15 in a Flemish population. / Yang, Wen Yi; Petit, Thibault; Thijs, Lutgarde; Zhang, Zhen Yu; Jacobs, Lotte; Hara, Azusa; Wei, Fang Fei; Salvi, Erika; Citterio, Lorena; Delli Carpini, Simona; Gu, Yu Mei; Knez, Judita; Cauwenberghs, Nicholas; Barcella, Matteo; Barlassina, Cristina; Manunta, Paolo; Coppiello, Giulia; Aranguren, Xabier L.; Kuznetsova, Tatiana; Cusi, Daniele; Verhamme, Peter; Luttun, Aernout; Staessen, Jan A.

In: BMC genetics [electronic resource], Vol. 16, No. 1, 116, 01.10.2015.

Research output: Contribution to journalArticle

Yang, WY, Petit, T, Thijs, L, Zhang, ZY, Jacobs, L, Hara, A, Wei, FF, Salvi, E, Citterio, L, Delli Carpini, S, Gu, YM, Knez, J, Cauwenberghs, N, Barcella, M, Barlassina, C, Manunta, P, Coppiello, G, Aranguren, XL, Kuznetsova, T, Cusi, D, Verhamme, P, Luttun, A & Staessen, JA 2015, 'Coronary risk in relation to genetic variation in MEOX2 and TCF15 in a Flemish population', BMC genetics [electronic resource], vol. 16, no. 1, 116. https://doi.org/10.1186/s12863-015-0272-2
Yang, Wen Yi ; Petit, Thibault ; Thijs, Lutgarde ; Zhang, Zhen Yu ; Jacobs, Lotte ; Hara, Azusa ; Wei, Fang Fei ; Salvi, Erika ; Citterio, Lorena ; Delli Carpini, Simona ; Gu, Yu Mei ; Knez, Judita ; Cauwenberghs, Nicholas ; Barcella, Matteo ; Barlassina, Cristina ; Manunta, Paolo ; Coppiello, Giulia ; Aranguren, Xabier L. ; Kuznetsova, Tatiana ; Cusi, Daniele ; Verhamme, Peter ; Luttun, Aernout ; Staessen, Jan A. / Coronary risk in relation to genetic variation in MEOX2 and TCF15 in a Flemish population. In: BMC genetics [electronic resource]. 2015 ; Vol. 16, No. 1.
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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.",
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T1 - Coronary risk in relation to genetic variation in MEOX2 and TCF15 in a Flemish population

AU - Yang, Wen Yi

AU - Petit, Thibault

AU - Thijs, Lutgarde

AU - Zhang, Zhen Yu

AU - Jacobs, Lotte

AU - Hara, Azusa

AU - Wei, Fang Fei

AU - Salvi, Erika

AU - Citterio, Lorena

AU - Delli Carpini, Simona

AU - Gu, Yu Mei

AU - Knez, Judita

AU - Cauwenberghs, Nicholas

AU - Barcella, Matteo

AU - Barlassina, Cristina

AU - Manunta, Paolo

AU - Coppiello, Giulia

AU - Aranguren, Xabier L.

AU - Kuznetsova, Tatiana

AU - Cusi, Daniele

AU - Verhamme, Peter

AU - Luttun, Aernout

AU - Staessen, Jan A.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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.

AB - 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.

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KW - Coronary heart disease

KW - MEOX2

KW - Population science

KW - TCF15

KW - Translational research

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