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 language | English |
|---|---|
| Article number | 116 |
| Journal | BMC genetics [electronic resource] |
| Volume | 16 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Oct 1 2015 |
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Keywords
- Clinical genetics
- Coronary heart disease
- MEOX2
- Population science
- TCF15
- Translational research
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
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 journal › Article
}
TY - JOUR
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.
KW - Clinical genetics
KW - Coronary heart disease
KW - MEOX2
KW - Population science
KW - TCF15
KW - Translational research
UR - http://www.scopus.com/inward/record.url?scp=84942575804&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84942575804&partnerID=8YFLogxK
U2 - 10.1186/s12863-015-0272-2
DO - 10.1186/s12863-015-0272-2
M3 - Article
AN - SCOPUS:84942575804
VL - 16
JO - BMC Genetics
JF - BMC Genetics
SN - 1471-2156
IS - 1
M1 - 116
ER -