title: Coronary risk in relation to genetic variation in MEOX2 and TCF15 in a Flemish population.
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.
authors.affiliation: Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Kapucijnenvoer 35, Box 7001, BE-3000, Leuven, Belgium. wenyi.yang@med.kuleuven.be.
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Yang
authors.affiliation: Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Kapucijnenvoer 35, Box 7001, BE-3000, Leuven, Belgium. thibault.petit@med.kuleuven.be.|Cardiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium. thibault.petit@med.kuleuven.be.
authors.forename: Thibault
authors.initials: T
authors.lastname: Petit
authors.affiliation: Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Kapucijnenvoer 35, Box 7001, BE-3000, Leuven, Belgium. lutgarde.thijs@med.kuleuven.be.
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Thijs
authors.affiliation: Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Kapucijnenvoer 35, Box 7001, BE-3000, Leuven, Belgium. zhenyu.yang@med.kuleuven.be.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Kapucijnenvoer 35, Box 7001, BE-3000, Leuven, Belgium. lotte.jacobs@med.kuleuven.be.
authors.forename: Lotte
authors.initials: L
authors.lastname: Jacobs
authors.affiliation: Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Kapucijnenvoer 35, Box 7001, BE-3000, Leuven, Belgium. aszussa@gmail.com.
authors.forename: Azusa
authors.initials: A
authors.lastname: Hara
authors.affiliation: Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Kapucijnenvoer 35, Box 7001, BE-3000, Leuven, Belgium. fangfei.wei@med.kuleuven.be.
authors.forename: Fang-Fei
authors.initials: FF
authors.lastname: Wei
authors.affiliation: Genomics and Bioinformatics Platform at Filarete Foundation, Department of Health Sciences and Graduate School of Nephrology, Division of Nephrology, San Paolo Hospital, University of Milan, Milan, Italy. erika.salvi@unimi.it.
authors.forename: Erika
authors.initials: E
authors.lastname: Salvi
authors.affiliation: Division of Nephrology and Dialysis, IRCCS San Raffaele Scientific Institute, University Vita-Salute San Raffaele, Milan, Italy. citterio.lorena@hsr.it.
authors.forename: Lorena
authors.initials: L
authors.lastname: Citterio
authors.affiliation: Division of Nephrology and Dialysis, IRCCS San Raffaele Scientific Institute, University Vita-Salute San Raffaele, Milan, Italy. simona.dellicarpini@hsr.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Delli Carpini
authors.affiliation: Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Kapucijnenvoer 35, Box 7001, BE-3000, Leuven, Belgium. yumei.Gu@med.kuleuven.be.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Gu
authors.affiliation: Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Kapucijnenvoer 35, Box 7001, BE-3000, Leuven, Belgium. Judita.Knez@med.kuleuven.be.
authors.forename: Judita
authors.initials: J
authors.lastname: Knez
authors.affiliation: Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Kapucijnenvoer 35, Box 7001, BE-3000, Leuven, Belgium. nicholas.cauwenberghs@student.kuleuven.be.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Cauwenberghs
authors.affiliation: Genomics and Bioinformatics Platform at Filarete Foundation, Department of Health Sciences and Graduate School of Nephrology, Division of Nephrology, San Paolo Hospital, University of Milan, Milan, Italy. matteo.barcella@unimi.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Barcella
authors.affiliation: Genomics and Bioinformatics Platform at Filarete Foundation, Department of Health Sciences and Graduate School of Nephrology, Division of Nephrology, San Paolo Hospital, University of Milan, Milan, Italy. cristina.barlassina@unimi.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Barlassina
authors.affiliation: School of Nephrology, University Vita-Salute San Raffaele, Milan, Italy. manunta.paolo@hsr.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Manunta
authors.affiliation: Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium. giulia.coppiello@gmail.com.
authors.forename: Giulia
authors.initials: G
authors.lastname: Coppiello
authors.affiliation: Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium. xlaranguren@unav.es.
authors.forename: Xabier L
authors.initials: XL
authors.lastname: Aranguren
authors.affiliation: Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Kapucijnenvoer 35, Box 7001, BE-3000, Leuven, Belgium. tatiana.kouznetsova@med.kuleuven.be.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kuznetsova
authors.affiliation: Genomics and Bioinformatics Platform at Filarete Foundation, Department of Health Sciences and Graduate School of Nephrology, Division of Nephrology, San Paolo Hospital, University of Milan, Milan, Italy. daniele.cusi@unimi.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Cusi
authors.affiliation: Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium. peter.verhamme@uzleuven.be.
authors.forename: Peter
authors.initials: P
authors.lastname: Verhamme
authors.affiliation: Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium. aernout.luttun@med.kuleuven.be.
authors.forename: Aernout
authors.initials: A
authors.lastname: Luttun
authors.affiliation: Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Kapucijnenvoer 35, Box 7001, BE-3000, Leuven, Belgium. jan.staessen@med.kuleuven.be.|R & D VitaK Group, Maastricht University, Maastricht, The Netherlands. jan.staessen@med.kuleuven.be.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Staessen
mesh_terms: D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001530:Belgium / Q000453:epidemiology; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; C484193:MEOX2 protein, human; C513109:TCF15 protein, human