Objectives: It is well known that among hypertensive patients, an increased left ventricular mass (LVM) is a powerful predictor of cardiovascular morbidity and mortality. However, the mechanisms underlying LVM in hypertension are not completely understood, as the absolute value of blood pressure and other risk factors associated do not predict alone a definite LVM progression. Recently, the 9p21 chromosomal region has been consistently associated with coronary heart disease.
Methods and results: We examined the association of 384 single nucleotide polymorphisms (SNPs) in the short arm of chromosome 9 with LVM in 821 hypertensive individuals from northern Italy. We identified a SNP (rs894379) in the intronic region of the centlein, centrosomal protein (CNTLN) gene on chromosome 9p22, whose minor allele G is associated with an increased LVM. We performed a follow-up validation analysis for the top SNP in 1038 hypertensive individuals from southern Italy. We then combined the results and found a nominal association for rs894379 (β = 2.46, P = 0.0026).
Conclusion: We describe a new variant associated with echocardiography LVM. This result, though it needs to be further investigated, may improve our understanding of the genetic determination of this prognostically relevant trait.
aDepartment of Clinical Medicine and Prevention, San Gerardo Hospital, University of Milano-Bicocca, Milan, Italy
bBritish Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
cUnit of Genetics and Cardiovascular Research Institute, Istituto Ricovero Cura Carattere Scientifico ‘Multimedica’, Sesto San Giovanni
dConsortium for Human Molecular Genetics, University of Milano-Bicocca
eIstituto Auxologico Italiano IRCCS
fMilan Unit, Biomedical and Genetic Research Institute (IRGB), National Research Council of Italy, Milan
gDepartment of Neuroscience
hDepartment of Clinical Medicine and Cardiovascular and Immunological Sciences, Federico II University Hospital, Naples
iCardiology IV, Cardiothoracovascular Department A. De Gasperis, Niguarda Hospital, Milan, Italy
jDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK
Correspondence to Professor Giuseppe Mancia, Department of Clinical Medicine and Prevention, San Gerardo Hospital, University of Milano-Bicocca, Via Pergolesi 33, 20052 Monza, Italy. Tel: +39 039 233 3357; fax: +39 039 322 274; e-mail: firstname.lastname@example.org
Abbreviations: BP, blood pressure; BSA, body surface area; CNTLN, centlein centrosomal protein; ELN, elastin; ET-A, endothelin receptor type A; FC-ECG, cardiac frequency ECG; FDR, false discovery rate; GWAS, genome-wide association study; LVEDD, left ventricular end-diastolic diameter; LVM, left ventricular mass; LVMI, LVM index; LVH, left ventricular hypertrophy; MAF, minor allele frequency; MMP9, matrix metallopeptidase 9; SNP, single nucleotide polymorphism
Received 4 July, 2012
Accepted 13 July, 2012
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