title: The association between BMP4 gene polymorphism and its serum level with the incidence of LVH in hypertensive patients.
abstract: BACKGROUND
  Bone morphogenic proteins 4 (BMP4) is associated with cardiac remodeling under different conditions. However, the role of BMP4 and its gene polymorphism in the incidence of left ventricular hypertrophy (LVH) in hypertensive patients remains unknown.
  
  
  METHODS
  A total of 1265 patients diagnosed with essential hypertension (EH) were recruited. Patients were assigned to LVH+ (n = 420) and LVH- (n = 845) groups. serum BMP4 level was measured and two single nucleotide polymorphism (SNPs) polymorphisms, 6007C > T and -5826G > A of BMP4 gene were genotyped. We also inhibited the BMP4 by small interfering RNA (siRNA). The effect of BMP4 on the hypertrophic response in Human Cardiomyocytes AC16 cells was studied.
  
  
  RESULTS
  We found that the 6007C > T polymorphism of the BMP4 gene and the serum BMP4 level were significantly associated with the risk to develop LVH. With TT as reference, multivariate logistic regression analysis showed the 6007CC genotype carriers had a higher susceptibility to LVH incidence (adjusted OR = 2.65, 95% CI: 1.63-4.31, adjusted P < 0.001). Our in vitro study shows that the BMP4 inhibition in cardiomyocyte by si-RNA technique significantly decreased the Ang II induced cardiomyocyte size and protein content per cell, indicating the importance of BMP4 in the cardiomyocyte hypertrophy.
  
  
  CONCLUSIONS
  Collectively, our data suggest that both the 6007C > T of the BMP4 gene and the serum BMP4 level may be used as potential marker for LVH incidence among the EH patients.
authors.affiliation: Department of cardiovascular diseases, Jiangyin Hospital of traditional Chinese medicine affiliated Nanjing University of Chinese Medicine, Jiangyin, 214400, Jiangsu, China. sh_gugl@126.com.
authors.forename: G L
authors.initials: GL
authors.lastname: Gu
authors.affiliation: Department of cardiovascular diseases, Wuxi Hospital of traditional Chinese medicine, Jiangyin, 214400, Jiangsu, China. ligongzi12@tom.com.
authors.forename: Q Y
authors.initials: QY
authors.lastname: Yang
authors.affiliation: Department of cardiovascular diseases, The People's Hospital of Jiangyin, Jiangyin, 214400, Jiangsu, China. dr_sun1@tom.com.
authors.forename: R L
authors.initials: RL
authors.lastname: Zeng
authors.affiliation: Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai, 214400, PR China. dr_sas@tom.com.
authors.forename: X L
authors.initials: XL
authors.lastname: Xu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D002097:C-Reactive Protein / Q000378:metabolism; D055316:Cystatin C / Q000097:blood; D000075222:Essential Hypertension; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000235:genetics; D017379:Hypertrophy, Left Ventricular / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011347:Procollagen / Q000097:blood; D014176:Protein Biosynthesis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D055316:Cystatin C; D010446:Peptide Fragments; D011347:Procollagen; D034741:RNA, Small Interfering; C041876:procollagen Type III-N-terminal peptide; D000804:Angiotensin II; D002097:C-Reactive Protein