title: Mutation of the phospholamban promoter associated with hypertrophic cardiomyopathy.
abstract: Phospholamban is an endogenous inhibitor of sarcoplasmic reticulum calcium ATPase and plays a prime role in cardiac contractility and relaxation. Phospholamban may be a candidate gene responsible for cardiomyopathy. We investigated genome sequence of phospholamban in patients with cardiomyopathy. PCR-based direct sequence was performed for the promoter region and the whole coding region of phospholamban in 87 hypertrophic, 10 dilated, and 2 restricted cardiomyopathic patients. We found a heterozygous single nucleotide transition from A to G at -77-bp upstream of the transcription start site in the phospholamban promoter region of one patient with familial hypertrophic cardiomyopathy. This nucleotide change was not found in 296 control subjects. Using neonatal rat cardiomyocytes, the mutation, -77A-->G, increased the phospholamban promoter activity. No nucleotide change in the phospholamban coding region was found in 99 patients with cardiomyopathy. We suspect that the mutation plays an important role in the development of hypertrophic cardiomyopathy.
authors.affiliation: Department of Pediatric Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, 162-8666, Tokyo, Japan. sminamis@med.yokohama-cu.ac.jp <sminamis@med.yokohama-cu.ac.jp>
authors.forename: Susumu
authors.initials: S
authors.lastname: Minamisawa
authors.forename: Yoji
authors.initials: Y
authors.lastname: Sato
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Tatsuguchi
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Fujino
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Imamura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Uetsuka
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Rumiko
authors.initials: R
authors.lastname: Matsuoka
mesh_terms: D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic; D051381:Rats; D015533:Transcriptional Activation; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D000099211:Phospholamban