title: Melusin gene (ITGB1BP2) nucleotide variations study in hypertensive and cardiopathic patients.
abstract: BACKGROUND
  Melusin is a muscle specific signaling protein, required for compensatory hypertrophy response in pressure-overloaded heart. The role of Melusin in heart function has been established both by loss and gain of function experiments in murine models. With the aim of verifying the hypothesis of a potential role of the Melusin encoding gene, ITGB1BP2, in the modification of the clinical phenotype of human cardiomyopathies, we screened the ITGB1BP2 gene looking for genetic variations possibly associated to the pathological phenotype in three selected groups of patients affected by hypertension and dilated or hypertrophic cardiomyopathy
  
  
  METHODS
  We analyzed ITGB1BP2 by direct sequencing of the 11 coding exons and intron flanking sequences in 928 subjects, including 656 hypertensive or cardiopathic patients and 272 healthy individuals.
  
  
  RESULTS
  Only three nucleotide variations were found in patients of three distinct families: a C>T missense substitution at position 37 of exon 1 causing an amino acid change from His-13 to Tyr in the protein primary sequence, a duplication (IVS6+12_18dupTTTTGAG) near the 5'donor splice site of intron 6, and a silent 843C>T substitution in exon 11.
  
  
  CONCLUSIONS
  The three variations of the ITGB1BP2 gene have been detected in families of patients affected either by hypertension or primary hypertrophic cardiomyopathy; however, a clear genotype/phenotype correlation was not evident. Preliminary functional results and bioinformatic analysis seem to exclude a role for IVS6+12_18dupTTTTGAG and 843C>T in affecting splicing mechanism.Our analysis revealed an extremely low number of variations in the ITGB1BP2 gene in nearly 1000 hypertensive/cardiopathic and healthy individuals, thus suggesting a high degree of conservation of the melusin gene within the populations analyzed.
authors.affiliation: Dipartimento di Genetica Biologia e Biochimica, Università di Torino, via Santena 19, Torino 10126, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Palumbo
authors.forename: Ludovica
authors.initials: L
authors.lastname: Segat
authors.forename: Lara
authors.initials: L
authors.lastname: Padovan
authors.forename: Antonio
authors.initials: A
authors.lastname: Amoroso
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
authors.forename: Raffaele
authors.initials: R
authors.lastname: Izzo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lembo
authors.forename: Vera
authors.initials: V
authors.lastname: Regitz-Zagrosek
authors.forename: Ralph
authors.initials: R
authors.lastname: Knoll
authors.forename: Mara
authors.initials: M
authors.lastname: Brancaccio
authors.forename: Guido
authors.initials: G
authors.lastname: Tarone
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
mesh_terms: D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA
chemical_list: D003598:Cytoskeletal Proteins; C492400:ITGB1BP2 protein, human; D009124:Muscle Proteins