Melusin gene (ITGB1BP2) nucleotide variations study in hypertensive and cardiopathic patients.
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.
Palumbo
Valeria
V
Dipartimento di Genetica Biologia e Biochimica, Università di Torino, via Santena 19, Torino 10126, Italy.
Segat
Ludovica
L
Padovan
Lara
L
Amoroso
Antonio
A
Trimarco
Bruno
B
Izzo
Raffaele
R
Lembo
Giuseppe
G
Regitz-Zagrosek
Vera
V
Knoll
Ralph
R
Brancaccio
Mara
M
Tarone
Guido
G
Crovella
Sergio
S
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
D003598:Cytoskeletal Proteins; C492400:ITGB1BP2 protein, human; D009124:Muscle Proteins