The role of a common TNNT2 polymorphism in cardiac hypertrophy.
We found a five-basepair insertion/deletion polymorphism in intron 3 of TNNT2, one of the genes responsible for hypertrophic cardiomyopathy. These five bases may be part of an intronic polypyrimidine tract sequence that may affect splicing. The purpose of the study was to examine the association of the polymorphism with cardiac hypertrophy. The study population consisted of 151 subjects with prominent concentric left ventricular hypertrophy, and 987 healthy subjects recruited from medical checkups (control population). The deletion/deletion genotype tended to be associated with a larger left ventricular mass/height ratio in the HCM population ( p<0.0001). Multiple regression analyses indicated that the left ventricular mass/height ratio was determined ( p<0.0001, R=0.738) by the TNNT2 genotype. Moreover, the frequency of the deletion allele was significantly higher in the hypertrophy population than in the control population ( p<0.0001). In vitro expression study revealed the deletion allele significantly affected the mRNA expression pattern by skipping exon 4 during splicing. In conclusion, TNNT2 deletion allele could be associated with a predisposition to prominent left ventricular hypertrophy.
Komamura
Kazuo
K
Department of Cardiovascular Dynamics, Research Institute, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita 565-8565, Japan. kkoma@hsp.ncvc.go.jp.
Iwai
Naoharu
N
Department of Epidemiology, Research Institute, National Cardiovascular Center, Suita, Japan.
Kokame
Koichi
K
Department of Vascular Physiology, Research Institute, National Cardiovascular Center, Suita, Japan.
Yasumura
Yoshio
Y
Department of Cardiology, National Cardiovascular Center, Suita, Japan.
Kim
Jiyoong
J
Department of Cardiology, National Cardiovascular Center, Suita, Japan.
Yamagishi
Masakazu
M
Department of Cardiology, National Cardiovascular Center, Suita, Japan.
Morisaki
Takayuki
T
Department of Bioscience, Research Institute, National Cardiovascular Center, Suita, Japan.
Kimura
Akinori
A
Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Tomoike
Hitonobu
H
Department of Cardiology, National Cardiovascular Center, Suita, Japan.
Kitakaze
Masafumi
M
Department of Cardiology, National Cardiovascular Center, Suita, Japan.
Miyatake
Kunio
K
Department of Cardiology, National Cardiovascular Center, Suita, Japan.
D000368:Aged; D000483:Alleles; D001483:Base Sequence; D004247:DNA / Q000737:chemistry; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics*; D007438:Introns; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D011110:Polymorphism, Genetic; D012326:RNA Splicing; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020107:Troponin T / Q000235:genetics*
D020107:Troponin T; D004247:DNA