The variations of BOP gene in hypertrophic cardiomyopathy.
OBJECTIVE
The observation that Bop null allele mice show underdeveloped right ventricle and excessive development of left ventricle, suggests the possible relationship between human BOP gene and hypertrophic cardiomyopathy (HCMP). In our study, we investigated this possible relationship between BOP gene variations and QT dispersion, a noninvasive arrhythmic risk marker for HCMP.


METHODS
This cross-sectional study consisted of 50 patients clinically diagnosed with HCMP and 60 healthy subjects. Exonic regions of BOP gene were amplified by polymerase chain reaction and amplified exonic regions were analyzed by Single-Strand Conformation Polymorphisms (SSCP). The samples with different migration patterns were sequenced through an automated sequencing system. Continuous variables were compared by unpaired t-test for independent samples or Mann-Whitney U test. Genotype-disease relationship was tested by Chi-square test.


RESULTS
The nucleotide substitutions G275<or=A and C965<or=A in exon 2 and 7 were determined only in HCMP group. The G707<or=C, C710<or=T, T761<or=C, T1217<or=C SNPs in exon 6 and 9 are also found in the control group. Significant differences were found between two groups (p=0.002 and p=0.001). It was found that SNPs in exon 6 constitute a haplotype and that QT dispersion and corrected QT dispersion in the rare homozygote (707C/710T/761C) type carriers of HCMP patients for this haplotype were significantly lower than other genotypes (p=0.032 and p=0.030, respectively).


CONCLUSIONS
The human BOP gene was analyzed for the first time in HCMP to investigate possible association. The result that homozygosity of 707C/710T/761C haplotype is associated with lower QT dispersion and corrected QT dispersion supports the modifier role of BOP gene in HCMP.
Abaci
Neslihan
N
Department of Genetics, Research Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey. neslihanabaci@gmail.com
Güleç
Cağri
C
Bayrak
Fatih
F
Kömürcü Bayrak
Evrim
E
Kahveci
Gökhan
G
Erginel Unaltuna
Nihan
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D016827:CD8 Antigens / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002645:Chickens; D002891:Chromosomes, Human, Pair 21; D003430:Cross-Sectional Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D017548:Echocardiography, Transesophageal; D004569:Electroencephalography; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins; D012016:Reference Values; D014157:Transcription Factors / Q000235:genetics
C514383:BOP1 protein, human; D016827:CD8 Antigens; C477867:CD8beta antigen; D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; C484340:SMYD1 protein, human; D014157:Transcription Factors