| Budget Amount *help |
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
|
|---|
| Research Abstract |
Cardiomyopathy (CM) is one of the causes of cardiac sudden death (CSD). Mutations in nine genes that encode proteins of the cardiac sarcomere, such as cardiac β-myoshin heavy chain (MYH7), cardiac troponin T (TNNT2), cardiac troponin I (TNNI3) or cardiac myosin-binding protein C (MYBPC3), are identified as causes of CM. In the present study, mutations in MYH7, TNNT2, TNNI3 and MYBPC3 genes were analyzed among 23 cases of CSD caused by CM, 12 hypertrophic cardiomyopathy (HCM), 10 dilated cardiomyopathy (DCM), one arrhythrmogenic right ventricular cardiomyopathy (ARVC), with informed consent obtained from family members and 18 healthy individuals as control. The possibility of the genetic screening of CSD caused by CM was also examined. Genomic DNA was extracted using Quick Gene-800 (FUJIFILM, Japan). Exon 3-40 of MYH7, exon 2-16 of TNNT2, exon 1-8 of TNNI3 and exon 2-35 of MYBPC3 were amplified from genomic DNA by using primers designed from intron sequences. The sequencing analysis was done using BigDye Terminator v3. 1 Cycle Sequencing Kit (Applied Biosystems), and the PCR products were electrophoresed by ABI PRISM 310 Genetic Analyzer. Sequencing data were analyzed by running SeqScape Software ver. 2.5.0 (Applied Biosystems). In 23 CSD cases caused by CM, mutations were identified in 4 (33%) of 12 HCM and in 5 (50%) of 10 DCM. A total of 17 mutations was observed in 4 genes described above. The most frequently affected gene was MYH7 gene and mutations were identified in 5 (21.7%) of 23 CSD. Furthermore, a total of 17 single nucleotide polymorphisms was identified and there was significant difference between CM and control in MYBPC3 at position exon 21 +89. From these result% it was indicated that the genetic screening of the etiology gene of CM was applicable to the cause of death investigation in the endogenous sudden death cases.
|
