Genetic analysis of the rhabdomyolysis-associated genes in forensic autopsy cases of methamphetamine abusers.
Methamphetamine (MA) use sometimes causes rhabdomyolysis, which has been associated with mortality. We analyzed potential rhabdomyolysis-susceptibility genes from autopsy samples of 18 methamphetamine abusers. We examined mutations in the ryanodine receptor 1 (RYR 1), carnitine palmitoyltransferase II (CPT II), very long-chain acyl-CoA dehydrogenase (VLCAD), and cytochrome P450 (CYP) 2D6 genes. Different RYR1 mutations that caused amino acid substitutions ((612)Ala>Thr and (4295)Ala>Val) were identified in 2 cases. In the CPT II gene, there was a new mutation ((545)Glu>Ala) in 1 case and there were mutations that did not change activity in 17 cases. In the VLCAD gene, there were mutations that did not change activity in 6 cases. In the CYP2D6 gene, homozygosity for CYP2D6∗10, which is associated with significantly reduced metabolic activity, was found in 3 cases, while 2 cases carried a different previously unreported missense mutation ((344)Arg>Gln and (48)His>Tyr). RYR1 mutations and the new CPT II mutation identified in this study were not observed in a control group. Eighteen cases that were genetically analyzed were also investigated immunohistochemically to diagnose the possibility of rhabdomyolysis. However, there were no significant mutations that reduced enzyme activity in the suspected cases of rhabdomyolysis. These data suggested no obvious relationship between the genetic mutations observed in this study and rhabdomyolysis.
Matsusue
Aya
A
Department of Forensic Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. miyoshi@fukuoka-u.ac.jp
Hara
Kenji
K
Kashiwagi
Masayuki
M
Kageura
Mitsuyoshi
M
Sugimura
Tomoko
T
Kubo
Shin-ichi
S
D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000235:genetics; D000328:Adult; D001344:Autopsy; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D005260:Female; D053803:Forensic Genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007564:Japan; D008297:Male; D008694:Methamphetamine / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012206:Rhabdomyolysis / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics
D019837:Ryanodine Receptor Calcium Release Channel; D008694:Methamphetamine; D019389:Cytochrome P-450 CYP2D6; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002334:Carnitine O-Palmitoyltransferase