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• Catecholamine levels were measured in serum from autopsy cases. • The MAOA -uVNTR polymorphism was associated with serum adrenaline levels in females. • The MAOA -uVNTR polymorphism was associated with serum dopamine levels in females. • The MAOA -uVNTR polymorphism was not associated with serum noradrenaline levels in females. • The MAOA -uVNTR polymorphism was not associated with serum catecholamine levels in males. Monoamine oxidase A (MAOA) catalyzes oxidative deamination of catecholamines. A functional variable number tandem repeat (VNTR) polymorphism in the promoter region of the MAOA gene has been previously reported. In the present study, we measured serum adrenaline (Adr), noradrenaline (Nad), and dopamine (DA) levels in 90 male and 34 female Japanese autopsy cases in which amphetamines or psychotropic drugs were not detected. We examined the frequencies of MAOA -uVNTR alleles in these cases and investigated the effects of the MAOA -uVNTR polymorphism on serum Adr, Nad, and DA levels. Evaluation indicated no significant association between MAOA -uVNTR polymorphism and serum Adr, Nad, or DA levels in males, although a significant association between MAOA -uVNTR polymorphism and serum Adr and DA levels were observed in females. Females with the 3/3 genotype had higher serum Adr and DA levels than those with a 4-repeat allele (3/4 and 4/4 genotypes) (p = 0.048 and 0.020, respectively). There was no significant association between MAOA -uVNTR polymorphism and serum Nad levels in females. The present study indicates that MAOA -uVNTR polymorphism influences serum Adr and DA levels only in females. [ABSTRACT FROM AUTHOR]

Japan is surrounded by the sea and is also a mountainous country with many rivers. Japan has the second- highest rate of deaths caused by drowning in the world. Pleural effusion (PE) is one of the major findings at autopsy. It is found in approximately 80% of drowning mortalities and is observable for a relatively long postmortem interval (PMI). We focused on the amount of pleural fluid in drowning cases, discussed the relationship of PE with the drowning environment, water temperature, and postmortem interval, and established more simple and practical criteria for the diagnosis of drowning. We measured the weight of the lungs, PE, and their sum as the intrathoracic (IT) weight (total weight of lungs + pleural effusion), and calculated the PE ratio [(PE weight/IT weight) × 100]. A total of 130 drowning deaths diagnosed through forensic autopsies were investigated in this study. The cases were classified by drowning environment (freshwater, brackish water, and seawater), water temperature (under 20 °C, more than 20 °C), and postmortem interval (less than 1 day, 1–3 days, more than 3 days). The present study demonstrated that the PE ratio may be more effective for the diagnosis of drowning. Moreover, the accumulation of PE is affected by drowning environment, water temperature, and PMI. Collectively, it is important to assess the PE ratio and consider these factors in autopsy cases of victims found in water. [ABSTRACT FROM AUTHOR]

Methamphetamine (MA) is an illicit stimulant that affects the central nervous system. Cytochrome P450 2D6 (CYP2D6) plays an important role in MA metabolism. Numerous allelic variants confer substantial variation in CYP2D6 activity among individuals. In the present study, we examined the frequencies of CYP2D6 alleles, including CYP2D6*1, *2, *4, *5, *10, *14A, *14B, *18, and *36, and multiplication, in 82 forensic autopsy cases of MA abusers and 567 autopsy cases in which MA was not detected (controls). Ultrarapid metabolizer (UM), extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM) phenotypes were predicted from CYP2D6 genotypes. Of MA abusers, 64 subjects were predicted to be EM, 17 were IM, and 1 was UM. No MA abuser had the predicted PM phenotype. No significant differences in CYP2D6 phenotype frequencies were found between MA abusers and controls. MA and amphetamine (AMP) concentrations were measured in the right heart blood, left heart blood, peripheral external iliac blood, urine, pericardial fluid, and bone marrow of MA abusers. MA concentrations in urine and bone marrow were significantly higher in IM than in EM. AMP concentration was not associated with CYP2D6 phenotype in any body fluid. These results suggest that the MA concentration in body fluids is influenced by CYP2D6 phenotypes in the Japanese population. [ABSTRACT FROM AUTHOR]

The article reports that according to research studies no association has been found between cardiac ion channel variants and sudden infant death. Recent molecular autopsy studies have although identified arrhythmia and inherited metabolic disease as possible cause of SUD and that small number of cases were due to disease-causing gene variants.

Abstract: In this study, five single nucleotide polymorphisms (SNPs) in the ABCC4, FBN1, CEP152, ZNF804B, and GALNT11 genes were investigated to assess allele frequencies in 14 different populations by a novel pentaplex PCR method. All SNPs were polymorphic in East Asians, whereas mutant alleles were absent or rare in non-East Asians. The frequencies of a mutant allele in FBN1 (rs140598) showed a north–south downward cline in East Asia, whereas those of a mutant allele in ZNF804B (rs1916830) were relatively uniform in East Asia. The highest frequencies of mutant alleles in ABCC4 (rs3765534), CEP152 (rs2289178), and GALNT11 (rs3778922) were observed in Okinawa. The mutant allele in GALNT11 was found only in Far-East Asian populations: the frequencies were about 0.153 in Okinawa, 0.076 in the main island of Japan, and 0.017–0.004 in Korea. These five East Asian- and Japanese-specific SNPs would be useful markers for forensic individualization, in particular, as ancestry-informative markers. [Copyright &y& Elsevier]

It is sometimes necessary to determine whether a forensic biological sample came from a Japanese person. In this study, we developed a 60-locus SNP assay designed for the differentiation of Japanese people from other East Asians using entirely and nearly Japanese-specific alleles. This multiplex assay consisted of 6 independent PCR reactions followed by single nucleotide extension. The average number and standard deviation of Japanese-specific alleles possessed by an individual were 0.81 ± 0.93 in 108 Koreans from Seoul, 8.87 ± 2.89 in 103 Japanese from Tottori, 17.20 ± 3.80 in 88 Japanese from Okinawa, and 0 in 220 Han Chinese from Wuxi and Changsha. The Koreans had 0–4 Japanese-specific alleles per individual, whereas the Japanese had 4–26 Japanese-specific alleles. Almost all Japanese were distinguished from the Koreans and other people by the factorial correspondence and principal component analyses. The Snipper program was also useful to estimate the degree of Japaneseness. The method described here was successfully applied to the differentiation of Japanese from non-Japanese people in forensic cases. This Japanese-specific SNP assay was named Japaneseplex . [ABSTRACT FROM AUTHOR]

Based on a prospective case-control study of forensic autopsies, the causes of cocaine (COC)-related sudden death (SD) are cardiovascular events in 62.0% of cases, cerebrovascular events in 14.0%, and others. A forensic autopsy of a male in his early forties revealed subarachnoid hemorrhage (SAH) at the base of the brain. A cerebral arterial aneurysm was not detected even though hemorrhage was clearly observed in the anterior cerebral artery (ACA) bifurcation area. The brain weighed 1488 g and was edematous. We histopathologically examined the left-ACA, right-ACA, and anterior communicating artery (Acom). Thickening of the internal vessel wall was observed as a pathological change. The internal elastic lamina of the right-ACA, near the peripheral part of Acom, was meandered with a jagged appearance. A toxicology examination detected COC and its metabolites, particularly benzoylecgonin, in blood and urine samples. Therefore, the present case was regarded as a non-fatal intoxication case, but also a COC-related death. Ethanol was also detected, indicating that COC was taken in combination with alcohol. The cause of COC-related death in the present case was SAH. COC use is known to induce aneurysmal SAH; however, whether an aneurysm had formed in the present case was unclear. Meander, extension, and degeneration of the internal elastic lamina of the right-ACA were observed near the bifurcation from the Acom. This area corresponded macroscopically with that considered to be the bleeding point from the blood vessel. Therefore, the present case was diagnosed as COC-related SD. [ABSTRACT FROM AUTHOR]

Japanese-specific alleles are expected to be powerful markers for the differentiation of the Japanese from other people. In this study, three single nucleotide polymorphisms (SNPs) in the GALNT11, H19, and PLA2G12A genes were analyzed in 2396 DNA samples from 25 global populations, and the derived alleles suggested that Japanese-specific alleles exist on autosomes. To identify new Japanese-specific alleles, candidate SNPs obtained from the HapMap database were investigated using 875 DNA samples from nine populations. A total of 67 (nearly) Japanese-specific derived alleles were observed. Of them, 57 showed higher frequencies in the Ryukyuans, living in the southernmost part of the Japanese Archipelago, than in the Wajins living in mainland Japan, and 43 were also present in Koreans at low frequencies. Jomon skeletons excavated from Hokkaido, the northernmost island of Japan, showed higher frequencies of the three derived alleles in the GALNT11, H19, and PLA2G12A genes than the Ryukyuans, suggesting that most of the 57 derived alleles observed at the high frequencies in the Ryukyuans originated from the Jomon lineage. These novel markers will be useful in the field of forensics. [ABSTRACT FROM AUTHOR]

Abstract: A hypervariable short tandem repeat (STR) polymorphism in intron 7 of the human complement factor I gene (CFI) was investigated to estimate the mutation rate in Japanese samples and to test linkage disequilibrium (LD) with an STR in the fibrinogen alpha chain gene (FGA). The expected heterozygosity and the mutation rate of CFI were estimated to be 0.917 and 0.002, respectively. No LD was observed between CFI and FGA. CFI is a useful supplementary marker for forensic science. [Copyright &y& Elsevier]

SCN5A (sodium channel, voltage-gated, type V, alpha subunit) gene encodes the cardiac sodium channel, a member of the voltage-gated sodium channel family. SCN5A mutations have been associated with a variety of inherited arrhythmias, including long QT syndrome and Brugada syndrome. We report an autopsy case of sudden unexpected nocturnal death syndrome. A man in his thirties died at night while sleeping. At autopsy, no traumatic injury, disease or drug intake was observed as a possible cause of death. We examined mutations in the SCN5A gene and identified a heterozygous mutation causing an R1193Q amino acid substitution. It was reported that the R1193Q polymorphism in the SCN5A gene destabilizes channel inactivation and may be a risk factor for Brugada and long QT syndrome. It may be considered that the cause of death in this case was sudden cardiac death., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The drowning index (DI) was devised to diagnose drowning deaths, and is the weight ratio of the lungs and pleural effusion to the spleen. Among drowning (94 cases), mechanical asphyxia (47 cases), and acute cardiac (42 cases) deaths, within 2 weeks postmortem we compared six markers, the weight of each lung, pleural effusion weight, total weight of the lungs and pleural effusion, spleen weight, heart weight, and the DI. Statistical analysis revealed that the total weight was heavier, while spleen weight was lighter, and the DI was significantly larger in the drowning group (p<0.05). We examined the relation between the postmortem time and these markers. We divided 94 drowning cases into three groups according to the postmortem duration, group A (0-3 days; 43 cases), group B (3-7; 29 cases), and group C (7-14; 22 cases). The cut-off point of the DI was analyzed using the receiver operating characteristic (ROC) curve. As a result, the DI cut-off point was 14.1 in cases within two postmortem weeks. Drowning is still a difficult autopsy diagnosis, but in our experience, DI is a valuable indicator., ((c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Haplotypes and allele frequencies of 17 Y-chromosomal short tandem repeat (Y-STR) markers were examined using the AmpFlSTR Yfiler PCR Amplification Kit (Applied Biosystems) in a population sample of 1166 Japanese male volunteers in 6 prefectures: Miyagi, Yamagata, Osaka, Tottori, Fukuoka, and Okinawa. A total of 1058 haplotypes were observed from 1166 males, and the most common haplotype detected in 12 males had a frequency of 1.03% and the discrimination capacity was 0.907. The R(ST) analysis showed statistically significant differences between Okinawa and the other subpopulations.

Isoelectric focusing has revealed that human complement factor I (CFI) is controlled by two polymorphic alleles, CFI(*)A and CFI(*)B, and a few rare variant alleles. In this study the molecular basis of the CFI polymorphism was investigated in 174 Japanese. The CFI(*)A was divided into two suballeles, CFI(*)As (R201S) and CFI(*)Ah (R406H). CFI(*)Aj, a rare variant allele originating from CFI(*)Ah, had an additional mutation (R502L). The distribution of these three mutations and two registered SNPs was investigated in a total of 2,471 individuals in 20 populations from various areas, and six haplotypes were observed. Haplotype H3, which is characterized by CFI(*)As, was found only in Far East populations: the frequencies were about 0.03 in the main island of Japan and lower than 0.01 in Okinawa and Korea. Haplotype H5, characterized by CFI(*)Ah, prevailed almost exclusively in East Asians and was observed at the highest frequencies in southern Chinese Han and Thais. CFI(*)Ah must have arisen in a southeastern part of Asia and thereafter have spread to neighboring populations.