In epidemiological studies, moderate alcohol consumption has been consistently associated with a reduced risk of myocardial infarction (MI). About half of Japanese show an extremely high sensitivity to alcohol (ethanol), which is due to a missense mutation from glutamic acid (Glu) to lysine (Lys) at codon 487 in an isoenzyme of aldehyde dehydrogenase (ALDH2) with a low Km. We obtained a preliminary result that subjects homozygous for the Lys 487 allele had higher risk for myocardial infarction. The purpose of the present study was to assess this hypothesis by employing a larger cohort of subjects with MI. The experimental group consisted of 342 male subjects with demonstrated MI who were selected randomly from our outpatient clinic. As controls, we employed 1,820 male subjects with no cardiovascular complications who were selected from the Suita Study. All subjects provided their written informed consent to participate in the genetic analyses. Subjects with MI were older and had higher body mass index, higher prevalence of diabetes mellitus, higher prevalence of smoking habit, higher prevalence of the Lys/Lys genotype (homozygous for Lys 487 allele), and lower high density lipoprotein (HDL) cholesterol level (HDL-C). The ALDH2 genotype affected the level of alcohol consumption, and HDL-C. Multiple logistic analyses indicated that the odds ratio of the Lys/Lys genotype to the Lys/Glu+Glu/Glu genotype was 1.56 (p=0.0359). Inclusion of HDL-C as one of the independent variables downplayed the importance of the ALDH2 genotype. This may indicate that the ALDH2 genotype affects MI via its effects on HDL-C. In conclusion, the ALDH2 Lys/Lys genotype is a risk factor for myocardial infarction in Japanese men due to its influence on HDL cholesterol level.

This study demonstrated that the risk of TOFR <0.9 after tracheal extubation after sugammadex remains as high as 9.4% in a clinical setting in which neuromuscular monitoring (objective or subjective) was not used. Our finding underscores the importance of neuromuscular monitoring even when sugammadex is used for antagonism of rocuronium-induced neuromuscular block.

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Excessive alcohol consumption is a potent risk factor for high blood pressure. About half of Japanese show an extremely high sensitivity to alcohol, which is due to a genetic deficiency in an isoenzyme of aldehydede-hydrogenase with a low Km (ALDH2). It is possible that the effects of alcohol consumption on blood pressure differ according to the ALDH2 genotype. The purpose of the present study was to assess the influence of the ALDH2 genotype on the pressor effects of alcohol. The influence of the ALDH2 genotype on blood pressure was investigated in a large cohort (4,000 subjects) representing the general population in Japan. The genotype was determined by the TaqMan method. The genotype was significantly associated with alcohol consumption, gamma-GTP level, and HDL cholesterol level in both males and females. The odds ratio for the presence of hypertension for the Glu/Glu genotype in comparison to other genotypes was 1.67 (p< 0.0001, odds ratio=1.37-2.08, 95% confidence interval) among males. In contrast, the ALDH2 genotype had no significant effects on blood pressure among females. To investigate whether the ALDH2 genotype affected the sensitivity to the pressor effects of alcohol, we analyzed the effects of the ALDH2 genotype (Lys/Lys+Lys/Glu=0, Glu/Glu=1) and the level of alcohol consumption on blood pressure values after adjusting for age and BMI (residuals after adjusting for age and BMI). Among males, while the level of alcohol consumption significantly affected systolic, diastolic and pulse pressure, no significant interaction was observed between the ALDH2 genotype and the level of alcohol consumption in determining blood pressure levels. These results suggest that the Glu/Glu genotype is a potent risk factor for hypertension among males mainly through its association with the level of alcohol consumption, and that the ALDH2 genotype does not affect the sensitivity to the pressor effects of alcohol.

Mutations in the proprotein convertase subtilisin/kexin 9 (PCSK9) gene have been reported in affected members of two families with autosomal dominant hypercholesterolemia. To investigate the effects of common variants in PCSK9 on the cholesterol level, we conducted an association study using a large cohort representing the general population in Japan (n=1,793). Direct sequencing in all of the exonic regions identified 21 polymorphisms. After consideration of linkage disequilibrium among these polymorphisms, we selected and genotyped nine polymorphisms by the TaqMan method. The intron 1/C(-161)T and exon 9/I474 V polymorphisms were associated with levels of total cholesterol (TC) [C(-161)T, P=0.0285; I474 V, P=0.0069] and low-density lipoprotein cholesterol (LDL-C) [C(-161)T, P=0.0257; I474 V, P=0.0007]. The distributions of these polymorphisms in subjects with miocardial infarction (MI) (n=649) were not different from those in the control population. These results provide the first evidence that common variants intron 1/C(-161)T and exon 9/I474 V in PCSK9 significantly affect TC and LDL-C levels in the general population in Japan.