Application of foreign clinical data across geographic regions can accelerate drug development. Drug disposition can be variable, and identification of factors influencing responsible pharmacokinetic/pharmacogenomic approaches could facilitate the universal application of foreign data and reduce the total amount of phase III clinical trials evaluating risks in different populations. Our objective was to establish and compare genotype (major cytochrome P450 (CYP) enzymes)/phenotype associations for Japanese (native and first- and third-generation Japanese living abroad), Caucasian, Chinese, and Korean populations using a standard drug panel. The mean metabolic ratios (MRs) for the four ethnic groups were similar except for a lower activity of CYP2D6 in Caucasians and CYP2C19 in Asians. Genotype, not ethnicity, impacted the MR for CYP2C9, CYP2C19, and CYP2D6; neither affected CYP1A2, CYP2E1, and CYP3A4/5 activities. We conclude that equivalent plasma drug concentrations and metabolic profiles can be expected for native Japanese, first- and third-generation Japanese, Koreans, and Chinese for compounds handled through these six CYP enzymes.

Objective: To investigate the personal features associated with dropout from regular outpatient care among persons with type 2 diabetes mellitus (DM).Methods: A total of 160 DM patients were enrolled in the study. As a retrospective analysis, outpatient's clinical characteristics, lifestyle, or social features were gathered from their medical records or interview sheets. All the subjects were divided into two groups by adherence to diabetic care, namely, 'dropout case' (DC) or 'ongoing case' (OC), and were subjected to comparative analysis. We called the patients who did not receive outpatient treatment from the clinic on a regular basis, including treatment from other clinics or dropout of diabetic care, as DC. In contrast, patients who regularly visited the clinic were defined as OC. An unconditional multiple logistic regression analysis was performed to analyze the association of adherence to diabetic care with several personal features.Results: Sixty-eight of 160 subjects (42.5%) were recognized as DC. The remaining 92 subjects (57.5%) were considered as OC. Young age (p=0.045), low plasma glucose (p=0.005) and hemoglobin A1c (HbA1c) levels (p=0.005), nonmedication (p<0.001) and no past history of DM (p=0.007) at the initial visit were the features related to dropout by crude analysis. Even after adjustment for age and gender by multivariate analysis, there remained significant inverse associations of dropout with HbA1c level, medical treatment (oral agents or insulin) and previous DM history. Neither occupation, distance from residence to clinic, smoking habit nor drinking habit was associated with dropout. Dropout mostly occurred after the initial or second visit.Conclusions: A mild condition of DM may be related to dropout from regular outpatient care. It may be necessary to clearly show the objectives and importance of regular visit to an outpatient clinic for diabetic care, particularly for screened mild DM cases in public health activities.

It has been reported that the mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism, also called NADH dehydrogenase subunit 2-237 methionine/ leucine (ND2-237 Met/Leu) polymorphism, may be associated with longevity in Japanese individuals, and that the mt5178A genotype may have an antiatherogenic influence. To determine whether mt5178 A/C polymorphism influences blood pressure, we genotyped 412 healthy Japanese individuals and performed a crosssectional study investigating the relationship between genotype and blood pressure. In women with mt5178A, the mean diastolic blood pressure was higher than in those with mt5178C by 3.2 mmHg (P ¼ 0.040). In men, no statistically significant difference in systolic or diastolic blood pressure was observed between mt5178 A/C genotypes. However, a significant correlation between mt5178 A/C genotypes and the effects of habitual drinking on blood pressure was found. After adjustment for several factors, in men carrying mt5178C, both systolic and diastolic blood pressure were significantly higher in daily drinkers than in occasional (P ¼ 0.002 and 0.002, respectively) as well as nondrinkers (Po0.001 and 0.001, respectively), whereas in men carrying mt5178A, no significant differences in blood pressure were detected, irrespective of alcohol consumption. These results suggest that mt5178 A/C ( ¼ ND2-237 Met/Leu) polymorphism may influence both diastolic blood pressure in Japanese women and the blood-pressureincreasing effect of drinking in Japanese men.

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Longevity-associated mitochondrial DNA 5178 A/C polymorphism may be associated with IOP in Japanese men.

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