Ethnicity Japanese

Although difficult to estimate, the prevalence of narcolepsy is between 0.03% and 0.06%.7 Significant differences have been reported for various ethnic groups. Narcolepsy has a higher prevalence in the Japanese and a lower prevalence in the Israeli populations.8,9 Cataplexy is not required for diagnosis however, between 50% and 80% of patients with narcolepsy have accompanying cataplexy.10... 

CYP2C19 is another example of the existence of both cross-ethnic and inter-individual variations in drug metabolism. This enzyme is involved in the metabolism of many psychotropics such as diazepam and tertiary tricyclic antidepressants, as well as one of the selective serotonin re-uptake inhibitors (SSRIs), citalopram. Using S-mephenytoin as the probe, previous studies showed that up to 20% of East Asians (Chinese, Japanese, and Koreans) are PMs, when only 3-5%... 

Recently, the presence of single nucleotide polymorphisms (SNPs) has been reported for several types of transporter. Extensive studies have been performed on the SNPs of OATP2 [100, 101], and the SNPs identified in African- and European-Americans are indicated in Fig. 12.3. Moreover, the frequency of SNPs differed among the African-American, European-Americans and Japanese, indicating the presence of an ethnic difference in the allelic mutation of this transporter [100, 101]. In addition, some of the mutations were associated with reduced transporter function and/or abnormalities in membrane targeting [100, 102] (Fig. 12.3). It is... 

Foreign clinical results are acceptable except in areas where there are immunological and ethnic differences between Japanese and foreigners. The ethnic factors are divided into two components intrinsic factors such as racial factors and physiological differences and extrinsic factors, which include cultural and environmental issues. In these cases, the MHLW may require that some bridging comparative clinical trials be performed with dose ranging protocols. This will enable absorption, distribution, metabolism, and excretion studies to be carried out on Japanese individuals and provide better dosage and indication for the Japanese people. The MHLW also requires that application be accompanied by one year of real-time stability data and that sterility test results be included. 

Important biological differences that potentially affect the metabolism of psychotropics have been described between Japanese and non-Asian children. For example, a pharmacogenetic ethnic difference was reported in cytochrome P450 (CYP) 2D6 metabolism of several antipsychotics and antidepressants, and in the CYP 2C19 metabolism of tricyclic agents. In adults, the rate of poor metabolizers of CYP 2D6 substrates is lower in Asians (about 1%) than in Caucasians (about 7%), while that of CYP 2C19 substrates is higher in Asians (15%-30%) than in Caucasians (3%-6%) (Poolsup et ah, 2000). Clinicians may need to keep these differences in mind when they use psychotropics in Japanese and other Asian patients, since such differences can lead to different behavioral responses or toxicity. 

As for the Block C (exons 2-5) haplotype IB, its significant associations with reduced AUC ratios and neutropenia were not clearly demonstrated, but a possible contribution under co-occurrence with haplotype 60 was suggested (38,47). In fact, the combinatorial haplotype 60 - IB increased bilirubin levels in healthy Japanese subjects (50). Because the frequency of IB homozygotes is rather low in Asians (39), further studies in other ethnic populations would clarify the role of 60- IB in irinotecan treatment. 

Miners et al. reported an ethnic difference in the His268Tyr (802 C>T) variant (99). In 91 Caucasians, the allele frequency for UGT2B7 2 (802 C>T) was 0.482 versus 0.268 for 84 Japanese subjects. Patel et al. reported a potential polymorphism in the ratio of (R)- and (iS )-oxazepam glucuronides in urine (100). While (J )-oxazepam is a substrate for UGT2B7, the turnover is very low and there was no difference between the UGT2B7 variants in terms of stereoselectivity (99). More recent data indicates that (.Sj-oxazepam is a UGT2B17 substrate. 

Ethnic groups were defined as follows Mongoloid, primarily Japanese descent Caucasoid, European descent Africoid, African descent. 

An apolipoprotein E variant is the only unequivocal genetic risk factor for late-onset Alzheimer s disease in a variety of ethnic groups. Caucasians and Japanese with the apo-E-s4 isoform have between 10 and 30 times the risk of developing Alzheimer s by 75 years of age. While the exact mechanism is unknown, evidence suggests an interaction with amyloid. Alzheimer s disease is characterised by plaques consisting of the peptide beta-amyloid. Apolipoprotein E enhances proteolytic breakdown of this peptide. However, the isoform apo-E-e4 is much less effective, which might result in an increased vulnerability to Alzheimer s in individuals with that gene variation. 

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