Individual ethnic difference

With respect to other ethnic groups, African Americans may have a differential sensitivity to weight gain on clozapine (de Leon etal, 2007). They may also require lower doses than Caucasians (Kelly et al, 2006) and inter-individual as well as ethnic responsiveness maybe partly explained by differences in dopamine receptor polymorphisms (Hwang et al, 2005). It is conceivable that side effects may also be differentially expressed based on pharmacodynamic differences resulting from polymorphisms in other receptor types (histaminergic, muscarinic, etc.). This area remains largely unexplored with respect to ethnic differences in antipsychotic side effects. 

Ethnic differences have been shown to influence response to psychotropic medications. Much of the focus on the explanation for such differences has been on drug-metabolizing (CYP) enzymes of the liver and their sway over pharmacokinetic factors. It is now well recognized that differences in the distribution of polymorphic variants of CYP enzymes exist between different ethnic groups. However, within ethnic groups there are considerable inter-individual variations in drug kinetics, which may not be accounted for solely by genetic variation. Responses to pharmacotherapy are multifaceted and involve the interaction of environmental and... 

Ethnic differences in CYP2D6 have been more thoroughly documented than with the other isoenzyme (Bradford, 2002). Over 70% of Caucasians but only about half of Asians, Sub-Saharan Africans, and African Americans have fully functional CYP2D6 alleles - alleles that code for normal metabolic activity. Approximately 50% of Asian and people of African ancestry have reduced function or nonfunctioning alleles. As a consequence, many older psychotropic medications are metabolized more slowly and plasma levels would be higher. Thus individuals of African and Asian ancestry would have an increased risk of side effects and should receive lower dose for a therapeutic response when compared to Caucasians of European descent (Lin, 2001 Lawson, 2000). 

McLeod HL, Syvanen A-C, Githang a J, Indalo A, Ismai D, Dewar K et al. Ethnic differences in catechol O-methyl-transferase pharmacogenetics frequency of the codon 108/158 low activity allele is lower in Kenyan than Caucasian or South-west Asian individuals. Pharmacogenetics 1998 8 195-199. 

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. 

McLeod HL, Pritchard SC, Githang a J et al. Ethnic differences in thiopurine methyltransferase pharmacogenetics evidence for allele specificity in Caucasian and Kenyan individuals. Pharmacogenetics 1999 9 773-776. 

Several authors have pointed out that the urinary excretion of hippurate is a poor indicator of exposure to toluene at 200 ppm [760 mg/m ] or lower (Jonai Sato, 1988 Too et al., 1991 Pierce et al., 1996). Therefore, data on ethnic differences in hippurate or cresol excretion in urine at these low exposure levels (e.g., Inoue et al., 1988) are of doubtful significance. Toluene level in expired air may be a more reliable parameter (Foo et al., 1991). Although at the level of the individual, data on urinary hippurate cannot be reliably used to estimate low toluene exposures, they can be used at the group level to establish whether at a certain location the toluene exposure remained below a particular threshold (Lauwerys, 1983). 

There are wide inter-ethnic differences. When cases are discovered the family should be investigated for low plasma cholinesterase activity and affected individuals warned. 

I Percentages of Individuals in Different Age, Gender, and Racial/Ethnic Groups Who Reported Cigarette Use in the Past Month, 2004... 

Rare individuals appear to be deficient metabolizers of nicotine. Individual differences are described both in the pattern and rates of nicotine metabolism. Ethnic differences in cotinine metabolism have also been observed. However, the enzymes responsible for nicotine metabolism and their genetic regulation have not been fully characterized. Understanding the basis for individual differences in nicotine kinetics and metabolism, and linking these differences to... 

Yuan HY, Chen JJ, Lee MT, etal. A novel functional VKORCl promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. Hum Mol Genet 2005 14(13) 1745-5L... 

The importance and clinical applicability of these measurements continue to evolve as there are probably racial and ethnic differences in the relationship between BMI, WC, and risk for development of disease and enhanced comorbidity. ° Table 140-3 outlines the current classification of overweight and obesity using BMI and WC. The table identifies risk for development of type 2 diabetes, hypertension, or cardiovascular disease at various stages of BMI or WC. Note that increased WC confers increased risk even in normal-weight individuals. 

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