Ethnicity African American

Race/ ethnicity (African Americans, Hispanic/ Latino Americans, American Indians, and some Asian Americans)... 

Corticosteroids and CIs can impair glucose control in previously diabetic patients, as well as cause new-onset post-transplant diabetes mellitus (PTDM) in 4% to 20% of patients. Corticosteroids induce insulin resistance and impair peripheral glucose uptake, whereas CIs appear to inhibit insulin production. " TAC seems to be more diabetogenic than CSA, although recent studies have failed to show a statistical difference." " Other possible risk factors that have been identified for PTDM include ethnicity (African-American or Hispanic), age (>40 years), pretransplant diabetes status, family history, and weight. " ... 

The prevalence of hypertension differs based on age, sex, and ethnicity. As individuals become older, their risk of high blood pressure increases. Individuals 55 years of age who do not have hypertension are estimated to have a lifetime risk of 90% of eventually developing hypertension. The National Health and Nutrition Examination Survey from 1999 to 2000 indicated that hypertension is slightly more prevalent in men (30.1%) than women (27.1%). However, the prevalence increased by 5.6% in women and has remained unchanged in men from 1988 to 2000.5 Hypertension prevalence is highest in African-Americans when compared to non-Hispanic whites and Mexican-Americans.1... 

Heart failure is more prevalent and associated with a worse prognosis in African-Americans compared to the general population.1 Unfortunately, deficiencies in disease prevention, detection, and access to treatment are well documented in minority populations. African-Americans and other races are underrepresented in clinical trials, compromising the extrapolation of results from these studies to ethnic subpopulations. The influence of race on efficacy and safety of medications used in HF treatment has received additional attention with... 

Non-modifiable risk factors include age, gender, race/ ethnicity, and heredity. Ischemic stroke risk is increased in those greater than 55 years of age, in men, and in African-Americans, Hispanics, and Asian-Pacific Islanders. It is also increased in those with a family history of stroke. Modifiable risk factors include a number of treatable disease states and lifestyle factors that can greatly influence overall stroke risk. Hypertension is... 

Race or ethnicity (Native American, Latino/Hispanic-American, Asian-American, African-American, and Pacific Islanders)... 

Over 66.8 million people worldwide have glaucoma, making it the second leading cause of blindness worldwide.1 In the United States it is estimated that 2.22 million people are affected by POAG, and by 2020 this number will increase to 3.36 million. The prevalence varies with race and ethnicity and it is 3 to 5 times more prevalent in African-Americans than Caucasians. The prevalence of POAG increases with age and is rarely seen in patients less than 40 years of age.2-4... 

Ethnicity Caucasian Caucasian Caucasian African-American, Asians, Hispanics Most common in Caucasians, rare in dark-skinned people Most common in African descendants... 

Chiu et al, 1992 Lin Finder, 1983 Lin et al, 1988b Potkin et al, 1984 Lin etal., 1989 Ruiz et al, 1996 Jann et al, 1989 Jann etal, 1992 Zhang-Wong etal., 1998). The majority of these studies were carried out with haloperidol. A number of studies examined differences between Caucasians and Hispanics, and African Americans and Caucasians (Midha et al., 1988b Midha etal, 1988a Ruiz et al., 1996). In general these studies provided mixed results. Another noteworthy feature of the research literature is that there appear to be no studies that have considered ethnic differences in pharmacokinetics and response for the depot antipsychotics. This may be an artifact of the low levels of depot prescribing found in the US, China, and Japan. 

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. 

Wagner etal. (1998) investigated the ethnic differences in antidepressant response to fluoxetine or placebo in 118 depressed, predominantly male, HIVpositive patients (White n = 79, Hispanic n = 17, African American n = 22). Nine Hispanic subjects (53%) dropped out of treatment making the results difficult to interpret. Among completers in the placebo arm, 80% (four out of five) of Hispanic subjects were responders as compared to 36% of African American subjects and 43% of White subjects. 

A pooled analysis of 14 875 adults (Hispanic, n = 361 White, n = 10 108 African American, n = 547 Asian, n = 112) who participated in 104 double-blind, placebo-controlled paroxetine trials for mood and anxiety disorders was performed to ascertain minority group differences (Roy-Byrne et al., 2005). There were significant differences in rates of response by ethnicity (p = 0.014) with the odds of responding being lower for the Asian and Hispanic subjects compared to the African American and White subjects. There was also a higher placebo response rate in Hispanic subjects. Rapidity of response and emergence of adverse effects were similar across groups. 

Identifying inter-ethnic variations in psychotropic response in African Americans and other ethnic minorities... 

The United States is becoming more diverse, ethnically and culturally. This process is happening primarily through immigration and also to some extent from differential birth rates ofvarious ethnic groups. Over a third of today s Americans are considered ethnic minorities. Currently Hispanics and African Americans each make up about 15% of the population. It is anticipated that individuals of European ancestry will become less than a majority in 2050 (US Census, 2000). 

Subsequently the medication was approved for self identified African Americans by the Federal Drug Administration (FDA), the first time a medication was approved for a specific racial group (US Food and Drug Administration, 2005). This combination was then marketed as BiDil. The approval led to a great deal of controversy and discussion, much of it critical, about the FDA decision. The findings from these trials, however, provide evidence that ethnicity can make a difference in clinical treatment response (Sankar 8c Kahn, 2005). 

Research in psychopharmacology has shown that ethnicity must be considered in psychiatry as well (Lawson, 1986 Pi 8c Simpson, 2005). Early clinical trials with antipsychotic and antidepressant medications showed that ethnic minorities may respond when given the same doses as Caucasians, and may have more side effects (Lawson, 1986 Lawson, 1990). However, dosing cannot be used as a measure of appropriate pharmacotherapy because an extensive literature has shown that African Americans often receive higher doses of antipsychotics despite evidence of more side effects. 

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). 

Lithium presents yet another model of ethnic variation in side effects and response. It is well established that African Americans show a higher red blood cell (RBC) to plasma ratio of lithium concentration when compared to Asians and... 

The clinical significance of this ethnic difference for psychiatry was found later. A study examining lithium tolerability found more side effects in African American patients with high RBC/plasma ratio even when the lithium levels were in the therapeutic range (Strickland etal., 1995). It is not known whether African Americans require lower doses and will respond with lower plasma levels. We do know that African Americans with mood disorders are less likely to be prescribed lithium either as primary treatment or adjunctive therapy (Valenstein etal., 2006 Kilbourne 8c Pincus, 2006). It is unknown as to whether the lack of tolerability at usual therapeutic doses is a factor. 

The argument is often made that African Americans and other ethnic minorities do not participate in clinical trials because they do not want to. African Americans in particular were thought to be suspicious of participation because of previous experiences of exploitation and manhandling of vulnerable minority groups (Melfi et al, 2000 Corbie-Smith et al, 1999). The Tusgekee syphilis study is often cited as a reason for mistrust (Shavers et al, 2000 Shavers et al, 2002 Corbie-Smith et al, 1999). This study was a federally funded study of the long-term consequences of syphilis on African American men initially started before antibiotics were available. 

Lanphear et al. (1996a, 1996b, 1997, 1998b) studied factors affecting PbB levels in urban children and found the following independent predictors of children s PbB levels dust lead loading in homes, African-American race/ethnicity, soil lead levels, ingestion of soil or dirt, lead content and condition of painted... 

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... 

Very few studies have focused on ethnic African groups. Therefore, very little is known about the molecular basis of ethnic differences in disease incidence and drug response in native Africans. Unfortunately, previous studies in African American subjects cannot be generalized to include native African populations, due to the great heterogeneity of racial ancestry of African American subjects, as well as other factors. 

Based on the population genotype-phenotype studies performed to date, assays for the molecular diagnosis of TPMT deficiency have focussed on alleles TPMT 2, TPMT 3A and TPMT 3C, as these represent 80-95% of all mutant alleles of this gene in Caucasians [46, 50]. However, the frequency and pattern of mutant alleles of this gene is different among various ethnic populations. For example, Southwest Asians (Indian, Pakistani) have a lower frequency of mutant TPMT alleles and all mutant alleles identified to date are TPMT 3A (Table 24.1) [52]. This is in contrast to Kenyans and Ghanaians where the frequency of mutant alleles is similar to Caucasians, and all mutant alleles are TPMT 3C (Table 24.1) [53, 54]. Among African Americans, TPMT 3C is the most prevalent allele, but TPMT 2... 

The presence of TPMTk3A alleles in the African American population is consistent with the genetic mixing that has been identified through historical and molecular analysis [12, 27]. These data, compared with that of different ethnic populations, reveal that the pattern of variant TPMT alleles differs significantly be-... 

Deficiency of thiopurine S-methyl transferase (TPMT) is another phenotype that exhibits inter-ethnic differences in frequency. TPMT is an enzyme that catalyzes methylation of therapeutic agents used in the treatment of acute lymphoblastic leukemia, rheumatoid arthritis, and autoimmune/inflammatory diseases, as well as in organ transplantation. Patients who have TPMT deficiency experience less efficient methylation and are at greater risk of fatal toxicity when treated with standard doses of fhiopurines. TPMT phenotype is defined by erythrocyte 6-mercapto-purine methylation. African American populations exhibit a 20% lower erythrocyte TPMT than Caucasian Americans, and persons of Chinese descent tend to exhibit greater activity than either of these other American subpopulations. 

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