Ethnicity allele frequency

The discrepancies between the results of studies in different ethnic groups may be partially due to differences in allele frequencies. 

The function of DMEs is also thought to include the detoxification of dietary products and the evolution of plant metabolites, including drugs [11]. The selective forces responsible for the maintenance of different alleles in different populations may include the fact that one allele may enable improved rates of implantation, improved prenatal growth and development, improved postnatal health in response to dietary or environmental selective pressures or improved resistance to bacteria, viruses or parasites [11, 14]. Allele frequencies may also reflect ethnic dietary differences that have evolved over thousands of years [15]. 

Tab. 24.1 TPMTgenotype and allele frequencies (%) in different ethnic populations. The relevant reference is shown in paretheses...

Fig. 24.3 Allele frequency of MDR1 C3435T polymorphism in different ethnic populations.

Ethnic variation in allele frequencies can lead to important differences in disease susceptibility, outcome and drug metabolism [68, 69]. In addition to single nucleotide polymorphisms, variable number of tandem repeat (VNTR) regions have been shown to have functional significance. 

Fig. 24.5 TSER allele frequencies in different ethnic groups.

Fig. 24.6 Mutant allele frequencies of SNPs in distinct ethnic populations. B2AR-/I2 adrenoreceptor, COMT-catechol-O-methyltransferase. Glu27 and TPMT 3C allele frequencies were used for the B2AR and TPMTgenes, respectively.

Considerable heterogeneity has been demonstrated with respect to average plasma Lp(a) levels in different ethnic groups. These differences cannot be entirely explained by differences in allele frequencies that exist between these groups [i.e., are not entirely due to allele-specific effects on Lp(a) concentrations] (M13, S3, S4). Interestingly, in the Sudanese population, Lp(a) levels are primarily (81%) determined by factors other than the size of the apo(a) allele, while in the Malay population, only 23% of the variation in Lp(a) levels could not be accounted for by size differences in the gene (S3). In Caucasians, it has previously been reported that 40-70% of the variance in Lp(a) levels can be... 

How do these data apply from one racial or ethnic group to another when there may be significant differences in allele frequencies between groups ... 

Significant ethnic variability is observed with many pharmacogenetic markers (38). Consequently, the demographics of the study population need to be taken into account when performing power analyses to determine the appropriate sample size. If the frequency of the polymorphism to be studied is unknown in any of the ethnic groups included in the study, the polymorphism should be screened in relevant population controls to determine their allele frequency. This will help to narrow down the number of polymorphisms to be included and prevent using finite patient DNA to assess markers that may have low frequency or be absent from the study population. 

Methylenetetrahydrofolate reductase is an approximately 19,301 base pair gene with 11 exons and located on chromosome lp36.3 (2). Multiple polymorphic sites have been described, with the C677T and A1298G most often studied. As expected, allele frequency data varies by ethnicity The MTHFR C677T variant allele is present in 34% of Caucasians, 20% of Italians and Hispanics, 14% of African-Americans, and <1 % of Africans (3,4). The MTHFR A1298G allele is present in n%-36% of Western Europeans (4). 

Allele frequencies appear to vary widely among diverse ethnic populations though only small numbers of subjects in a few populations have been reported (106). For example, allele frequencies for the Arg554Lys polymorphism range from 0.09 to 0.14 in Native American, French Canadian and Canadian Inuit subjects to 0.32 in subjects of Chinese descent to 0.40-0.57 in subjects of African descent. Limited information suggests that polymorphisms at codons 517 and 570 may be confined to subjects of African descent, but studies of larger populations are necessary to verify this. 

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. 

---