Ethnic variability in the allelic distribution of pharmacogenes between Korean and other populations

Kim, In‐Wha; Kim, Kyung Im; Chang, Hyeu-jin; Yeon, Bong; Bang, Seojin; Park, Taesung; Kwon, Ji-sun; Kim, Sang Soo; Oh, Jung Mi

doi:10.1097/fpc.0b013e328358dd70

Cited by 9 publications

(4 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our interethnic comparison study for SNPs related to the body burden of heavy metals revealed that Koreans were genetically very similar to other East Asians, including Chinese and Japanese individuals but considerably different from Caucasian and African individuals. This result was consistent with the ethnic differences in previous studies on SNPs associated with asthma ( 17 ), pharmacogenesis ( 18 ), and autoimmunity ( 19 ), although direct comparison is impossible because the studied SNPs differed. The ethnic differences in SNPs are affected by genetic drift, migration, and natural selection, and verifying these differences will help us better understand the ethnic variations in disease susceptibility and phenotypes as well as complex genetic-environment interactions ( 20 ).…”

Section: Discussionsupporting

confidence: 91%

Allele Frequencies of the Single Nucleotide Polymorphisms Related to the Body Burden of Heavy Metals in the Korean Population and Their Ethnic Differences

et al. 2016

View full text Add to dashboard Cite

This study was performed to select single nucleotide polymorphisms (SNPs) related to the body burden of heavy metals in Koreans, to provide Korean allele frequencies of selected SNPs, and to assess the difference in allele frequencies with other ethnicities. The candidate-gene approach method and genome-wide association screening were used to select SNPs related to the body burden of heavy metals. Genotyping analysis of the final 192 SNPs selected was performed on 1,483 subjects using the VeraCode Goldengate assay. Allele frequencies differences and genetic differentiations between the Korean population and Chinese (CHB), Japanese (JPT), Caucasian (CEU), and African (YIR) populations were tested by Fisher’s exact test and fixation index (FST), respectively. The Korean population was genetically similar to the CHB and JPT populations (FST < 0.05, for all SNPs in both populations). However, a significant difference in the allele frequencies between the Korean and CEU and YIR populations were observed in 99 SNPs (60.7%) and 120 SNPs (73.6%), respectively. Ten (6.1%) and 26 (16.0%) SNPs had genetic differentiation (FST > 0.05) among the Korean-CEU and Korean-YIR comparisons, respectively. The SNP with the largest FST value between the Korean and African populations was cystathionine-β-synthase rs234709 (FST: KOR-YIR, 0.309; KOR-CEU, 0.064). Our study suggests that interethnic differences exist in SNPs associated with heavy metals of Koreans, and it should be considered in future studies that address ethnic differences in heavy-metal concentrations in the body and genetic susceptibility to the body burden of heavy metals.

show abstract

Section: Discussionsupporting

confidence: 91%

Allele Frequencies of the Single Nucleotide Polymorphisms Related to the Body Burden of Heavy Metals in the Korean Population and Their Ethnic Differences

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Levels and patterns of LD depend on a number of demographic factors such as population size and structure, population growth, admixture, migration and locus-specific factors such as mutation, selection, recombination, gene conversion and genetic drift [30,31]. The application and transferability of surrogate biomarkers and/or tagSNPs from a particular genome wide association study (GWAS) depends on the genetic relatedness between the studied populations [32][33][34][35]. Hence, it is important to know population-specific LD patterns among different genetic variants before widely implementing results of GWAS.…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity in the distribution of 159 drug-response related SNPs in world populations and their genetic relatedness

2020

View full text Add to dashboard Cite

Interethnic variability in drug response arises from genetic differences associated with drug metabolism, action and transport. These genetic variations can affect drug efficacy as well as cause adverse drug reactions (ADRs). We retrieved drug-response related single nucleotide polymorphism (SNP) associated data from databases and analyzed to elucidate population specific distribution of 159 drug-response related SNPs in twenty six populations belonging to five super-populations (African, Admixed Americans, East Asian, European and South Asian). Significant interpopulation differences exist in the minor (variant) allele frequencies (MAFs), linkage disequilibrium (LD) and haplotype distributions among these populations. 65 of the drug-response related alleles, which are considered as minor (variant) in global population, are present as the major alleles (frequency �0.5) in at least one or more populations. Populations that belong to the same super-population have similar distribution pattern for majority of the variant alleles. These drug response related variant allele frequencies and their pairwise LD measure (r 2) can clearly distinguish the populations in a way that correspond to the known evolutionary history of human and current geographic distributions, while D' cannot. The data presented here may aid in identifying drugs that are more appropriate and/or require pharmacogenetic testing in these populations. Our findings emphasize on the importance of distinct, ethnicity-specific clinical guidelines, especially for the African populations, to avoid ADRs and ensure effective drug treatment.

show abstract

“…In addition, Kim et al (2012) reported that JPT and CHB in Hapmap possess the common genetic information through MDS plot and Fst [ 32 ]. Therefore, we merged these two data into one East Asian data.…”

Section: Resultsmentioning

confidence: 99%

Analysis of Pharmacogenomic Variants Associated with Population Differentiation

et al. 2015

Self Cite

View full text Add to dashboard Cite

In the present study, we systematically investigated population differentiation of drug-related (DR) genes in order to identify common genetic features underlying population-specific responses to drugs. To do so, we used the International HapMap project release 27 Data and Pharmacogenomics Knowledge Base (PharmGKB) database. First, we compared four measures for assessing population differentiation: the chi-square test, the analysis of variance (ANOVA) F-test, Fst, and Nearest Shrunken Centroid Method (NSCM). Fst showed high sensitivity with stable specificity among varying sample sizes; thus, we selected Fst for determining population differentiation. Second, we divided DR genes from PharmGKB into two groups based on the degree of population differentiation as assessed by Fst: genes with a high level of differentiation (HD gene group) and genes with a low level of differentiation (LD gene group). Last, we conducted a gene ontology (GO) analysis and pathway analysis. Using all genes in the human genome as the background, the GO analysis and pathway analysis of the HD genes identified terms related to cell communication. “Cell communication” and “cell-cell signaling” had the lowest Benjamini-Hochberg’s q-values (0.0002 and 0.0006, respectively), and “drug binding” was highly enriched (16.51) despite its relatively high q-value (0.0142). Among the 17 genes related to cell communication identified in the HD gene group, five genes (STX4, PPARD, DCK, GRIK4, and DRD3) contained single nucleotide polymorphisms with Fst values greater than 0.5. Specifically, the Fst values for rs10871454, rs6922548, rs3775289, rs1954787, and rs167771 were 0.682, 0.620, 0.573, 0.531, and 0.510, respectively. In the analysis using DR genes as the background, the HD gene group contained six significant terms. Five were related to reproduction, and one was “Wnt signaling pathway,” which has been implicated in cancer. Our analysis suggests that the HD gene group from PharmGKB is associated with cell communication and drug binding.

show abstract

Ethnic variability in the allelic distribution of pharmacogenes between Korean and other populations

Cited by 9 publications

References 44 publications

Allele Frequencies of the Single Nucleotide Polymorphisms Related to the Body Burden of Heavy Metals in the Korean Population and Their Ethnic Differences

Allele Frequencies of the Single Nucleotide Polymorphisms Related to the Body Burden of Heavy Metals in the Korean Population and Their Ethnic Differences

Heterogeneity in the distribution of 159 drug-response related SNPs in world populations and their genetic relatedness

Analysis of Pharmacogenomic Variants Associated with Population Differentiation

Contact Info

Product

Resources

About