Genetic Polymorphisms of Pharmacogenomic VIP Variants in the Circassian Subpopulation from Jordan

Background: It has been suggested that genetic variation within candidate pharmacogenes contributes to the differences in drug safety and efficacy as well as risk of adverse drug reactions among different ethnic groups. Illustrating the polymorphic distribution of Very Important Pharmacogenes (VIPs) in various ethnic groups will contribute to the development of personalized medicine for those populations. Objective: The present study aimed to identify the polymorphic distribution of VIPs in the Circassian subpopulation of Jordan and compare their allele frequencies with those of other populations. Methods: A total of 130 healthy and unrelated Circassian adults from Jordan were randomly recruited and genotyped for eleven VIP variants within the thiopurine S-methyltransferase (TPMT), ATP-binding cassette, sub-family B, member 1 (ABCB1), and vitamin D receptor (VDR) genes via Sequenom’s MassARRAY® genotyping platform (iPLEX GOLD). Results: Our data on the allelic frequencies of the investigated VIP variants were compared to those of 18 other populations, comprising 11 HapMap populations, 6 Exome Aggregation Consortium populations, and the Chechen- Jordanian population from Jordan. Circassian-Jordanians were found to most resemble the African, Chechen- Jordanian, European (Finnish), European (non-Finnish), and South-Asian populations. Conclusion: Circassians from Jordan significantly differ from other populations in terms of the allelic frequencies of selected VIP variants. The present findings constitute the first set of pharmacogenetic data for Circassian population from Jordan, providing a basis for safe drug administration that may be useful in diagnosing and treating diseases in this ethnic group.

LD scores are associated with differences in allele frequencies between populations but LD score regression can still distinguish confounding from polygenicity

SummaryThe LD score regression method tests whether there is an association between the LD score and allele frequency differences between cases and controls. It makes the assumption that there is no association between LD score and allele frequency differences between populations and hence that any observed association is due to a polygenic effect rather than population stratification. This assumption has not previously been tested. In comparisons between HapMap populations we observe that there is indeed an association between the LD score and allele frequency differences. However this effect is small and when we carry out simulations of large case-control samples the effect becomes negligible. We conclude that if the intercept is small then any increase in mean chi-squared does indeed reflect a polygenic effect rather than population stratification.

Allele and Genotype Distributions of DNA Repair Gene Polymorphisms in South Indian Healthy Population

Various DNA repair pathways protect the structural and chemical integrity of the human genome from environmental and endogenous threats. Polymorphisms of genes encoding the proteins involved in DNA repair have been found to be associated with cancer risk and chemotherapeutic response. In this study, we aim to establish the normative frequencies of DNA repair genes in South Indian healthy population and compare with HapMap populations. Genotyping was done on 128 healthy volunteers from South India, and the allele and genotype distributions were established. The minor allele frequency of Xeroderma pigmentosum group A ( XPA) G23A, Excision repair cross-complementing 2 ( ERCC2)/Xeroderma pigmentosum group D ( XPD) Lys751Gln, Xeroderma pigmentosum group G ( XPG) His46His, XPG Asp1104His, and X-ray repair cross-complementing group 1 ( XRCC1) Arg399Gln polymorphisms were 49.2%, 36.3%, 48.0%, 23.0%, and 34.0% respectively. Ethnic variations were observed in the frequency distribution of these polymorphisms between the South Indians and other HapMap populations. The present work forms the groundwork for cancer association studies and biomarker identification for treatment response and prognosis.

Population Analysis of Pharmacogenetic Polymorphisms Related to Acute Lymphoblastic Leukemia Drug Treatment

This study aimed to evaluate in the Brazilian population, the genotypes and population frequencies of pharmacogenetic polymorphisms involved in the response to drugs used in treatment of acute lymphoblastic leukemia (ALL), and to compare the data with data from the HapMap populations. There was significant differentiation between most population pairs, but few associations between genetic ancestry and SNPs in the Brazilian population were observed. AMOVA analysis comparing the Brazilian population to all other populations retrieved from HapMap pointed to a genetic proximity with the European population. These associations point to preclusion of the use of genetic ancestry as a proxy for predicting drug response. In this way, any study aiming to correlate genotype with drug response in the Brazilian population should be based on pharmacogenetic SNP genotypes.