Analysis of Comprehensive Pharmacogenomic Profiling of VIP Variants Among the Genetically Isolated Chechen Subpopulation from Jordan.

BACKGROUND: Profiling rare variants in isolated populations can significantly clarify and understand the development of a clinically relevant process. Therefore, leading to a better identifying novel targeted treatment. OBJECTIVE: This study aimed to determine the allele frequencies of 56 single nucleotide polymorphisms (SNPs) within several important pharmacogenes. METHODS: This study consisted of 166 unrelated subjects from a genetically isolated group (Chechen) who were living in Jordan. In this study, the distribution of the variants among Chechen was compared to other ethnic groups available at two databases (Genome 1000 and (ExAC)). The frequency of genotypes and alleles was calculated and tested using the chi-square test and the Hardy-Weinberg equilibrium equation (HWE). RESULTS: Our results revealed that the distribution of allele frequencies within different pharmacogenes among Chechen showed different similarities with other populations. The CEU and TSI showed the highest resemblance with the Chechen population (75% similarity), in contrast to LWK which had the lowest similarity (30%). CONCLUSION: This study sheds light on clinically relevant SNPs to enhance medical research and apply pharmacogenomics in clinical settings.

Genetic Polymorphisms of Pharmacogenes among the Genetically Isolated Circassian Subpopulation from Jordan.

Several genetic variants have been identified that cause variation among different populations and even within individuals of a similar descent. This leads to interindividual variations in the optimal dose of the drug that is required to sustain the treatment efficiency. In this study, 56 single nucleotide polymorphisms (SNPs) within several pharmacogenes were analyzed in 128 unrelated subjects from a genetically isolated group of Circassian people living in Jordan. We also compared these variant distributions to other ethnic groups that are available at two databases (Genome 1000 and eXAC). Our results revealed that the distribution of allele frequencies within genes among Circassians in Jordan showed similarities and disparities when compared to other populations. This study provides a powerful base for clinically relevant SNPs to enhance medical research and future pharmacogenomic studies. Rare variants detected in isolated populations can significantly guide to novel loci involved in the development of clinically relevant traits.

Investigation of the forensic GlobalFiler loci in the genetically isolated Circassian subpopulation in Jordan.

Circassians are a Caucasian ethnic group who make up a significant minority in Jordan. Although other ethnic groups have been the subject of forensic genetic analysis, no published study has investigated the forensic genetic efficiency of short tandem repeats (STRs) in Circassians, neither in Jordan nor in any other country. The main objective of the current study is to determine the allelic frequencies and evaluate the forensic efficiency parameters of 21 highly polymorphic autosomal STR loci among the Circassian subpopulation in Jordan. The GlobalFiler loci were amplified using DNA extracted from the whole blood samples of 150 Jordanian Circassians. The SE33 locus was found to be the most informative and polymorphic STR marker while TPOX was the least informative. However, allele 8 of TPOX was the most common across all of the investigated 21 loci in Jordanian Circassians. The combined matching probability (CMP) and combined power of discrimination (CPD) were 5.02E-24 and 0.9999999, respectively.

Assessing the forensic efficiency of the GlobalFiler STR loci among the genetically isolated Chechen subpopulation in Jordan.

Short tandem repeats (STRs) are a widely utilized tool in forensic applications, the latter of which range from human identification and paternity testing to population analysis. The GlobalFiler STR loci, which includes 21 autosomal STRS, were analyzed in the Chechen subpopulation of Jordan. Whole blood samples were withdrawn from 159 Jordanian Chechen individuals, and genomic DNA was extracted from each sample. The GlobalFiler™ kit PCR Amplification Kit amplified and analyzed the STR loci on the 3130xl Genetic Analyzer using GeneMapper ID-X software. The combined match probability for the 21 autosomal STR loci was calculated to be 1.06 × 10-24, a number that is highly discriminatory and informative. The SE33 (0.983) and TPOX (0.806) loci exhibited the highest and lowest powers of discrimination, respectively. Conclusively, the current study indicates that the GlobalFiler loci have a high utility in the Jordanian Chechen population, possibly paving the way for the future establishment of a reference population database in Jordan.

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.

Diabetes mellitus in two genetically distinct populations in Jordan. A Comparison between Arabs and Circassians/Chechens Living with Diabetes.

OBJECTIVES: To compare clinical, anthropometric, and laboratory characteristics in diabetes type 2 patients of 2 genetically-distinct ethnicities living in Jordan, Arabs and Circassians/Chechens.  Methods: This cross sectional ethnic comparison study was conducted in King Abdullah University Hospital, Irbid and The National Center for Diabetes, Endocrinology, and Genetics, Amman, Jordan between June 2013 and February 2014. A sample of 347 (237 Arab and 110 Circassian/Chechen) people living with diabetes were included in the study. Data were collected through direct interviews with the participants. Clinical data were collected using a questionnaire and anthropometric measurements. Laboratory data were extracted from the patients' medical records. Results: More Arabs with diabetes had hypertension as a comorbidity than Circassians/Chechens with diabetes. Arabs living with diabetes were generally more obese, whereas Circassians/Chechens living with diabetes had worse lipid control. Arabs with diabetes had higher means of glycated haemoglobin (HbA1c) and fasting blood sugar, and more Arabs with diabetes had unsatisfactory glycemic control (60.6%) than Circassians/Chechens with diabetes (38.2%) (HbA1c ≥7.0%). Most participants (88.8%) had at least one lipid abnormality (dyslipidemia).  Conclusion: Multiple discrepancies among the 2 ethnic diabetic populations were found. New diabetes management recommendations and policies should be used when treating people living with diabetes of those ethnicities, particularly in areas of glycemic control, lipid control, and obesity.