Frequency of NAT2 and GSTP1 polymorphisms in the Kazakh population

Introduction: Phase II xenobiotic biotransformation enzymes perform detoxification of hydrophilic and often toxic Phase I products by glutathionetransferase (GST), UDP-glucuronosyltransferase (UDF), N-acetyltransferase (NAT) families and other enzymes. GST protein family metabolizes a large number of electrophilic xenobiotics, including drugs, by conjugating them with glutathione. Arylamine-N-acetyltransferase (NAT) catalyzes the acetylation of the aromatic and heterocyclic amines.Materials and methods: The current study has assessed the frequencies of NAT2 and GSTP1 genes polymorphisms in 326 healthy individuals from different regions of Kazakhstan by using Real-Time PCR and direct sequencing methods.Results: Allele frequencies were derived for NAT2*5 (0.54) and GSTP1 (0.27). GSTP1 alleles were in Hardy – Weinberg equilibrium (p > 0.05), while NAT2*5 (p = 0.00) were not.  The population differences between North, Northeast and South Kazakhstan regions were determined. Statistically significant differences in the frequency of genotypes were not found.Conclusion: Allelic polymorphisms of NAT2*5 and GSTP1 genes vary widely in different populations. Kazakh population was significantly different from Asian, Caucasoid, African-American and Hispanic ones by NAT2*5 and GSTP1 genes. Allelic variants of the NAT2*5 were detected with a low frequency in Asian populations. Allelic frequency in other world populations varies from 30 to 50%. The differences between Kazakh (0.54) and the world population were statistically significant (p < 0.05). The frequency of GSTP1 (rs1695) in the African American population is 42%. The frequency of GSTP1 in Asian populations varies from 11% to 23%, in Caucasoid populations it is about 30%. The differences between Kazakh population (0.27) and other populations selected from the literature were statistically significant (p < 0.05).The study of mutations in GSTP1 and NAT2 genes is necessary to assess the risk of the development of various diseases, such as cancer. Information on allelic polymorphisms also might be useful for personalized drug prescription for such drugs as cyclophosphamide, cisplatin, methotrexate, isoniazid, pyrazinamide, and rifampin

Pharmacogenetic research in Kazakhstan

Introduction: Pharmacogenomics is an emerging field of medicine that combines genetics and pharmacology. Pharmacogenomic research is relatively new in Kazahkstan, but, in recent years, significant progress has been made in this field. The National Scientific Laboratory for Biotechnology has launched several government-funded research projects focused on finding genetic markers that determine susceptibility to various drugs. Another goal of pharmacogenetic research in the laboratory is to find the pharmacogenomic markers that target cardiovascular diseases, accounting for allelic frequencies in selected genes in the Kazakh population. In addition, pharmacogenomic testing kits allow patients to choose the drug dosage. For example, the drug Warfarin has been developed within the framework of the "Technology Commercialization Project,” funded jointly by the Ministry of Education and Science of the Republic of Kazakhstan and the World Bank.Material and methods: The pharmacogenomic studies were conducted using the real-time PCR and direct DNA sequencing. DNA was isolated from venous blood or buccal cells, collected from patients.Results: To date, we have identified the most promising areas of research in the field of pharmacogenomics in Kazakhstan. The allelic frequencies of a number of polymorphisms in the Kazakh population have been calculated (CYP2C9, CYP2C19, CYP3A4, VKORC1, CYP4F2, GGCX, CYP2D6, CYP1A2, NAT2, GSTP1, SLC47A1). A unique repository of DNA samples was established and is being replenished during the implementation of aforementioned projects. Development of the testing kit for individual selection of Warfarin dosage is nearing completion. A patent, named "Method of Selection Based Dose Warfarin Genotyping for the Kazakh Population" has been recently obtained. An application for another patent, titled "Express Method of Correction of Warfarin Dosing, Based on Real-time PCR" has received positive evaluation. The results of domestic pharmacogenomic studies will allow a more rational selection of drugs and their dosage regimens specific to the Kazakh population

Wearable Communications in 5G: Challenges and Enabling Technologies

As wearable devices become more ingrained in our daily lives, traditional communication networks primarily designed for human being-oriented applications are facing tremendous challenges. The upcoming 5G wireless system aims to support unprecedented high capacity, low latency, and massive connectivity. In this article, we evaluate key challenges in wearable communications. A cloud/edge communication architecture that integrates the cloud radio access network, software defined network, device to device communications, and cloud/edge technologies is presented. Computation offloading enabled by this multi-layer communications architecture can offload computation-excessive and latency-stringent applications to nearby devices through device to device communications or to nearby edge nodes through cellular or other wireless technologies. Critical issues faced by wearable communications such as short battery life, limited computing capability, and stringent latency can be greatly alleviated by this cloud/edge architecture. Together with the presented architecture, current transmission and networking technologies, including non-orthogonal multiple access, mobile edge computing, and energy harvesting, can greatly enhance the performance of wearable communication in terms of spectral efficiency, energy efficiency, latency, and connectivity.Comment: This work has been accepted by IEEE Vehicular Technology Magazin

Polymorphisms in genes involved in the absorption, distribution, metabolism, and excretion of drugs in the Kazakhs of Kazakhstan

A list of SNPs that were not found in heterozygous or homozygous variants. (DOC 83 kb

Pharmacogenetic research in Kazakhstan

Introduction: Pharmacogenomics is an emerging field of medicine that combines genetics and pharmacology. Pharmacogenomic research is relatively new in Kazahkstan, but, in recent years, significant progress has been made in this field. The National Scientific Laboratory for Biotechnology has launched several government-funded research projects focused on finding genetic markers that determine susceptibility to various drugs. Another goal of pharmacogenetic research in the laboratory is to find the pharmacogenomic markers that target cardiovascular diseases, accounting for allelic frequencies in selected genes in the Kazakh population. In addition, pharmacogenomic testing kits allow patients to choose the drug dosage. For example, the drug Warfarin has been developed within the framework of the "Technology Commercialization Project,” funded jointly by the Ministry of Education and Science of the Republic of Kazakhstan and the World Bank. Material and methods: The pharmacogenomic studies were conducted using the real-time PCR and direct DNA sequencing. DNA was isolated from venous blood or buccal cells, collected from patients. Results: To date, we have identified the most promising areas of research in the field of pharmacogenomics in Kazakhstan. The allelic frequencies of a number of polymorphisms in the Kazakh population have been calculated (CYP2C9, CYP2C19, CYP3A4, VKORC1, CYP4F2, GGCX, CYP2D6, CYP1A2, NAT2, GSTP1, SLC47A1). A unique repository of DNA samples was established and is being replenished during the implementation of aforementioned projects. Development of the testing kit for individual selection of Warfarin dosage is nearing completion. A patent, named "Method of Selection Based Dose Warfarin Genotyping for the Kazakh Population" has been recently obtained. An application for another patent, titled "Express Method of Correction of Warfarin Dosing, Based on Real-time PCR" has received positive evaluation. The results of domestic pharmacogenomic studies will allow a more rational selection of drugs and their dosage regimens specific to the Kazakh population

Frequency of NAT2 and GSTP1 polymorphisms in the Kazakh population

Introduction: Phase II xenobiotic biotransformation enzymes perform detoxification of hydrophilic and often toxic Phase I products by glutathionetransferase (GST), UDP-glucuronosyltransferase (UDF), N-acetyltransferase (NAT) families and other enzymes. GST protein family metabolizes a large number of electrophilic xenobiotics, including drugs, by conjugating them with glutathione. Arylamine-N-acetyltransferase (NAT) catalyzes the acetylation of the aromatic and heterocyclic amines. Materials and methods: The current study has assessed the frequencies of NAT2 and GSTP1 genes polymorphisms in 326 healthy individuals from different regions of Kazakhstan by using Real-Time PCR and direct sequencing methods. Results: Allele frequencies were derived for NAT2*5 (0.54) and GSTP1 (0.27). GSTP1 alleles were in Hardy – Weinberg equilibrium (p > 0.05), while NAT2*5 (p = 0.00) were not.  The population differences between North, Northeast and South Kazakhstan regions were determined. Statistically significant differences in the frequency of genotypes were not found. Conclusion: Allelic polymorphisms of NAT2*5 and GSTP1 genes vary widely in different populations. Kazakh population was significantly different from Asian, Caucasoid, African-American and Hispanic ones by NAT2*5 and GSTP1 genes. Allelic variants of the NAT2*5 were detected with a low frequency in Asian populations. Allelic frequency in other world populations varies from 30 to 50%. The differences between Kazakh (0.54) and the world population were statistically significant (p < 0.05). The frequency of GSTP1 (rs1695) in the African American population is 42%. The frequency of GSTP1 in Asian populations varies from 11% to 23%, in Caucasoid populations it is about 30%. The differences between Kazakh population (0.27) and other populations selected from the literature were statistically significant (p < 0.05). The study of mutations in GSTP1 and NAT2 genes is necessary to assess the risk of the development of various diseases, such as cancer. Information on allelic polymorphisms also might be useful for personalized drug prescription for such drugs as cyclophosphamide, cisplatin, methotrexate, isoniazid, pyrazinamide, and rifampin

Polymorphisms of HLA-DRB1, -DQA1 and -DQB1 in inhabitants of Astana, the capital city of Kazakhstan.

BackgroundKazakhstan has been inhabited by different populations, such as the Kazakh, Kyrgyz, Uzbek and others. Here we investigate allelic and haplotypic polymorphisms of human leukocyte antigen (HLA) genes at DRB1, DQA1 and DQB1 loci in the Kazakh ethnic group, and their genetic relationship between world populations.Methodology/principal findingsA total of 157 unrelated Kazakh ethnic individuals from Astana were genotyped using sequence based typing (SBT-Method) for HLA-DRB1, -DQA1 and -DQB1 loci. Allele frequencies, neighbor-joining method, and multidimensional scaling analysis have been obtained for comparison with other world populations. Statistical analyses were performed using Arlequin v3.11. Applying the software PAST v. 2.17 the resulting genetic distance matrix was used for a multidimensional scaling analysis (MDS). Respectively 37, 17 and 19 alleles were observed at HLA-DRB1, -DQA1 and -DQB1 loci. The most frequent alleles were HLA-DRB1*07:01 (13.1%), HLA-DQA1*03:01 (13.1%) and HLA-DQB1*03:01 (17.6%). In the observed group of Kazakhs DRB1*07:01-DQA1*02:01-DQB1*02:01 (8.0%) was the most common three loci haplotype. DRB1*10:01-DQB1*05:01 showed the strongest linkage disequilibrium. The Kazakh population shows genetic kinship with the Kazakhs from China, Uyghurs, Mongolians, Todzhinians, Tuvinians and as well as with other Siberians and Asians.Conclusions/significanceThe HLA-DRB1, -DQA1 and -DQB1 loci are highly polymorphic in the Kazakh population, and this population has the closest relationship with other Asian and Siberian populations

Genetic risk factors for restenosis after percutaneous coronary intervention in Kazakh population

Background: After coronary stenting, the risk of developing restenosis is from 20 to 35 %. The aim of the present study is to investigate the association of genetic variation in candidate genes in patients diagnosed with restenosis in the Kazakh population. Methods: Four hundred fifty-nine patients were recruited to the study; 91 patients were also diagnosed with diabetes and were excluded from the sampling. DNA was extracted with the salting-out method. The patients were genotyped for 53 single-nucleotide polymorphisms. Genotyping was performed on the QuantStudio 12K Flex (Life Technologies). Differences in distribution of BMI score among different genotype groups were compared by analysis of variance (ANOVA). Also, statistical analysis was performed using R and PLINK v.1.07. Haplotype frequencies and LD measures were estimated by using the software Haploview 4.2. Results: A logistic regression analysis found a significant difference in restenosis rates for different genotypes. FGB (rs1800790) is significantly associated with restenosis after stenting (OR = 2.924, P = 2.3E−06, additive model) in the Kazakh population. CD14 (rs2569190) showed a significant association in the additive (OR = 0.08033, P = 2.11E−09) and dominant models (OR = 0.05359, P = 4.15E−11). NOS3 (rs1799983) was also highly associated with development of restenosis after stenting in additive (OR = 20.05, P = 2.74 E−12) and recessive models (OR = 22.24, P = 6.811E−10). Conclusions: Our results indicate that FGB (rs1800790), CD14 (rs2569190), and NOS3 (rs1799983) SNPs could be genetic markers for development of restenosis in Kazakh population. Adjustment for potential confounder factor BMI gave almost the same results

Neighbor-joining dendrogram based on HLA allele frequencies.

<p>Dendroram constructed by the neighbor-joining method showing the relationship between Kazakh populations with other populations based on the frequencies of HLA-DRB1 loc.</p

The Most frequent of DRB1-DQA1-DQB1 extended haplotypes and their frequencies in the Kazakh population (Astana).

a<p>Found in Buryats (22.0%); Khanty-Mansi (16.9%) Kazakhs (China) (8.3%).</p>b<p>Found in Italians (Sardinia) (25.3%); Russia (North-west) (9.0%); Kazakhs (China) (13.1%).</p>c<p>Found in Khanty-Mansi (8.1%); Italians (7.6%), Todzhinians (6.8%); Russia (North-west) (5.5%). Kazakhs (China) (4.8%);</p>d<p>Found in South Korea (2.9%).</p>e<p>Not found in any other population.</p>f<p>Found in Todzhinians (22.5%); English (14.1%), Australia Aborigine (10.0%); Russia (North-west) (9.0%); Kazakhs (China) (2.4%).</p>g<p>Found in Italians (14.1%); Slovenes (11.4%).</p>h<p>Found in Australia Aborigine (7.0%).</p>i<p>Found in Japan (8.2%); Mongolians (6.5%); Kazakhs (China) (2.4%).</p>j<p>Found in Khanty-Mansi (8.1%); Italians (7.6%); Kazakhs (China) (4.8%).</p>k<p>Found in Cameroon Yaounde (1.2%).</p>l<p>Found in Italians (1.9%); Tuva (1.1%).</p><p>The Most frequent of DRB1-DQA1-DQB1 extended haplotypes and their frequencies in the Kazakh population (Astana).</p