Polygenic scores for cardiovascular risk factors improve estimation of clinical outcomes in CCB treatment compared to pharmacogenetic variants alone.

Pharmacogenetic variants are associated with clinical outcomes during Calcium Channel Blocker (CCB) treatment, yet whether the effects are modified by genetically predicted clinical risk factors is unknown. We analyzed 32,000 UK Biobank participants treated with dihydropiridine CCBs (mean 5.9 years), including 23 pharmacogenetic variants, and calculated polygenic scores for systolic and diastolic blood pressures, body fat mass, and other patient characteristics. Outcomes included treatment discontinuation and heart failure. Pharmacogenetic variant rs10898815-A (NUMA1) increased discontinuation rates, highest in those with high polygenic scores for fat mass. The RYR3 variant rs877087 T-allele alone modestly increased heart failure risks versus non-carriers (HR:1.13, p = 0.02); in patients with high polygenic scores for fat mass, lean mass, and lipoprotein A, risks were substantially elevated (HR:1.55, p = 4 × 10-5). Incorporating polygenic scores for adiposity and lipoprotein A may improve risk estimates of key clinical outcomes in CCB treatment such as treatment discontinuation and heart failure, compared to pharmacogenetic variants alone.

Influence of pharmacogenomic polymorphisms on allopurinol-induced cutaneous adverse drug reactions in Thai patients.

BACKGROUND: Allopurinol has been causing substantial morbidity and mortality particularly in Asian population by producing cutaneous adverse drug reactions (cADRs). Nonetheless, there are no data describing whether other genetics are a valid marker for prediction of allopurinol-induced cADRs patients in addition to HLA-B*58:01 allele. The goal of this study was to identify suitable single nucleotide polymorphisms (SNPs) for allopurinol induced cADRs among Thai patients. METHODS: We conducted a case-control association study after enrolling 57 Thai patients with allopurinol induced cADRs and 101 allopurinol-tolerant controls. The genetic biomarkers and associated SNPs located on chromosome 6p21 were examined by TaqMan® SNP genotyping assays in both the cases and the controls. RESULTS: Out of fifteen SNPs in nine genes, we found four combined SNPs (rs3099844 of HCP5, rs9263726 of PSORS1C1, rs9263733 of POLR2LP, and rs9263745 of CCHCR1) were significantly associated with allopurinol-induced cADRs compared to the tolerant controls (OR 73.2; 95% CI 24.2-266.8; P = 1.9 × 10- 24). The overall sensitivity, specificity, positive predictive value and negative predictive value of these combinations were 84%, 94%, 9%, and 100%, respectively. However, the variant alleles of these SNP combinations were detected in 89.5% (51/57) of the cases. Moreover, the HLA-B*58:01 allele was observed in 86.0% of patients with allopurinol-induced cADRs, but only in 4.0% of tolerant controls (OR: 137.2; 95% CI: 38.3-670.5 and p-value = 1.7 × 10- 27). CONCLUSIONS: Thus, this research confirms the association between the specific HLA-B*58:01 allele and all phenotypes of allopurinol-induced cADRs in Thais. Furthermore, there was found the combined four SNPs (rs3099844, rs9263726, rs9263733, and rs9263745) could be used as alternative novel biomarkers for predicting cADRs in patients taking allopurinol.

Very important pharmacogenetic variants landscape and potential clinical relevance in the Zhuang population from Yunnan province.

The gradual evolution of pharmacogenomics has shed light on the genetic basis for inter-individual drug response variations across diverse populations. This study aimed to identify pharmacogenomic variants that differ in Zhuang population compared with other populations and investigate their potential clinical relevance in gene-drug and genotypic-phenotypic associations. A total of 48 variants from 24 genes were genotyped in 200 Zhuang subjects using the Agena MassARRAY platform. The allele frequencies and genotype distribution data of 26 populations were obtained from the 1000 Genomes Project, followed by a comparison and statistical analysis. After Bonferroni correction, significant differences in genotype frequencies were observed of CYP3A5 (rs776746), ACE (rs4291), KCNH2 (rs1805123), and CYP2D6 (rs1065852) between the Zhuang population and the other 26 populations. It was also found that the Chinese Dai in Xishuangbanna, China, Han Chinese in Beijing, China, and Southern Han Chinese, China showed least deviation from the Zhuang population. The Esan in Nigeria, Gambian in Western Division, The Gambia, and Yoruba in Ibadan, Nigeria exhibited the largest differences. This was also proved by structural analysis, Fst analysis and phylogenetic tree. Furthermore, these differential variants may be associated with the pharmacological efficacy and toxicity of Captopril, Amlodipine, Lisinopril, metoclopramide, and alpha-hydroxymetoprolol in the Zhuang population. Our study has filled the gap of pharmacogenomic information in the Zhuang population and has provided a theoretical framework for the secure administration of drugs in the Zhuang population.

Landscape of pharmacogenetic variants associated with non-insulin antidiabetic drugs in the Indian population.

INTRODUCTION: Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants. RESEARCH DESIGN AND METHODS: We mined 1029 Indian whole genomes for PGx variants, drug-drug interaction (DDI) and drug-drug-gene interactions (DDGI) associated with 44 NIADs. Population-wise allele frequencies were estimated and compared using Fisher's exact test. RESULTS: Overall, we found 76 known and 52 predicted deleterious common PGx variants associated with response to type 2 diabetes therapy among Indians. We report remarkable interethnic differences in the relative cumulative counts of decreased and increased response-associated alleles across NIAD classes. Indians and South Asians showed a significant excess of decreased metformin response-associated alleles compared with other global populations. Network analysis of shared PGx genes predicts high DDI risk during coadministration of NIADs with other metabolic disease drugs. We also predict an increased CYP2C19-mediated DDGI risk for CYP3A4/3A5-metabolized NIADs, saxagliptin, linagliptin and glyburide when coadministered with proton-pump inhibitors (PPIs). CONCLUSIONS: Indians and South Asians have a distinct PGx profile for antidiabetes drugs, marked by an excess of poor treatment response-associated alleles for various NIAD classes. This suggests the possibility of a population-specific reduced drug response in atleast some NIADs. In addition, our findings provide an actionable resource for accelerating future diabetes PGx studies in Indians and South Asians and reconsidering NIAD dosing guidelines to ensure maximum efficacy and safety in the population.

The landscape of very important pharmacogenes variants and potential clinical relevance in the Chinese Jingpo population: a comparative study with worldwide populations.

BACKGROUND: Pharmacogenomics is a facet of personalized medicine that explores how genetic variants affect drug metabolism and adverse drug reactions. Therefore, this study aims to detect distinct pharmacogenomic variations among the Jingpo population and explore their clinical correlation with drug metabolism and toxicity. METHODS: Agena MassARRAY Assay was used to genotype 57 VIP variants in 28 genes from 159 unrelated Jingpo participants. Subsequently, the chi-squared test and Bonferroni's statistical tests were utilized to conduct a comparative analysis of genotypes and allele frequencies between the Jingpo population and the other 26 populations from the 1000 Genome Project. RESULTS: We discovered that the KHV (Kinh in Ho ChiMinh City, Vietnam), CHS (Southern Han Chi-nese, China) and JPT (Japanese in Tokyo, Japan) exhibited the smallest differences from the Jingpo with only 4 variants, while ESN (Esan in Nigeria) exhibited the largest differences with 30 variants. Besides, a total of six considerably different loci (rs4291 in ACE, rs20417 in PTGS2, rs1801280 and rs1799929 in NAT2, rs2115819 in ALOX5, rs1065852 in CYP2D6, p < 3.37 × 10-5) were identified in this study. According to PharmGKB, rs20417 (PTGS2), rs4291 (ACE), rs2115819 (ALOX5) and rs1065852 (CYP2D6) were found to be associated with the metabolism efficiency of non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, montelukast and tamoxifen, respectively. Meanwhile, rs1801280 and rs1799929 (NAT2) were found to be related to drug poisoning with slow acetylation. CONCLUSION: Our study unveils distinct pharmacogenomic variants in the Jingpo population and discovers their association with the metabolic efficiency of NSAIDs, montelukast, and tamoxifen.

Should secondary pharmacogenomic variants be actively screened and reported when diagnostic genome-wide sequencing is performed in a child?

This white paper was prepared by the Global Alliance for Genomics and Health Regulatory and Ethics Work Stream's Pediatric Task Team to review and provide perspective with respect to ethical, legal, and social issues regarding the return of secondary pharmacogenomic variants in children who have a serious disease or developmental disorder and are undergoing exome or genome sequencing to identify a genetic cause of their condition. We discuss actively searching for and reporting pharmacogenetic/genomic variants in pediatric patients, different methods of returning secondary pharmacogenomic findings to the patient/parents and/or treating clinicians, maintaining these data in the patient's health record over time, decision supports to assist using pharmacogenetic results in future treatment decisions, and sharing information in public databases to improve the clinical interpretation of pharmacogenetic variants identified in other children. We conclude by presenting a series of points to consider for clinicians and policymakers regarding whether, and under what circumstances, routine screening and return of pharmacogenomic variants unrelated to the indications for testing is appropriate in children who are undergoing genome-wide sequencing to assist in the diagnosis of a suspected genetic disease.

Genome-Wide Association Study Identifies Pharmacogenomic Variants Associated With Metformin Glycemic Response in African American Patients With Type 2 Diabetes.

OBJECTIVE: Metformin is the most common treatment for type 2 diabetes (T2D). However, there have been no pharmacogenomic studies for T2D in which a population of color was used in the discovery analysis. This study sought to identify genomic variants associated with metformin response in African American patients with diabetes. RESEARCH DESIGN AND METHODS: Patients in the discovery set were adult, African American participants from the Diabetes Multi-omic Investigation of Drug Response (DIAMOND), a cohort study of patients with T2D from a health system serving southeast Michigan. DIAMOND participants had genome-wide genotype data and longitudinal electronic records of laboratory results and medication fills. The genome-wide discovery analysis identified polymorphisms correlated to changes in glycated hemoglobin (HbA1c) levels among individuals on metformin monotherapy. Lead associations were assessed for replication in an independent cohort of African American participants from Kaiser Permanente Northern California (KPNC) and in European American participants from DIAMOND. RESULTS: The discovery set consisted of 447 African American participants, whereas the replication sets included 353 African American KPNC participants and 466 European American DIAMOND participants. The primary analysis identified a variant, rs143276236, in the gene ARFGEF3, which met the threshold for genome-wide significance, replicated in KPNC African Americans, and was still significant in the meta-analysis (P = 1.17 × 10-9). None of the significant discovery variants replicated in European Americans DIAMOND participants. CONCLUSIONS: We identified a novel and biologically plausible genetic variant associated with a change in HbA1c levels among African American patients on metformin monotherapy. These results highlight the importance of diversity in pharmacogenomic studies.

Mining local exome and HLA data to characterize pharmacogenetic variants in Saudi Arabia.

Pharmacogenomics (PGx) is a promising field of precision medicine where efficacy of drugs is maximized while side effects are minimized for individual patients. Knowledge of the frequency of PGx-relevant variants (pharmacovariants) in the local population is a pre-requisite to informed policy making. Unfortunately, such knowledge is largely lacking from the Middle East. Here, we describe the use of a large clinical exome database (n = 13,473) and HLA haplotypes (n = 64,737) from Saudi Arabia, one of the largest countries in the Middle East, along with previously published data from the local population to ascertain allele frequencies of known pharmacovariants. In addition, we queried another exome database (n = 816) of well-phenotyped research subjects from Saudi Arabia to discover novel candidate variants in known PGx genes (pharmacogenes). Although our results show that only 26% (63/242) of class 1A/1B PharmGKB variants were identified, we estimate that 99.57% of the local population have at least one such variant. This translates to a minimum estimated impact of 9% of medications dispensed by our medical center annually. We also highlight the contribution of rare variants where 71% of the pharmacogenes devoid of common pharmacovariants had at least one potentially deleterious rare variant. Thus, we show that approaches that go beyond the use of commercial PGx kits that have been optimized for other populations should be implemented to ensure universal and equitable access of all members of the local population to personalized prescription practices.

Population Pharmacogenomics for Health Equity.

Health equity means the opportunity for all people and populations to attain optimal health, and it requires intentional efforts to promote fairness in patient treatments and outcomes. Pharmacogenomic variants are genetic differences associated with how patients respond to medications, and their presence can inform treatment decisions. In this perspective, we contend that the study of pharmacogenomic variation within and between human populations-population pharmacogenomics-can and should be leveraged in support of health equity. The key observation in support of this contention is that racial and ethnic groups exhibit pronounced differences in the frequencies of numerous pharmacogenomic variants, with direct implications for clinical practice. The use of race and ethnicity to stratify pharmacogenomic risk provides a means to avoid potential harm caused by biases introduced when treatment regimens do not consider genetic differences between population groups, particularly when majority group genetic profiles are assumed to hold for minority groups. We focus on the mitigation of adverse drug reactions as an area where population pharmacogenomics can have a direct and immediate impact on public health.

Pharmacogenomic variants affecting efficacy and toxicity of statins in a south Asian population from Sri Lanka.

Aim: To describe the diversity of pharmacogenetic variants of statins among Sri Lankans. Materials & methods: Variant data of relevant genes were obtained from an anonymized database of 426 Sri Lankans. Minor allele frequencies (MAFs) were compared with published data from other populations. Results: The MAF of SLCO1B1*5 (rs4149056 [T>C]) was 18.19% (95% CI: 14.53-21.85). MAFs of CYP2C9*2 (rs1799853 [C>T]) and CYP2C9*3 (rs1057910 [A>C]) were 2.58% (95% CI: 1.08-4.08) and 10.30% (95% CI: 7.75-13.61), respectively. MAFs of rs2231142 (G>T) (ABCG2), rs7412 (C>T) (APOE) and rs20455 (A>G) (KIF6) variants were 10.68% (95% CI: 7.76-13.60), 3.52% (95% CI: 1.77-5.27) and 50.7% (95% CI: 45.96-55.45), respectively. Compared with western/other Asian populations, rs20455 (A>G), CYP2C9*3 (A>C) and SLCO1B1*5 (T>C) variants were significantly higher in Sri Lankans. Conclusion: Variants that affect efficacy of statins (KIF6 [rs20455], CYP2C9*3) and increase risk of statin-induced myotoxicity (SLCO1B1*5 and CYP2C9*3) were prevalent in higher frequencies among Sri Lankans compared with western populations.

Towards more accurate pharmacogenomic variant effect predictions.

Tweetable abstract Accurate variant interpretation has become a key bottleneck for the translation of an individual's pharmacogenome into actionable recommendations. We recommend an integrated use of multiplexed assays, structure-based predictions and biobank data to develop more accurate effect predictors.

Multidrug resistant 1 (MDR1) C3435T and G2677T gene polymorphism: impact on the risk of acute rejection in pediatric kidney transplant recipients.

BACKGROUND: Tacrolimus is the backbone drug in kidney transplantation. Single nucleotide polymorphism of Multidrug resistant 1 gene can affect tacrolimus metabolism consequently it can affect tacrolimus trough level and incidence of acute rejection. The aim of this study is to investigate the impact of Multidrug resistant 1 gene, C3435T and G2677T Single nucleotide polymorphisms on tacrolimus pharmacokinetics and on the risk of acute rejection in pediatric kidney transplant recipients. METHODS: Typing of Multidrug resistant 1 gene, C3435T and G2677T gene polymorphism was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for 83 pediatric kidney transplant recipients and 80 matched healthy controls. RESULTS: In Multidrug resistant 1 gene (C3435T), CC, CT genotypes and C allele were significantly associated with risk of acute rejection when compared to none acute rejection group (P = 0.008, 0.001 and 0.01 respectively). The required tacrolimus doses to achieve trough level were significantly higher among CC than CT than TT genotypes through the 1st 6 months after kidney transplantation. While, in Multidrug resistant 1 gene (G2677T), GT, TT genotypes and T allele were associated with acute rejection when compared to none acute rejection (P = 0.023, 0.033 and 0.028 respectively). The required tacrolimus doses to achieve trough level were significantly higher among TT than GT than GG genotypes through the 1st 6 months after kidney transplantation. CONCLUSION: The C allele, CC and CT genotypes of Multidrug resistant 1 gene (C3435T) and the T allele, GT and TT genotypes of Multidrug resistant 1 gene (G2677T) gene polymorphism may be risk factors for acute rejection and this can be attributed to their effect on tacrolimus pharmacokinetics. Tacrolimus therapy may be tailored according to the recipient genotype for better outcome.

Can Pharmacogenetic Variants in TPMT, MTHFR and SLCO1B1 Genes Be Used as Potential Markers of Outcome Prediction in Systemic Sclerosis Patients?

Systemic sclerosis (SSc) is a rare connective tissue disorder with highest morbidity and mortality among rheumatologic diseases. Disease progression is highly heterogeneous between patients, implying a strong need for individualization of therapy. Four pharmacogenetic variants, namely TPMT rs1800460, TPMT rs1142345, MTHFR rs1801133 and SLCO1B1 rs4149056 were tested for association with severe disease outcomes in 102 patients with SSc from Serbia treated either with immunosuppressants azathioprine (AZA) and methotrexate (MTX) or with other types of medications. Genotyping was performed using PCR-RFLP and direct Sanger sequencing. R software was used for statistical analysis and development of polygenic risk score (PRS) model. Association was found between MTHFR rs1801133 and higher risk for elevated systolic pressure in all patients except those prescribed with MTX, and higher risk for kidney insufficiency in patients prescribed with other types of drugs. In patients treated with MTX, variant SLCO1B1 rs4149056 was protective against kidney insufficiency. For patients receiving MTX a trend was shown for having a higher PRS rank and elevated systolic pressure. Our results open a door wide for more extensive research on pharmacogenomics markers in patients with SSc. Altogether, pharmacogenomics markers could predict the outcome of patients with SSc and help in prevention of adverse drug reactions.

Profiling of pharmacogenomic variants in CYP2D6 and DPYD in indigenous Arab breast cancer patients.

Aim: The indigenous Arab population is underrepresented in genomic studies and the landscape of actionable pharmacogenomic variants among Arab breast cancer patients remains unclear. Materials & methods: Exome sequencing was performed on 220 unselected Arab female breast cancer patients and germline variants in CYP2D6 and DPYD were profiled using a deep learning method. Results: In total, 13 (5.9%) patients had clinically actionable results and 56 (25.5%) carried an allele in DYPD or CYP2D6 with unknown impact on drug metabolism. In addition, four unique novel missense variants were discovered, including one in CYP2D6 (p.Arg64Leu) with high predicted pathogenicity. Conclusion: A nontrivial subset of Arab breast cancer patients can potentially benefit from pretreatment molecular profiling, and further study is needed to improve characterization of the pharmacogenomic landscape.

The prevalence of pharmacogenetic variants of vitamin K epoxide reductase complex subunit 1 gene (rs9923231), cytochrome P450 family 2 subfamily C member 9 gene (rs1799853) and cytochrome P450 family 3 subfamily-A member-5 gene (rs776746) among 13 ethnic groups of Pakistan.

BACKGROUND: Pharmacogenomics (PGx) plays a central role in the selection of targeted therapies that underpins precision-medicine. We investigated the prevalence of three important pharmacogenetic variants of VKORC1, CYP2C9, and CYP3A5 genes among Pakistani populations. METHODS: A total of 1104 individuals were included representing thirteen major ethnicities. Samples were genotyped by using PCR-RFLP analysis. The allelic and genotypic frequencies of the three SNV's were calculated and were compared with the world's population data (ALFA, gnomAD, and 1000Genome, 1 K databases), using the chi-square test. RESULTS: We found overall frequencies of functional-alleles of VKORC1 0.43, CYP2C9 0.94, and CYP3A5 0.14 in our population. Data showed a low prevalence of homozygous functional genotypes of VKORC1 (0.18; 0.0-0.45) and CYP3A5 (0.04; 0.0-0.22), and a high frequency of CYP2C9 (0.885; 0.80-1.0) across ethnicities. Genotyping distribution of VKCOR1 functional genotype was varied across ethnic groups such as 0.0-0.10 in Brahuis and Mohanas, Sindhis, Rajputs, and Gujjars populations, 0.11-0.20 in Makranis, Parsis, and Burusho populations, and 0.20-0.30 in Kalash, Kashmiris and Baloch populations. The highest VKORC1 (CC) was found in Pathans (0.45) and Hazaras (0.39) populations. Interestingly, we found a high prevalence of functional genotype CYP2C9 (rs1799853; C) and non-functional genotype of CYP3A5 (rs776746; T) across various ethnic groups of Pakistan. CONCLUSION: Data regarding prevalence of clinically important pharmacogenomics SNVs could be useful in drug adjustment and avoiding adverse drug reactions in a specific ethnic population. This could help in moving current medical practices toward precision medicine in our part of the world.

DPYD genotyping and predicting fluoropyrimidine toxicity: where do we stand?

Fluoropyrimidines (FPs) are antineoplastic drugs widely used in the treatment of various solid tumors. Nearly 30% of patients treated with FP chemotherapy experience severe FP-related toxicity, and in some cases, toxicity can be fatal. Patients with reduced activity of DPD, the main enzyme responsible for the breakdown of FP, are at an increased risk of experiencing severe FP-related toxicity. While European regulatory agencies and clinical societies recommend pre-treatment DPD deficiency screening for patients starting treatment with FPs, this is not the case with American ones. Pharmacogenomic guidelines issued by several pharmacogenetic organizations worldwide recommend testing four DPD gene (DPYD) risk variants, but these can predict only a proportion of toxicity cases. New evidence on additional common DPYD polymorphisms, as well as identification and functional characterization of rare DPYD variants, could partially address the missing heritability of DPD deficiency and FP-related toxicity.

Calcium-channel blockers: Clinical outcome associations with reported pharmacogenetics variants in 32 000 patients.

AIMS: Pharmacogenetic variants impact dihydropyridine calcium-channel blockers (dCCBs; e.g., amlodipine) treatment efficacy, yet evidence on clinical outcomes in routine primary care is limited. Reported associations in pharmacogenomics knowledge base PharmGKB have weak supporting evidence. We aimed to estimate associations between reported pharmacogenetic variants and incident adverse events in a community-based cohort prescribed dCCB. METHODS: We analysed up to 32 360 UK Biobank participants prescribed dCCB in primary care (from UK general practices, 1990-2017). We investigated 23 genetic variants. Outcomes were incident diagnosis of coronary heart disease, heart failure (HF), chronic kidney disease, oedema and switching antihypertensive medication. RESULTS: Participants were aged 40-79 years at first dCCB prescription. Carriers of rs877087 T allele in RYR3 had increased risk of hazard ratio (HF 1.13: 95% confidence interval 1.02 to 1.25, P = .02). Although nonsignificant after multiple testing correction, the association is consistent with prior evidence. We estimated that if rs877087 T allele could experience the same treatment effect as noncarriers, the incidence of HF in patients prescribed dCCB would reduce by 9.2% (95% confidence interval 3.1 to 15.4). In patients with a history of heart disease prior to dCCB (n = 2296), rs877087 homozygotes had increased risk of new coronary heart disease or HF compared to CC variant. rs10898815 in NUMA1 and rs776746 in CYP3A5 increased likelihood of switching to an alternative antihypertensive. The remaining variants were not strongly or consistently associated with studied outcomes. CONCLUSION: Patients with common genetic variants in NUMA1, CYP3A5 and RYR3 had increased adverse clinical outcomes. Work is needed to establish whether outcomes of dCCB prescribing could be improved by prior knowledge of pharmacogenetics variants supported by clinical evidence of association with adverse events.

Very important pharmacogenes polymorphism landscape and potential clinical relevance in the Chinese Mongolian.

PURPOSE: Our study genotyped pharmacogenes in 200 individuals from Inner Mongolia Autonomous Region, China. Aim to find distinct pharmacogenomic variations among the Mongolian population and to investigate the potential clinically operable gene-drug connection and genotype-phenotype correlation of differential variation in the Mongolian population. METHODS: We sampled 61 variations of 28 genes in PharmGKB and genotyped them using Agena MassARRAY Assay. We also obtained the allele frequency and genotype distribution data of 26 populations from the 1000 Genomes Project (1000G), and then conducted comparison and statistical analysis. RESULTS: After Bonferroni correction, there were significant genotype frequency distribution differences between the Mongolian and 26 populations: PTGS2 (rs20417), NAT2 (rs1801280, rs1799929, and rs1208), ALOX5(rs2115819), and CYP2D6 (rs1065852). It was also found that the KHV showed the smallest differences from the Mongolian and the GWD showed the largest differences. Furthermore, the differences in variants might be related to the risk of non-steroidal anti-inflammatory drug use, the slow acetylation phenotype, and other pharmacological effectiveness and toxicity in the Mongolian population. CONCLUSION: Our study demonstrates different pharmacogenomic variants in the Mongolian and fills the gaps in pharmacogenomic information of the Mongolian. Our analysis of VIPs variants in the Mongolian population may contribute to the development of safer treatment regimens and the use of personalized treatment approaches.