Pharmacogenomics and Personalized Medicine最新文献

{"title":"Association Between SNPs in the One-Carbon Metabolism Pathway and the Risk of Female Breast Cancer in a Chinese Population.","authors":"Xuhong Wang,&nbsp;Mengqiu Xiong,&nbsp;Bei Pan,&nbsp;William C S Cho,&nbsp;Jin Zhou,&nbsp;Shukui Wang,&nbsp;Bangshun He","doi":"10.2147/PGPM.S328612","DOIUrl":"https://doi.org/10.2147/PGPM.S328612","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study is to assess the relationship between the single-nucleotide polymorphism (SNP) in the one-carbon metabolism pathway (<i>MTR</i> rs1805087; <i>MTHFR</i> rs1801133; <i>ALDH1L1</i> rs2002287, rs2276731; <i>DNMT1</i> rs16999593, rs2228611; <i>DNMT3B</i> rs2424908) and the risk of female breast cancer (BC) in a Chinese population.</p><p><strong>Methods: </strong>A population-based case-control study was conducted, involving a total of 439 BC patients and 439 age-matched healthy controls. We adopted Sequence MASSarray to identify genotyping, and used immunohistochemistry (IHC) to test the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) in tumor tissue.</p><p><strong>Results: </strong>We found that rs16999593 (TC/CC vs TT: adjusted OR=1.38, 95% CI: 1.03-1.84, <i>p</i>=0.030) was associated with an increased risk of BC, while rs2228611 was related to a decreased BC risk (GA/AA vs GG: adjusted OR=0.74, 95% CI: 0.56-0.97, <i>p</i>=0.030). In addition, stratified analysis revealed that <i>DNMT1</i> rs16999593, rs2228611 and <i>ALDH1L1</i> rs2002287 contributed to the risk of BC, with associations with ER, PR and HER-2 expression.</p><p><strong>Conclusion: </strong>In summary, this study revealed that <i>DNMT1</i> rs16999593 and rs2228611 were associated with BC risk.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"9-16"},"PeriodicalIF":1.9,"publicationDate":"2022-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/26/8d/pgpm-15-9.PMC8761026.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39833978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Missense Mutation in <i>TWNK</i> Gene Causing Perrault Syndrome Type 5 in a Chinese Family and Review of the Literature.","authors":"Lan Wei,&nbsp;Ling Hou,&nbsp;Yan-Qin Ying,&nbsp;Xiao-Ping Luo","doi":"10.2147/PGPM.S341172","DOIUrl":"https://doi.org/10.2147/PGPM.S341172","url":null,"abstract":"<p><strong>Background: </strong>Perrault syndrome (PRLTS) is a rare autosomal recessive disorder characterized by sensorineural hearing loss in both sexes and ovarian dysfunction in females. In some cases, patients present with a diversity of neurological signs. Six genes are known to cause Perrault syndrome.</p><p><strong>Case report: </strong>We report an 11-year-old Chinese girl with delayed gonadal development, sensorineural hearing loss, and neurologic manifestations. Genetic etiology was identified by whole-exome sequencing and confirmed via Sanger sequencing. Compound heterozygous variants with one novel variant c.1752C>A (p.D584E) and one known pathogenic variant c.1172G>A (p.R391H) in <i>TWNK</i> were discovered in the child and inherited from her parents, respectively.</p><p><strong>Conclusion: </strong>The compound heterozygous variants c.1172G>A (p.R391H) and c.1752C>A (p.D584E) of the <i>TWNK</i> gene probably underlie PRLTS type 5 (PRLTS5). This study expands the mutation spectrum of <i>TWNK</i> pathogenicity in the PRLTS5 phenotype.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1-8"},"PeriodicalIF":1.9,"publicationDate":"2022-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/bf/pgpm-15-1.PMC8754503.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39824705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship Between <i>KCNQ1</i> Polymorphism and Type 2 Diabetes Risk in Northwestern China.","authors":"Jing Xu,&nbsp;Wei Zhang,&nbsp;Wei Song,&nbsp;Jiaqi Cui,&nbsp;Yanni Tian,&nbsp;Huan Chen,&nbsp;Pan Huang,&nbsp;Shujun Yang,&nbsp;Lu Wang,&nbsp;Xin He,&nbsp;Lin Wang,&nbsp;Bingyin Shi,&nbsp;Wei Cui","doi":"10.2147/PGPM.S340813","DOIUrl":"https://doi.org/10.2147/PGPM.S340813","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to explore the relationship between KCNQ1 polymorphism and type 2 diabetes mellitus (T2DM) risk in the population of Northwest China.</p><p><strong>Patients and methods: </strong>Case-control strategy was used to reveal the correlation between <i>KCNQ1</i> polymorphism and T2DM risk, and MDR analysis clarified the influence of <i>KCNQ1</i> polymorphism interaction on T2DM risk. The related proteins, functions, and signal pathways of <i>KCNQ1</i> were further explored through bioinformatics methods. PCR was used to explore the relative expression of <i>KCNQ1</i> in T2DM patients and the controls.</p><p><strong>Results: </strong>Studies showed that rs163177, rs163184, rs2237895 and rs2283228 on the <i>KCNQ1</i> gene are closely related to the risk of T2DM in Northwest China. MDR results showed that the three-locus model is the best model for T2DM risk assessment, which increases the risk of T2DM. The bioinformatics results showed that <i>KCNQ1</i> closely-acted proteins are mainly involved in signal pathways such as gastric acid secretion and renin secretion. The PCR results showed that, compared with the controls, the expression of <i>KCNQ1</i> was up-regulated in T2DM patients.</p><p><strong>Conclusion: </strong>The results revealed that <i>KCNQ1</i> polymorphism is related to the risk of T2DM in the population of Northwest China and provide a scientific basis for the early screening and prevention of T2DM high-risk populations.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1731-1751"},"PeriodicalIF":1.9,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/59/06/pgpm-14-1731.PMC8725845.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39799391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic Pan-Cancer Analysis of KIF23 and a Prediction Model Based on KIF23 in Clear Cell Renal Cell Carcinoma (ccRCC).","authors":"Xiaojie Bai,&nbsp;Yuanfei Cao,&nbsp;Xin Yan,&nbsp;Kurerban Tuoheti,&nbsp;Guowei Du,&nbsp;Zhao Chen,&nbsp;Huahui Wu,&nbsp;Linfa Guo,&nbsp;Tongzu Liu","doi":"10.2147/PGPM.S337695","DOIUrl":"https://doi.org/10.2147/PGPM.S337695","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to carry out a pan-cancer analysis of kinesin family member 23 (KIF23) and construct a predictive model for the prognosis of clear cell renal cell carcinoma (ccRCC) patients.</p><p><strong>Methods: </strong>We evaluated the differential expression of KIF23 in pan-cancer by The Cancer Genome Atlas (TCGA) and Oncomine database. Then, the correlation between KIF23 with prognosis, clinical grade, stage, immune subtype, tumor mutation burden (TMB), microsatellite instability (MSI) and immune microenvironment was explored by TCGA, an integrated repository portal for tumor-immune system interactions (TISIDB) and cBioPortal. Subsequently, we screened out ferroptosis-related genes (FRGs) related to KIF23 and constructed a risk score model. Univariate Cox analysis was used to determine independent prognostic factors for ccRCC overall survival (OS), and a nomogram was established. Furthermore, gene set enrichment analysis (GSEA) was applied to study the biological functions and pathways of KIF23. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to evaluate the expression of KIF23.</p><p><strong>Results: </strong>KIF23 was highly expressed in most tumors. Further, KIF23 was strongly correlated with prognosis, clinical grade, stage, immune subtype, TMB, MSI and immune microenvironment in different tumors. We found that KIF23 was significantly associated with all aspects of ccRCC. Then, 8 FRGs were identified to construct a risk score model together with KIF23. And a prognostic nomogram prediction model of OS was established. After GSEA analysis, cell cycle, condensed chromosome and other physiological processes were screened out. Finally, qRT-PCR verified the high expression of KIF23 in ccRCC cell lines than normal kidney cell line.</p><p><strong>Conclusion: </strong>KIF23 may act as a pivotal part in occurrence and progression of different tumors. In ccRCC, KIF23 can be a great prognostic biomarker, and the nomogram based on KIF23 may contribute to better treatment plans for ccRCC patients.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1717-1729"},"PeriodicalIF":1.9,"publicationDate":"2021-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f9/a6/pgpm-14-1717.PMC8725058.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39799390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>ADAMTS8</i> Expression is a Potential Prognostic Biomarker for Postoperative Metastasis in Lymph Node-Negative Early-Stage Invasive Breast Carcinoma Patients.","authors":"Yao Li,&nbsp;Xin Yang,&nbsp;Jie Sun,&nbsp;Yangyang Zhao,&nbsp;Qi Zhou,&nbsp;Bin Hua","doi":"10.2147/PGPM.S339919","DOIUrl":"https://doi.org/10.2147/PGPM.S339919","url":null,"abstract":"<p><strong>Purpose: </strong>Invasive breast carcinoma (BC) is the most common malignant breast tumor. Most lymph node-negative (LN<b>-</b>) early-stage BC patients usually have a good prognosis, but 7% of patients still develop metastasis after surgery. It is not yet clear how to screen candidates with poorer prognosis in LN- early-stage patients, so that they can receive intensive therapy. Hence, we expect to identify a prognostic biomarker to assess postoperative metastasis in LN- early-stage BC patients.</p><p><strong>Patients and methods: </strong>Screening and verifying of candidate genes by gene expression profiling of LN- early-stage BC samples (n = 640) from 3 independent public datasets. Univariable and multivariable Cox regression analyses showed the relation between the candidate genes and postoperative metastasis. Distant metastasis-free survival (DMFS) analysis was performed to examine the prognostic significance. Quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to examine <i>ADAMTS8</i> expression and prognostic association in our clinical samples (n = 25).</p><p><strong>Results: </strong>In the discovery cohort (TCGA and GSE20685 datasets), we found that <i>ADAMTS8</i> tend to be low expression in LN- early-stage BC, and low <i>ADAMTS8</i> expression was associated with postoperative metastasis and shortened DMFS. Moreover, the above finding was confirmed in the validation cohort (GSE6538 dataset). Lower <i>ADAMTS8</i> expression was related to poorer prognostic clinical stage and PAM50 subtypes and shorter DMFS. Gene enrichment analysis indicated that <i>ADAMTS8</i> may be correlated with BC metastasis. qRT-PCR assays of our clinical tumor sample showed that patients with low <i>ADAMTS8</i> expression seem to be prone to developing metastasis and have a shorter DMFS time.</p><p><strong>Conclusion: </strong>Our research shows that low <i>ADAMTS8</i> expression is associated with postoperative metastasis and shortened DMFS in LN- early-stage BC patients, which suggests that <i>ADAMTS8</i> may be a potential prognostic marker for postoperative metastasis in LN- early-stage BC patients.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1701-1713"},"PeriodicalIF":1.9,"publicationDate":"2021-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/08/af/pgpm-14-1701.PMC8722701.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39799388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: The EGFR Polymorphism Increased the Risk of Hepatocellular Carcinoma Through the miR-3196-Dependent Approach in Chinese Han Population [Corrigendum].","authors":"","doi":"10.2147/PGPM.S349137","DOIUrl":"https://doi.org/10.2147/PGPM.S349137","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.2147/PGPM.S304524.].</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1715-1716"},"PeriodicalIF":1.9,"publicationDate":"2021-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1a/72/pgpm-14-1715.PMC8724788.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39799389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fragile X Premutation: Medications, Therapy and Lifestyle Advice.","authors":"Deepika Kour Sodhi,&nbsp;Randi Hagerman","doi":"10.2147/PGPM.S338846","DOIUrl":"https://doi.org/10.2147/PGPM.S338846","url":null,"abstract":"<p><p>The fragile X premutation is characterized by 55-200 CGG repeats in the 5' untranslated region of <i>FMR1,</i> whereas full fragile X mutation has greater than 200 repeats and full methylation, which manifests as fragile X syndrome (FXS). The premutation spectrum of clinical involvement includes fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND). In addition, premutation carriers also suffer from various other health problems such as endocrine abnormalities and autoimmune problems. In this paper, we have discussed different health issues faced by the carriers and interventions including medications, therapy and lifestyle changes that could improve their health.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1689-1699"},"PeriodicalIF":1.9,"publicationDate":"2021-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ff/36/pgpm-14-1689.PMC8721286.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39799387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isotretinoin Induced Hyperlipidemia and Impact of Leptin Gene <i>rs</i> 7799039 Polymorphism in Safety of Acne Patients.","authors":"Amal A Mohamed,&nbsp;Alshymaa Hassnine,&nbsp;Amr Elsayed,&nbsp;Mahmoud Montaser,&nbsp;Yasmeen Ismail,&nbsp;Ahmed El-Demery,&nbsp;Eman Sultan,&nbsp;Rania S Abdel Aziz,&nbsp;Eman Eldemiry,&nbsp;Radwa Hagag,&nbsp;Amal A El-Kholy,&nbsp;Eman Salah","doi":"10.2147/PGPM.S341723","DOIUrl":"https://doi.org/10.2147/PGPM.S341723","url":null,"abstract":"<p><strong>Background: </strong>Acne vulgaris (AV) is a chronic inflammatory disease that affects the pilosebaceous unit. Leptin (LEP) gene polymorphisms is associated with higher risk of multiple disorders. Insulin-like growth factor-1 (IGF-1) exerts comedogenic effect by stimulating the sebaceous glands. Isotretinoin is an effective oral therapy for AV with many side effects including hyperlipidemia and increased serum levels of liver enzymes.</p><p><strong>Purpose: </strong>To evaluate the impact of LEP gene rs7799039 polymorphism in acne patients' clinical response lipid profile and liver enzymes following 6 months oral isotretinoin therapy in Egyptian AV patients.</p><p><strong>Methods: </strong>One hundred eligible AV patients received 0.5 mg/kg oral isotretinoin for 6 months. Patients' demographics and clinical data were obtained. Body mass index (BMI), lipid profile, liver enzymes and IGF-1 were measured at baseline and after 6 months of therapy. Genotyping was done for LEP gene <i>rs</i> 7799039.</p><p><strong>Results: </strong>Six month administration of oral isotretinoin in Egyptian AV patients is associated with significantly elevated aspartate transaminase (AST) in CC and AC genotypes (P<0.001). Significant alanine aminotransferase (ALT) elevation was observed in CC, AC and AA genotypes (P <0.001, 0.004, 0.002, respectively). Total cholesterol (TC), triglycerides (TG) and low density lipoprotein (LDL) were elevated significantly P<0.001) in the three genotypes. IGF-1 was decreased significantly in CC and AC genotypes (P<0.001). CC genotype is associated with highest response (P<0.001).</p><p><strong>Conclusion: </strong>LEP rs7799039 gene had an impact on the clinical response, lipid profile and liver enzymes in AV patients treated with oral isotretinoin. LEP rs7799039 CC genotype is predicted to be the treatment candidate for 6 month oral isotretinoin.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1679-1687"},"PeriodicalIF":1.9,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/21/44/pgpm-14-1679.PMC8714009.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39791633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>PFN1</i> Gene Polymorphisms and the Bone Mineral Density Response to Alendronate Therapy in Postmenopausal Chinese Women with Low Bone Mass.","authors":"Jiao Zhao,&nbsp;Li Liu,&nbsp;Shanshan Lv,&nbsp;Chun Wang,&nbsp;Hua Yue,&nbsp;Zhenlin Zhang","doi":"10.2147/PGPM.S344818","DOIUrl":"https://doi.org/10.2147/PGPM.S344818","url":null,"abstract":"<p><strong>Purpose: </strong>Alendronate is a widely used anti-osteoporotic drug. <i>PFN1</i> gene is a newly identified early-onset Paget's disease pathogenic gene. The purpose of this study is to study whether the genetic variations in this gene affect the clinical efficacy of alendronate in postmenopausal Chinese women with low bone mass.</p><p><strong>Patients and methods: </strong>Seven single nucleotide polymorphisms in <i>PFN1</i> gene were genotyped. A total of 500 postmenopausal women with osteoporosis or osteopenia were included. All participants were treated with weekly alendronate 70 mg for 12 months. A total of 466 subjects completed the follow-up. Bone mineral density (BMD) of lumbar spine, femoral neck and total hip were measured at baseline and after treatment.</p><p><strong>Results: </strong>After 12 months of treatment, the BMD of lumbar spine, femoral neck and total hip all increased significantly (all <i>P</i> < 0.001), with an average increase of 4.72 ± 5.31%, 2.08 ± 4.45%, and 2.42 ± 3.46%, respectively. At baseline, there were no significant differences in BMD at lumbar spine, femoral neck and total hip between different genotype groups (<i>P</i> > 0.05). We failed to identify any significant association between the genotypes or haplotypes of <i>PFN1</i> and the BMD response to alendronate therapy.</p><p><strong>Conclusion: </strong>Genetic polymorphisms of <i>PFN1</i> may not be a major contributor to the therapeutic response to alendronate treatment in Chinese women with low bone mass.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1669-1678"},"PeriodicalIF":1.9,"publicationDate":"2021-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ab/8b/pgpm-14-1669.PMC8711734.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39791632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined GSTT1 Null, GSTM1 Null and XPD Lys/Lys Genetic Polymorphisms and Their Association with Increased Risk of Chronic Myeloid Leukemia.","authors":"Ezeldine K Abdalhabib,&nbsp;Denise E Jackson,&nbsp;Badr Alzahrani,&nbsp;Elyasa M Elfaki,&nbsp;Alneil Hamza,&nbsp;Fehaid Alanazi,&nbsp;Elryah I Ali,&nbsp;Abdulrahman Algarni,&nbsp;Ibrahim Khider Ibrahim,&nbsp;Muhammad Saboor","doi":"10.2147/PGPM.S342625","DOIUrl":"https://doi.org/10.2147/PGPM.S342625","url":null,"abstract":"<p><strong>Purpose: </strong>Glutathione <i>S</i>-transferases (GSTT1 and GSTM1) are instrumental in detoxification process of activated carcinogens. Nucleotide excision repair is carried out by DNA helicase encoded by xeroderma pigmentosum group D (XPD) genes and aberrations in the <i>XPD</i> gene predisposes to increased risk of cancer. The present study aimed to investigate GSTT1, GSTM1 and XPD polymorphisms in newly diagnosed chronic myeloid leukemia (CML) patients and to examine the association of these polymorphisms with the risk of developing CML.</p><p><strong>Patients and methods: </strong>This case-control study was carried out from June 2019 to August 2021 involving 150 newly diagnosed patients with CML and an equal number of randomly selected age- and sex-matched healthy individuals. A multiplex-PCR assay was used to genotype GSTT1 null and GSTM1 null polymorphisms. XPD gene polymorphism was detected by PCR-RFLP using predesigned gene-specific primers.</p><p><strong>Results: </strong>GSTT1 and GSTM1 null polymorphisms were detected in 42.7% and 61.3% of cases, respectively, compared to 18% and 35.3% for controls. The combination of both GST null polymorphisms revealed a significant association with CML. Frequencies of XPD Lys751Gln genotypes in cases were 62.7% heterozygous Lys/Gln, 24% homozygous Lys/Lys and 13.3% homozygous Gln/Gln, while in the controls were 74.7%, 20%, and 5.3%, respectively. Significant differences were also noted regarding the combination of GSTT1/GSTM1 null with XPD Lys/Lys, and GSTM1 null with XPD Lys/Lys.</p><p><strong>Conclusion: </strong>In conclusion, GSTT1 null, GSTM1 null and XPD polymorphisms showed positive association with the risk of development of CML. Furthermore, age and gender did not exhibit any association with the studied polymorphisms, while CML phases were associated with GSTT1 null polymorphism.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1661-1667"},"PeriodicalIF":1.9,"publicationDate":"2021-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d6/82/pgpm-14-1661.PMC8710912.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39791631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}