Pharmacogenomics and Personalized Medicine最新文献

{"title":"Prescription Advice Based on Data of Drug-Drug-Gene Interaction of Patients with Polypharmacy.","authors":"Sandro Salamone,&nbsp;Sara Spirito,&nbsp;Maurizio Simmaco,&nbsp;Marius Unger,&nbsp;Saskia Preissner,&nbsp;Björn-Oliver Gohlke,&nbsp;Andreas Eckert,&nbsp;Robert Preissner","doi":"10.2147/PGPM.S368606","DOIUrl":"https://doi.org/10.2147/PGPM.S368606","url":null,"abstract":"<p><strong>Purpose: </strong>Pharmacogenetic counselling is a complex task and requires the efforts of an interdisciplinary team, which cannot be implemented in most cases. Therefore, simple rules could help to minimize the risk of medications incompatible with each other or with frequent genetic variants.</p><p><strong>Patients and methods: </strong>One hundred and eighty-four multi-morbid Caucasian patients suffering from side effects or inefficient therapy were enrolled and genotyped. Their medication was analyzed by a team of specialists using Drug-PIN^® (medication support system) and individual recommendations for 34 drug classes were generated.</p><p><strong>Results: </strong>In each of the critical drug classes, 50% of the drugs cannot be recommended to be prescribed in typical drug cocktails. PPIs and SSRI/SNRIs represent the most critical drug classes without showing a single favorable drug. Among the well-tolerated drugs (not recommended for less than 5% of the patients) are metamizole, celecoxib, olmesartan and famotidine. For each drug class, a ranking of active ingredients according to their suitability is presented.</p><p><strong>Conclusion: </strong>Genotyping and its profound analysis are not available in many settings today. The consideration of frequent alterations of metabolic elimination routes and drug-drug-gene interactions by using simple rankings can help to avoid many incompatibilities, side effects and inefficient therapies.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"765-773"},"PeriodicalIF":1.9,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/8f/pgpm-15-765.PMC9394521.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40637266","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":"Genome-Wide Association Study on the Hematological Phenotypic Characteristics of the Han Population from Northwest China.","authors":"Wei Yang,&nbsp;Xue He,&nbsp;Yuying Yao,&nbsp;Hongyan Lu,&nbsp;Yuliang Wang,&nbsp;Zhanhao Zhang,&nbsp;Yuhe Wang,&nbsp;Li Wang,&nbsp;Yongjun He,&nbsp;Dongya Yuan,&nbsp;Tianbo Jin","doi":"10.2147/PGPM.S361809","DOIUrl":"https://doi.org/10.2147/PGPM.S361809","url":null,"abstract":"<p><strong>Background: </strong>Hematological characteristics have positive reference value as clinical indicators in the evaluation of various diseases. The purpose of this study was to determine the gene loci associated with 20 hematological phenotypes in the Han population from northwest China.</p><p><strong>Methods: </strong>A genome-wide association study (GWAS) was conducted on hematological indicators of 1005 Han people from northwest China. Genotyping was performed with a GeneTitan multichannel instrument and Axiom Analysis Suite 6.0. Using the 1000 Genomes Project (phase 3) as a reference, haplotype imputation was performed with IMPUTE2. SNVs (single nucleotide variants) significantly associated with hematological phenotypes were identified. The top SNV (<i>p</i> < 5E-7) was then selected for replication detection.</p><p><strong>Results: </strong>Ninety genetic variations identified in the GWAS were significantly associated with hematological indicators. Among them, only rs35289401 (CCDC157) was significantly associated (genome-wide) with red blood cell distribution width (RDW) (<i>p</i> = 4.21E-08). The fourteen top SNVs were selected for replication verification and were significantly associated with hematological phenotypes. However, only HBS1 L-MYB rs1331309 was significantly associated with the mean hemoglobin content (<i>p</i> = 6.42E-07). We also found that the mean corpuscular hemoglobin (MCH) level in the rs1331309 GG/GT genotype was significantly higher than that in the TT genotype (<i>p</i> = 0.023).</p><p><strong>Conclusion: </strong>The GWAS identified a total of 90 genetic variants significantly associated with hematological phenotypic indicators. In particular, rs1331309 (HBS1 L-MYB) is expected to be a biomarker for monitoring the dynamics of MCH levels. This study provides a reference for related studies on the genetic structure of hematological characteristics. It provides a valuable reference for the clinical diagnosis or prediction of a variety of diseases.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"743-763"},"PeriodicalIF":1.9,"publicationDate":"2022-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/77/pgpm-15-743.PMC9357418.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40596263","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":"Cuproptosis-Related Gene - <i>SLC31A1, FDX1</i> and <i>ATP7B</i> - Polymorphisms are Associated with Risk of Lung Cancer.","authors":"Yuhui Yun,&nbsp;Yun Wang,&nbsp;Ende Yang,&nbsp;Xin Jing","doi":"10.2147/PGPM.S372824","DOIUrl":"https://doi.org/10.2147/PGPM.S372824","url":null,"abstract":"<p><strong>Background: </strong>Cuproptosis is a novel copper-dependent cell death, and the copper level was increased in lung cancer patients. However, few studies evaluated the association between single-nucleotide polymorphisms (SNPs) in cuproptosis-related genes and lung cancer risk.</p><p><strong>Methods: </strong>Six SNPs of the <i>SLC31A1, FDX1</i> and <i>ATP7B</i> genes were genotyped in a case-control cohort including 650 lung cancer cases and 650 controls using the MassARRAY platform.</p><p><strong>Results: </strong>The minor alleles of <i>SLC31A1</i>-rs10981694 and <i>FDX1</i>-rs10488764 were associated with an increased risk of lung cancer (rs10981694: OR=1.455, 95% CI: 1.201-1.763, <i>p</i><0.001; rs10488764: OR=1.483, 95% CI: 1.244-1.768, <i>p</i><0.001). In contrast, the minor alleles of rs9535826 and rs9535828 in <i>ATP7B</i> were related to a decreased risk of the disease (rs9535826: OR=0.714, 95% CI: 0.608-0.838 <i>p</i><0.001; rs9535828: OR=0.679, 95% CI: 0.579-0.796, <i>p</i><0.001). The frequencies of rs10981694-TG/GG and rs10488764-GA/AA genotypes were significantly higher in lung cancer cases than that in controls, making them risk genotypes for the disease (<i>p</i> < 0.001); while the rs9535826-TG/GG and rs9535828-GA/AA genotypes were protective genotypes and associated with a reduced risk of the disease (<i>p</i><0.001). Genetic model evaluation revealed that <i>SLC31A1</i>-rs10981694 and <i>FDX1</i>-rs10488764 were associated with a growing risk of lung cancer in dominant, recessive and log-additive models (<i>p</i><0.001). Moreover, rs9535826 and rs9535828 in <i>ATP7B</i> were related to a declining risk of the disease in three genetic models (<i>p</i><0.001). In addition, stratification analysis showed that <i>FDX1</i>-rs10488764 was risk variant for lung cancer in both smokers and nonsmokers, and was associated with risk of each pathological type of lung cancer (<i>p</i><0.008).</p><p><strong>Conclusion: </strong>The results shed new light on the correlation between cuproptosis-related genes and risk of lung cancer.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"733-742"},"PeriodicalIF":1.9,"publicationDate":"2022-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0e/00/pgpm-15-733.PMC9342429.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40598924","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 Study on the Molecular Mechanism of High Altitude Heart Disease in Children.","authors":"Qu-Zhen Tashi,&nbsp;Sang-Bu Tsering,&nbsp;Na-Ni Zhou,&nbsp;Yi Zhang,&nbsp;Yu-Juan Huang,&nbsp;Jia Jia,&nbsp;Ting-Jun Li","doi":"10.2147/PGPM.S356206","DOIUrl":"https://doi.org/10.2147/PGPM.S356206","url":null,"abstract":"<p><strong>Objective: </strong>High altitude heart disease (HAHD) is a common pediatric disease in high altitude areas. It usually occurs in people who have lived for a long time or have lived for more than 2500m above sea level. Its common inducement is respiratory tract infection. The clinical differential diagnosis is difficult because the symptoms of HAHD are similar to those of congenital heart disease; Due to the limitation of medical conditions, many patients are in the state of losing follow-up or not seeking medical treatment, resulting in poor prognosis of HAHD and becoming a high-altitude disease with high mortality. Clarifying the molecular mechanism of HAHD, developing early molecular screening technology and accurate treatment methods of HAHD are the key to improve the ability of prevention and treatment of HAHD.</p><p><strong>Methods: </strong>First, the literature in the PubMed and CNKI databases were screened based on keywords and abstracts. Then, the literature for the study was identified based on the fitness between the content of the literature, the research objectives, and the timeliness of the literature. Finally, a systematic molecular mechanism of HAHD was established by investigating the literature and sorting out the genetic adaptations of Tibetan populations compared with low-altitude populations that migrated to the plateau.</p><p><strong>Results: </strong>With the investigation of the 48 papers screened, it was found that genes capable of enhancing the hypoxic ventilatory response and resistance to pulmonary hypertension were all correlated with the hypoxia-inducible factor (HIF) pathway, consisting mainly of three pathways, HIF-1α, HIF-2α, and NO.</p><p><strong>Conclusion: </strong>The low prevalence of HAHD in Tibetan aboriginal children was mainly due to the genetic adaptation of the Tibetan population to the high altitude environment, which coordinated the cellular response to hypoxia by regulating the downstream hypoxia control genes in the HIF pathway.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"721-731"},"PeriodicalIF":1.9,"publicationDate":"2022-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3d/f8/pgpm-15-721.PMC9316483.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40554648","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":"Multiple Recurrent Copy Number Variations (CNVs) in Chromosome 22 Including 22q11.2 Associated with Autism Spectrum Disorder.","authors":"Safiah Alhazmi,&nbsp;Maryam Alzahrani,&nbsp;Reem Farsi,&nbsp;Mona Alharbi,&nbsp;Khloud Algothmi,&nbsp;Najla Alburae,&nbsp;Magdah Ganash,&nbsp;Sheren Azhari,&nbsp;Fatemah Basingab,&nbsp;Asma Almuhammadi,&nbsp;Amany Alqosaibi,&nbsp;Heba Alkhatabi,&nbsp;Aisha Elaimi,&nbsp;Mohammed Jan,&nbsp;Hesham M Aldhalaan,&nbsp;Aziza Alrafiah,&nbsp;Aisha Alrofaidi","doi":"10.2147/PGPM.S366826","DOIUrl":"https://doi.org/10.2147/PGPM.S366826","url":null,"abstract":"<p><strong>Introduction: </strong>Autism spectrum disorder (ASD) is a developmental disorder that can cause substantial social, communication, and behavioral challenges. Genetic factors play a significant role in ASD, where the risk of ASD has been increased for unclear reasons. Twin studies have shown important evidence of both genetic and environmental contributions in ASD, where the level of contribution of these factors has not been proven yet. It has been suggested that copy number variation (CNV) duplication and the deletion of many genes in chromosome 22 (Ch22) may have a strong association with ASD. This study screened the CNVs in Ch22 in autistic Saudi children and assessed the candidate gene in the CNVs region of Ch22 that is most associated with ASD.</p><p><strong>Methods: </strong>This study included 15 autistic Saudi children as well as 4 healthy children as controls; DNA was extracted from samples and analyzed using array comparative genomic hybridization (aCGH) and DNA sequencing.</p><p><strong>Results: </strong>The aCGH detected (in only 6 autistic samples) deletion and duplication in many regions of Ch22, including some critical genes. Moreover, DNA sequencing determined a genetic mutation in the TBX1 gene sequence in autistic samples. This study, carried out using aCGH, found that six autistic patients had CNVs in Ch22, and DNA sequencing revealed mutations in the TBX1 gene in autistic samples but none in the control.</p><p><strong>Conclusion: </strong>CNV deletion and the duplication of the TBX1 gene could be related to ASD; therefore, this gene needs more analysis in terms of expression levels.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"705-720"},"PeriodicalIF":1.9,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/5a/pgpm-15-705.PMC9309317.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40554076","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":"Identification of a Novel <i>OFD1</i> Variant in a Patient with Primary Ciliary Dyskinesia.","authors":"Binyi Yang,&nbsp;Cheng Lei,&nbsp;Danhui Yang,&nbsp;Chenyang Lu,&nbsp;Yingjie Xu,&nbsp;Lin Wang,&nbsp;Ting Guo,&nbsp;Rongchun Wang,&nbsp;Hong Luo","doi":"10.2147/PGPM.S365740","DOIUrl":"https://doi.org/10.2147/PGPM.S365740","url":null,"abstract":"<p><strong>Background: </strong><i>OFD1</i> encodes a protein with 1012 amino acids, which is a component of basal bodies and centrioles, essential for cilia biogenesis. <i>OFD1</i> was reported to be associated with X-chromosome linked dysmorphology syndrome in early studies and recent studies reported a few cases with primary ciliary dyskinesia (PCD) caused by <i>OFD1</i> deficiency.</p><p><strong>Case presentation: </strong>We report a 31-year-old man who suffered from recurrent respiratory infections with typical manifestations of primary ciliary dyskinesia. In addition to respiratory manifestations, the patient also had situs inversus, obesity, gastroesophageal reflux, and hearing impairment. Clubbing fingers and mild streblomicrodactyly were also observed.</p><p><strong>Examination result: </strong>We performed whole-exome sequencing to identify a novel variant c.2795delA:p.(Lys932Argfs*3) in <i>OFD1</i>. The hemizygous variant was predicted to be likely pathogenic by bioinformatic analysis software and ACMG guideline. High-speed video microscopy (HSVM), transmission electron microscopy (TEM), and immunofluorescence were performed to analyze the respiratory cilia. A high beating frequency and a stiff beating pattern were observed under HSVM, while there were no significant abnormalities in TEM and immunofluorescence. The sperm flagella examinations were also generally normal.</p><p><strong>Conclusion: </strong>Our study identified a novel frameshift variant in <i>OFD1</i> causing PCD, enriched the genetic spectrum of <i>OFD1</i> variants, and verified that <i>OFD1</i> mutation can lead to only a PCD characteristic phenotype, while other <i>OFD1</i>-associated syndromic symptoms such as dysmorphic features and renal symptoms were not present.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"697-704"},"PeriodicalIF":1.9,"publicationDate":"2022-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/67/55/pgpm-15-697.PMC9285985.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40514487","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":"The Impact of Pharmacogenetics on Pharmacokinetics and Pharmacodynamics in Neonates and Infants: A Systematic Review.","authors":"Nadir Yalçin,&nbsp;Robert B Flint,&nbsp;Ron H N van Schaik,&nbsp;Sinno H P Simons,&nbsp;Karel Allegaert","doi":"10.2147/PGPM.S350205","DOIUrl":"https://doi.org/10.2147/PGPM.S350205","url":null,"abstract":"<p><p>In neonates, pharmacogenetics has an additional layer of complexity. This is because in addition to genetic variability in genes that code for proteins relevant to clinical pharmacology, there are rapidly maturational changes in these proteins. Consequently, pharmacotherapy in neonates has unique challenges. To provide a contemporary overview on pharmacogenetics in neonates, we conducted a systematic review to identify, describe and quantify the impact of pharmacogenetics on pharmacokinetics and -dynamics in neonates and infants (PROSPERO, CRD42022302029). The search was performed in Medline, Embase, Web of Science and Cochrane, and was extended by a PubMed search on the 'top 100 Medicines' (medicine + newborn/infant + pharmacogen*) prescribed to neonates. Following study selection (including data in infants, PGx related) and quality assessment (Newcastle-Ottawa scale, Joanna Briggs Institute tool), 55/789 records were retained. Retained records relate to metabolizing enzymes involved in phase I [cytochrome P450 (CYP1A2, CYP2A6, CYP2B6, CYP2C8/C9/C18, CYP2C19, CYP2D6, CYP3A5, CYP2E1)], phase II [glutathione-S-transferases, N-acetyl transferases, UDP-glucuronosyl-transferase], transporters [ATP-binding cassette transporters, organic cation transporters], or receptor/post-receptor mechanisms [opioid related receptor and post-receptor mechanisms, tumor necrosis factor, mitogen-activated protein kinase 8, vitamin binding protein diplotypes, corticotrophin-releasing hormone receptor-1, nuclear receptor subfamily-1, vitamin K epoxide reductase complex-1, and angiotensin converting enzyme variants]. Based on the available overview, we conclude that the majority of reported pharmacogenetic studies explore and extrapolate observations already described in older populations. Researchers commonly try to quantify the impact of these polymorphisms in small datasets of neonates or infants. In a next step, pharmacogenetic studies in neonatal life should go beyond confirmation of these associations and explore the impact of pharmacogenetics as a covariate limited to maturation of neonatal life (ie, fetal malformations, breastfeeding or clinical syndromes). The challenge is to identify the specific factors, genetic and non-genetic, that contribute to the best benefit/risk balance.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"675-696"},"PeriodicalIF":1.9,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/14/pgpm-15-675.PMC9252316.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40566078","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":"Impact of <i>HOXB4</i> and <i>PRDM16</i> Gene Expressions on Prognosis and Treatment Response in Acute Myeloid Leukemia Patients.","authors":"Yomna M El-Meligui,&nbsp;Naglaa M Hassan,&nbsp;Amira B Kassem,&nbsp;Nora A Gouda,&nbsp;Marwa Mohanad,&nbsp;Manal A Hamouda,&nbsp;Ahmad Salahuddin","doi":"10.2147/PGPM.S368640","DOIUrl":"https://doi.org/10.2147/PGPM.S368640","url":null,"abstract":"<p><strong>Introduction: </strong>Acute myeloid leukemia (AML) is the most common type of leukemia among adults and is characterized by various genetic abnormalities. <i>HOXB4</i> and <i>PRDM16</i> are promising markers of AML. Our objective is to assess the potential roles of <i>HOXB4</i> and <i>PRDM16</i> as prognostic and predictive markers in newly diagnosed AML patients and determine the correlation between their expressions and other prognostic markers as <i>FLT3-ITD, NPM1 exon 12</i> mutations, response to treatment, and patient's survival.</p><p><strong>Methods: </strong>This study included 83 de novo AML adult patients. All patients were subjected to clinical, morphological, cytochemical, and molecular analysis to detect <i>HOXB4</i> and <i>PRDM16</i> gene expressions and <i>FLT3-ITD, NPM1 exon 12</i> mutations.</p><p><strong>Results: </strong>The results showed that a low expression of <i>HOXB4</i> was found in 31.3% of AML patients, whereas a high expression of <i>PRDM16</i> was evident in 33.8% of AML patients. <i>FLT3-ITD</i> mutations were detected in 6 patients (7.2%), while <i>NPM1 exon 12</i> mutations were detected in 7 patients (19.4%) out of 36 patients with intermediate genetic risk. Out of the 50 patients who achieved complete remission (CR), relapse occurred in 16% of the cases. Low expression of <i>HOXB4</i> and high expression of <i>PRDM1</i>6 were associated with CR of 32% and 28%, respectively, and a short overall survival (OS) and disease-free survival (DFS).</p><p><strong>Conclusion: </strong>Further larger study should be conducted to verify that high <i>PRDM16</i> and low <i>HOXB4</i> gene expressions could be used as a poor prognostic predictor for AML. The correlation between <i>PRDM16</i> and <i>HOXB4</i> gene expressions and <i>FLT3-ITD</i> and <i>NPM1 exon 12</i> mutations might have a role on CR, relapse, OS, and, however, this should be clarified in analysis with a larger number of samples.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"663-674"},"PeriodicalIF":1.9,"publicationDate":"2022-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/0e/pgpm-15-663.PMC9241994.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40558915","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":"Effect of Apolipoprotein E ε4 Allele on the Progression of Carotid Atherosclerosis Through Apolipoprotein Levels.","authors":"Wenbing Ma,&nbsp;Liting Zhang,&nbsp;Lei Luo,&nbsp;Suya Zhang,&nbsp;Shuang Yang,&nbsp;Hongping Yao,&nbsp;Lei Zhang,&nbsp;Xiaoyun Lu,&nbsp;Weiyi Feng","doi":"10.2147/PGPM.S367471","DOIUrl":"https://doi.org/10.2147/PGPM.S367471","url":null,"abstract":"<p><strong>Background: </strong>The apolipoprotein E (ApoE) genetic variation may be involved in the development of Carotid Atherosclerosis (CAS) disease. So far, few data are available on the role of ApoE isoforms in CAS. The association between this ApoE genotype and CAS remains controversial. The aim of this study was to investigate ApoE gene polymorphism in relation to CAS and the relationships between ApoE gene polymorphism and plasma lipid levels in the ShaanXi Han populations.</p><p><strong>Patients and methods: </strong>The study group enrolled 399 CAS participants and 399 non-CAS controls. ApoE gene polymorphisms were determined by Polymerase chain reaction and hybridization.</p><p><strong>Results: </strong>The ε3/ε4 genotype and ε4 allele in patients with CAS were significantly higher than control participants. In stratified analyses by age and sex, the elevated risk conferred by ɛ4 allele was evident in adults under 60 years old, but not in adults over 60 years old, females and males. ε4 carriers had significantly elevated ApoB and ApoB/ApoA and decreased ApoE levels than ε2 carriers in CAS patients. After adjusting for confounding factors, hypertension, ApoA-I, low density lipoprotein cholesterol (LDL-C), triglycerides (TG) and ε4 allele were significant independent risk factor for CAS. ApoE-ε4 allele was associated with a nearly 1.5-fold increased risk of CAS.</p><p><strong>Conclusion: </strong>This study provides convincing evidence that ε4 allele, hypertension, ApoA-I, LDL-C and TG levels are independent risk factor for CAS in the ShaanXi Han populations. ApoE polymorphism was associated with CAS and this association was partly mediated through blood lipids. Also, the clinical use of genomic data may become useful in optimizing individual preventative and therapeutic strategies.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"653-661"},"PeriodicalIF":1.9,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/39/00/pgpm-15-653.PMC9233493.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40404700","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":"Inducible Nitric Oxide Synthase iNOS-954-G>C and Ex16+14-C>T Gene Polymorphisms and Susceptibility to Vitiligo in the Saudi Population.","authors":"Fahad Al-Harthi,&nbsp;Ghaleb Bin Huraib,&nbsp;Md Mustafa,&nbsp;Yasser Al-Qubaisy,&nbsp;Naif Al-Nomair,&nbsp;Nour Abdurrahman,&nbsp;Abdulrahman Al-Asmari","doi":"10.2147/PGPM.S344415","DOIUrl":"https://doi.org/10.2147/PGPM.S344415","url":null,"abstract":"<p><strong>Objective: </strong>Vitiligo is an acquired pigmentary skin disorder with regional disappearance of melanocytes. Multigenic inheritance has been proposed in the pathogenesis of vitiligo. The present study aimed to investigate the possible association of inducible nitric oxide synthase polymorphisms iNOS-954-G/C (rs1800482 G>C) and iNOS-Ex16+14-C/T (rs2297518 C>T) with vitiligo in the Saudi population, if any.</p><p><strong>Methods: </strong>We included 120 vitiligo cases and an equal number of age matched healthy controls. Polymerase chain reaction with restriction fragment length polymorphism method was used for the analysis of genetic polymorphisms.</p><p><strong>Results: </strong>The heterozygous (GC), (GC + CC) combined genotype and variant allele; C allele of rs1800482 G>C were associated significantly (<i>p</i> < 0.005, after Bonferroni correction) with increased risk of vitiligo (OR = 3.46, 95% CI = 1.99-6.01, <i>p</i> = 0.001), (OR = 3.30, 95% CI= 1.93-5.65, <i>p</i> = 0.001) and (OR = 1.94, 95% CI = 1.31-2.87, <i>p</i> = 0.001) respectively. When GC genotype of rs1800482 G>C was co-inherited with common genotype (CC) and heterozygous genotype (CT) of rs2297518 C>T, the risk of vitiligo was significantly increased ((OR = 4.51, 95% CI = 2.18-9.33, <i>p</i> = 0.001) and (OR = 3.60, 95% CI = 1.61-8.01, <i>p</i> = 0.001)) respectively. None of the rs1800482 G>C and rs2297518 C>T genotypes and alleles have been associated with non-segmental vitiligo in terms of gender, age of onset, and types of vitiligo.</p><p><strong>Conclusion: </strong>The heterozygous (GC), (GC+CC) combined genotype and variants allele; C allele of rs1800482 G>C, may cause overproduction of NO, which has been linked to melanocyte loss by increasing oxidative stress and decreasing melanocyte adhesion to the extracellular matrix components, and thus could be an associative risk factor for vitiligo.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"603-612"},"PeriodicalIF":1.9,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/56/db/pgpm-15-603.PMC9205318.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40059101","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}