Pharmacogenomics & Personalized Medicine最新文献

{"title":"Identification of a Prognostic Gene Signature Based on Lipid Metabolism-Related Genes in Esophageal Squamous Cell Carcinoma","authors":"Guo-Yi Shen, Peng-Jie Yang, Wen-Shan Zhang, Jun-Biao Chen, Qin-Yong Tian, Yi Zhang, Bater Han","doi":"10.2147/pgpm.s430786","DOIUrl":"https://doi.org/10.2147/pgpm.s430786","url":null,"abstract":"","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135410133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with Protein Tyrosine Phosphatase Non-Receptor Type 11 Gene Mutation","authors":"Rui Huang, Yi-Ting Zhang, Yu Lin, Ru-Li Pang, Zhi Yang, Wei-Hua Zhao","doi":"10.2147/pgpm.s420254","DOIUrl":"https://doi.org/10.2147/pgpm.s420254","url":null,"abstract":"Objective: The purpose of our study was to investigate the clinical characteristics, molecular biological characteristics and prognosis of acute myeloid leukemia (AML) patients with protein tyrosine phosphatase non-receptor type 11 (PTPN11) gene mutation. Methods: The clinical data of 30 newly diagnosed adult AML patients with PTPN11 gene mutation were analyzed retrospectively. Kaplan-Meier and Cox proportional risk regression model were examined for prognostic analysis and prognostic factor screening. Results: High-frequency mutation sites of PTPN11 gene are located in exon 3 of chromosome 12, which are D61 and A72 (16.7%), followed by E76 (13.3%). The median variant allele frequency (VAF) of PTPN11 mutant gene is 18.4%. The patients were divided into two groups according to PTPN11 VAF 35.3% (upper quartile). We observed that the peripheral blood leukocyte count in patients with VAF ≥ 35.3% was significantly higher than patients with VAF < 35.3% (p = 0.019) and also closely related to M5 (p = 0.016) and internal tandem duplication (ITD) of FMS-like tyrosine kinase 3 (FLT3) (FLT3-ITD) mutation (p = 0.048). Taking PTPN11 VAF 20% and 35.3% as the cutoff value, the patients were divided into two groups, and the overall survival and event-free survival (EFS) of the two groups were not significant. Multivariate analysis of Cox risk ratio model showed that white blood cell count and Eastern Cooperative Oncology Group (ECOG) physical status score were independent risk factors affecting the EFS. Conclusion: Our study observed that PTPN11 VAF may not be a prognostic factor in patients with PTPN11 mut AML. Newly diagnosed high white blood cell count and poor performance status were independent risk factors for EFS in PTPN11 mut AML. Keywords: acute myeloid leukemia, PTPN11, mutation, clinical characteristics, prognosis","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135708930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic Artery Infusion Chemotherapy Sequential Hepatic Artery Embolization Combined with Operation in the Treatment of Recurrent Massive Hepatocellular Carcinoma Achieved Pathological Complete Response: A Case Report.","authors":"Junjie Chen, Xiwen Liao, Yining Wu, Shenjian Ou, Wei Qin, Chengkun Yang, Yufeng Tan, Quan Lao, Minhao Peng, Tao Peng, Xinping Ye","doi":"10.2147/PGPM.S426791","DOIUrl":"https://doi.org/10.2147/PGPM.S426791","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) recurrence, which encompasses both true recurrence resulting from cancer spread and de novo tumors developing within the same cancer-prone liver, presents a complication in approximately 70% of cases within a 5-year timeframe. The efficacy of neoadjuvant therapy for recurrence after hepatectomy for hepatocellular carcinoma is still unclear. We report a case of recurrent massive advanced hepatocellular carcinoma with pathological complete remission was treated by continuous hepatic arterial infusion chemotherapy (HAIC) and sequential transcatheter arterial embolization (TAE) combined with secondary operation. One month after resection, the patient recurred (massive type 141mm×76mm). After 4 times of HAIC sequential TAE conversion therapy, the tumor shrank significantly (70mm×29mm), alpha-fetoprotein(AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels decreased significantly, residual liver volume[left half liver accounted for 39.85% of standard liver volume(left half liver + right anterior lobe) accounted for 80.17% of standard liver volume] and Indocyanine green 15-minute retention(ICG R15 8.0%) complies with surgical requirement.The second operation was performed, and the tumor was completely resected after hepatic blood flow occlusion Requirement. The postoperative pathological results showed complete remission (PCR) of the tumor, and no recurrence was found during the follow-up of 16 months. In this case, HAIC sequential TAE conversion therapy has good short-term effect on patients with postoperative recurrence of hepatocellular carcinoma, tumor burden is significantly reduced, the second surgery pathology achieves complete remission, safety and tolerance, it is worthy of study and promotion.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71489378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"rs217727 of lncRNA H19 is Associated with Cervical Cancer Risk in the Chinese Han Population.","authors":"Jie Dai,&nbsp;Shao Zhang,&nbsp;Yuhan Shi,&nbsp;Jinmei Xu,&nbsp;Weipeng Liu,&nbsp;Jia Yang,&nbsp;Li Shi,&nbsp;Zhiling Yan,&nbsp;Chuanyin Li","doi":"10.2147/PGPM.S422083","DOIUrl":"https://doi.org/10.2147/PGPM.S422083","url":null,"abstract":"<p><strong>Background: </strong>Long noncoding RNAs (LncRNAs) have been revealed to involve in cervical cancer (CC) developing. The current study was designed to explore the association of SNPs (rs217727, rs2366152, rs1859168, rs10505477) located in the lncRNA H19, HOTAIR, HOTTIP and CASC8 genes with the risk of CC in a Chinese Han population.</p><p><strong>Methods: </strong>Four SNPs were selected and genotyped in 1426 participants (274 CIN patients, 448 CC patients, and 704 healthy control individuals) using MassArray. The association of these SNPs with susceptibility to CC was evaluated.</p><p><strong>Results: </strong>Significant differences in allelic distribution of rs217727 were observed in the comparison of CC with control (<i>P</i> = 0.001), indicating the risk of rs217727-A allele in CC (OR = 1.33; 95% CI: 1.12-1.58). The inheritance model analysis revealed that 2AA+GA genotype represented a certain risk of CC (<i>P</i> = 0.001, OR = 1.35; 95% CI: 1.13-1.62). The stratified analysis revealed a risk of the rs217727-A allele for cervical squamous cell carcinoma (SCC) (<i>P</i> = 0.002, OR = 1.33; 95% CI: 1.11-1.60).</p><p><strong>Conclusion: </strong>rs217727 in lncRNA H19 exhibited a significant correlation with CC susceptibility, particularly SCC, and A/A genotype of this SNP might present as a risk in CC.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71489379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between <i>CTSK</i> Gene Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women with Low Bone Mineral Density.","authors":"Hu Yuan,&nbsp;Caihong Wang,&nbsp;Li Liu,&nbsp;Chun Wang,&nbsp;Zhenlin Zhang,&nbsp;Shen Qu","doi":"10.2147/PGPM.S425357","DOIUrl":"10.2147/PGPM.S425357","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to explore the association between <i>CTSK</i> polymorphisms and the response to alendronate treatment in postmenopausal Chinese women with low bone mineral density.</p><p><strong>Patients and methods: </strong>In this study, 460 postmenopausal women from Shanghai were included. All of them were treated with weekly oral alendronate 70 mg, daily calcium 600 mg and vitamin D 125 IU for a year. Four tag single nucleotide polymorphisms (SNPs) in <i>CTSK</i> gene were genotyped. Bone mineral densities of lumbar spine (L1-L4), femoral neck and total hip were measured at baseline and after 12 months of treatment, respectively.</p><p><strong>Results: </strong>After 1-year of treatment, there was no significant differences in BMI between baseline and follow-up. After alendronate treatment, the BMD of L1-4, femoral neck and total hip all increased significantly (all <i>P</i> < 0.001), with average increases of 4.33 ± 6.42%, 1.85 ± 4.20%, and 2.36 ± 3.79%, respectively. There was no significant difference in BMD at L1-L4, the femoral neck and total hip between different genotype groups at baseline (<i>P</i>>0.05). After 1-year treatment with alendronate, rs12746973 and rs10847 were associated with the % change of BMD at L1-L4 (<i>P</i>=0.038) and % change of BMD at femoral neck (<i>P</i>=0.038), respectively. Furthermore, rs10847 was associated with BMD response at femoral neck (<i>P</i>=0.013). However, the associations were not significant after Bonferroni correction.</p><p><strong>Conclusion: </strong>We concluded that the common variations of <i>CTSK</i> gene were potentially associated with the therapeutic response to alendronate treatment in Chinese women with low bone mineral density. However, further validation is needed.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case Report of Cardiofaciocutaneous Syndrome with MAP2K1 Pathogenic Variant [Letter].","authors":"Abdul Hadi Furqoni,&nbsp;Indah Fajarwati,&nbsp;Anna Lystia Poetranto","doi":"10.2147/PGPM.S442628","DOIUrl":"10.2147/PGPM.S442628","url":null,"abstract":"","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microarray Expression Profile and Bioinformatic Analysis of Circular RNA in Human Arteriosclerosis Obliterans.","authors":"Yu Zhou,&nbsp;Huoying Cai,&nbsp;Lin Huang,&nbsp;Mingshan Wang,&nbsp;Ruiming Liu,&nbsp;Siwen Wang,&nbsp;Yuansen Qin,&nbsp;Chen Yao,&nbsp;Zuojun Hu","doi":"10.2147/PGPM.S424359","DOIUrl":"https://doi.org/10.2147/PGPM.S424359","url":null,"abstract":"<p><strong>Background: </strong>Arteriosclerosis obliterans (ASO) is the leading cause of nontraumatic lower-extremity amputations. Multiple researches have suggested that circular RNAs (circRNAs) played vital regulatory functions in cancer and cardiovascular disease. Nevertheless, the underlying effect and pathological mechanism of circRNAs in the formation and progression of ASO are still indistinct.</p><p><strong>Methods and results: </strong>This study used microarray analysis to investigate the expression portrait of circRNAs in normal lower extremity arteries and ASO arteries. Bioinformatics analysis was conducted using the KEGG database to study the enrichment of differentially expressed circRNAs (DE circRNAs) and predict their functions. The accuracy of microarray assay was verified by evaluating expression of the top 5 upregulated and 5 downregulated circRNAs (raw density of normal group ≥200) using RT-qPCR. A circRNA-miRNA-mRNA interaction network was further predicted using software. Compared to the normal lower extremity group, the ASO arteries with HE and EVG staining presented hyperplastic fibrous membrane and luminal stenosis. A total of 12,735 circRNAs were identified, including 1196 DE circRNAs with 276 upregulated and 920 downregulated in ASO group based on |log2(FC)| > 1 and padj < 0.05. Among selected 10 circRNAs, RT-qPCR confirmed that hsa_circ_0003266, hsa_circ_0118936 and hsa_circ_0067161 were upregulated while hsa_circ_0091934 and hsa_circ_0092022 were downregulated in ASO group (<i>p</i> < 0.05). GO analysis presented that the DE circRNAs were primarily enriched in protein binding, intracellular part and organelle organization. KEGG pathway analysis indicated that MAPK signaling pathway, human T-cell leukemia virus 1 infection, proteoglycans in cancer were associated with the DE circRNAs. The circRNA-miRNA-mRNA interactive network revealed that both mRNAs and miRNAs linked to circRNAs played an indispensable role in ASO.</p><p><strong>Conclusion: </strong>This study described the expression portrait of circRNAs in human ASO arteries, and revealed the molecular background for further investigations of the circRNA regulatory mechanism in the formation and progression of ASO.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10612483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homocysteine Reduction for Stroke Prevention: Regarding the Recent AHA/ASA 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack.","authors":"Craig Brown,&nbsp;Jianhua Wang,&nbsp;Hong Jiang,&nbsp;Merrill F Elias","doi":"10.2147/PGPM.S426421","DOIUrl":"10.2147/PGPM.S426421","url":null,"abstract":"<p><p>Reduction of secondary ischemic stroke risk following an initial stroke is an important goal. The 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack assembles opportunities for up to 80% secondary stroke reduction. Homocysteine reduction was not included in the recommendations. The reduction of homocysteine with low doses of folic acid has been shown to reduce ischemic stroke and all stroke. This has been obscured by studies using high doses of folic acid and cyanocobalamin in patients with renal failure and Methylenetetrahydrofolate reductase (MTHFR) polymorphisms. The confounding impacts of high dose folic acid and cyanocobalamin toxicity in renal failure and MTHFR C677T subgroups are discussed. New studies show that their toxicity is due to non-bioequivalence to the natural dietary forms, L-methylfolate and methylcobalamin. Low doses of folic acid and cyanocobalamin are safer than high doses for these subpopulations. Even lower toxicity with greater effectiveness for reducing homocysteine is seen with L-methylfolate and methylcobalamin, which are safe at high doses. Retinal vascular imaging is a noninvasive method for evaluating central nervous system (CNS) microangiopathy. A formulation containing l-methylfolate and methylcobalamin has been shown to reduce homocysteine and increase perfusion in diabetic retinopathy. This supports homocysteine intervention for CNS ischemia. Future ischemic stroke intervention studies could benefit from monitoring retinal perfusion to estimate the impact of risk reduction strategies. The omission of a recommendation for homocysteine and secondary stroke reduction through the use of B vitamins should be reconsidered in light of re-analysis of major B vitamin intervention studies and new technologies for monitoring CNS perfusion. We recommend revision of the 2021 Guideline to include homocysteine reduction with low doses of folic acid and cyanocobalamin, or better yet, L-methylfolate and methylcobalamin, making a good clinical guideline better.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ee/88/pgpm-16-895.PMC10559895.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41174232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of CYP450 Enzymes and ABCB1 Polymorphisms on Clopidogrel Response in Moroccan Patients with Acute Coronary Syndromes.","authors":"Ismail Mouhrach,&nbsp;Laila Bouguenouch,&nbsp;Adil Kamal,&nbsp;Abbassi Meriame,&nbsp;Nada El Khorb,&nbsp;Mohammed El Azami El Idrissi,&nbsp;Hafid Akoudad,&nbsp;Hicham Bekkari","doi":"10.2147/PGPM.S390092","DOIUrl":"10.2147/PGPM.S390092","url":null,"abstract":"<p><strong>Introduction: </strong>Clopidogrel is an antiplatelet prodrug primarily prescribed to prevent or treat acute coronary syndrome (ACS) or acute ischemic stroke (IS), polymorphisms of genes encoding cytochrome P-450 (CYP) and P-glycoprotein transporter, could affect the efficiency of clopidogrel absorption and biotransformation, especially during the first critical hours following its administration.</p><p><strong>Methods: </strong>The present study was designed to investigate the potential association of clopidogrel responsiveness and 14 polymorphisms in the genes encoding the CYPs (CYP2C9, 2C19, 3A4, 3A5, 1A2, and 2B6), the ATP binding cassette subfamily B member 1 (ABCB1). Platelet aggregation activity was measured after 8h of 300mg clopidogrel administration for fifty-five ACS patients.</p><p><strong>Results: </strong>There was no significant association between polymorphism of the studied CYPs and clopidogrel responsiveness (P>0.05). The frequency of the ABCB1 3435 T allele in clopidogrel non-responders was higher (78.9%) compared to responders (52.8%), but this difference was not significant (P=0.057). Demographic characteristics, comorbidities, concomitant treatments were not associated with clopidogrel response.</p><p><strong>Discussion: </strong>There was no effect of the studied genetic variations and demographic factors on the platelet activity of clopidogrel in Moroccan ACS patients.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cb/2d/pgpm-16-901.PMC10557961.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41160410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel <i>MYBPC3</i> Mutations in Indian Population with Cardiomyopathies.","authors":"Deepa Selvi Rani,&nbsp;Apoorva Kasala,&nbsp;Perundurai S Dhandapany,&nbsp;Uthiralingam Muthusami,&nbsp;Sreejith Kunnoth,&nbsp;Andiappan Rathinavel,&nbsp;Dharma Rakshak Ayapati,&nbsp;Kumarasamy Thangaraj","doi":"10.2147/PGPM.S407179","DOIUrl":"https://doi.org/10.2147/PGPM.S407179","url":null,"abstract":"<p><strong>Background: </strong>Mutations in Myosin Binding Protein C (<i>MYBPC3</i>) are one of the most frequent causes of cardiomyopathies in the world, but not much data are available in India.</p><p><strong>Methods: </strong>We carried out targeted direct sequencing of <i>MYBPC3 </i>in 115 hypertrophic (HCM) and 127 dilated (DCM) cardiomyopathies against 197 ethnically matched healthy controls from India.</p><p><strong>Results: </strong>We detected 34 single nucleotide variations in <i>MYBPC3</i>, of which 19 were novel. We found a splice site mutation [(IVS6+2T) T>G] and 16 missense mutations in Indian cardiomyopathies [5 in HCM; E258K, T262S, H287L, R408M, V483A: 4 in DCM; T146N, V321L, A392T, E393K and 7 in both HCM and DCM; L104M, V158M, S236G, R272C, T290A, G522E, A626V], but those were absent in 197 normal healthy controls. Interestingly, we found 7 out of 16 missense mutations (V158M, E258K, R272C, A392T, V483A, G522E, and A626V) in <i>MYBPC3</i> were altering the evolutionarily conserved native amino acids, accounted for 8.7% and 6.3% in HCM and DCM, respectively. The bioinformatic tools predicted that those 7 missense mutations were pathogenic. Moreover, the co-segregation of those 7 mutations in families further confirmed their pathogenicity. Remarkably, we also identified compound mutations within the <i>MYBPC3</i> gene of 6 cardiomyopathy patients (5%) with more severe disease phenotype; of which, 3 were HCM (2.6%) [(1. K244K + E258K + (IVS6+2T) T>G); (2. L104M + G522E + A626V); (3. P186P + G522E + A626V]; and 3 were DCM (2.4%) [(1. 5'UTR + A392T; 2. V158M+G522E; and 3.V158M + T262T + A626V].</p><p><strong>Conclusion: </strong>The present comprehensive study on <i>MYBPC3</i> has revealed both single and compound mutations in <i>MYBPC3</i> and their association with disease in Indian Population with Cardiomyopathies. Our findings may perhaps help in initiating diagnostic strategies and eventually recognizing the targets for therapeutic interventions.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c0/7a/pgpm-16-883.PMC10518145.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}