Impact Of Gene Polymorphisms Research Articles

Impact of Gene Polymorphism on Pharmacokinetics and Pharmaco-dynamics of Calcium Channel Blockers: A Narrative Review

A class of drugs known as calcium channel blockers (CCBs) is used to treat hypertension, angina, and arrhythmias. There are two subcategories of this medication class: dihydropyridines and non-dihydropyridines. Studies on CYP3A5*3, AGTR1 rs275653, ABCB1 (MDR1) rs1045642, and POR*28 A503V have all investigated the effects of SNPs on CCBs. This study will carry out more research to ascertain which SNPs have the most influence on the effectiveness of CCBs. The narrative reviews in this article come from a variety of sources. We performed searches in Pubmed, ScienceDirect, and Google Scholar using the terms "calcium channel blocker," "efficacy," "blood pressure response," "pharmacokinetic," and "polymorphism" OR "genetic" OR "genomic" to find pertinent articles. When prescription antihypertensive medications, particularly calcium channel blockers, it is important to take into account certain gene variants for example CYP3A5*3/*3, CYP3A4 *1G/*1G, MDR1 C3435T , RyR3 gene rs877087 because of their considerable effects.

The impact of gene polymorphism and hepatic insufficiency on voriconazole dose adjustment in invasive fungal infection individuals.

Voriconazole (VRZ) is a broad-spectrum antifungal medication widely used to treat invasive fungal infections (IFI). The administration dosage and blood concentration of VRZ are influenced by various factors, posing challenges for standardization and individualization of dose adjustments. On the one hand, VRZ is primarily metabolized by the liver, predominantly mediated by the cytochrome P450 (CYP) 2C19 enzyme. The genetic polymorphism of CYP2C19 significantly impacts the blood concentration of VRZ, particularly the trough concentration (Ctrough), thereby influencing the drug's efficacy and potentially causing adverse drug reactions (ADRs). Recent research has demonstrated that pharmacogenomics-based VRZ dose adjustments offer more accurate and individualized treatment strategies for individuals with hepatic insufficiency, with the possibility to enhance therapeutic outcomes and reduce ADRs. On the other hand, the security, pharmacokinetics, and dosing of VRZ in individuals with hepatic insufficiency remain unclear, making it challenging to attain optimal Ctrough in individuals with both hepatic insufficiency and IFI, resulting in suboptimal drug efficacy and severe ADRs. Therefore, when using VRZ to treat IFI, drug dosage adjustment based on individuals' genotypes and hepatic function is necessary. This review summarizes the research progress on the impact of genetic polymorphisms and hepatic insufficiency on VRZ dosage in IFI individuals, compares current international guidelines, elucidates the current application status of VRZ in individuals with hepatic insufficiency, and discusses the influence of CYP2C19, CYP3A4, CYP2C9, and ABCB1 genetic polymorphisms on VRZ dose adjustments and Ctrough at the pharmacogenomic level. Additionally, a comprehensive summary and analysis of existing studies' recommendations on VRZ dose adjustments based on CYP2C19 genetic polymorphisms and hepatic insufficiency are provided, offering a more comprehensive reference for dose selection and adjustments of VRZ in this patient population.

Adolescent Depressive Disorder and Gene Polymorphism

Biogenetics plays an important role in the pathogenesis of adolescent depression and the study of gene polymorphisms has updated the understanding of adolescent depression. However, under the influence of gene-environment interaction and adolescent developmental age factors, the impact of gene polymorphisms on adolescent depression is intricate. Studying and elucidating the relationship between depression-related gene polymorphisms and adolescent depression contributes to the study of the pathogenesis of depression and provides new clues for the prevention and treatment of depression in adolescents. This article reviews the related gene polymorphisms around adolescent depression.

Gene polymorphisms and risk of head and neck squamous cell carcinoma: a systematic review.

Exposure to the same environmental factors in different people have resulted in different susceptibility to head and neck squamous cell carcinoma (HNSCC), which suggests genetic variation may be a risk factor for the development of HNSCC. So, the aim was to review literatures on the association between gene polymorphisms and risk of HNSCCs. This systematic review included all articles on the impact of gene polymorphisms on risk and susceptibility to HNSCC published till September 2021 using PubMed, Web of science, SCOPUS, Google Scholar and Cochrane library databases. Of 1163 initial searched articles, 77 articles were eligible to include in this review. Studies were categorized based on gene functions. In each category, studied gene polymorphisms related to growth control genes, cell cycle control, apoptosis, DNA repair genes, carcinogen-metabolizing enzymes, alcohol-metabolizing genes, antioxidant gene, inflammatory cytokine, transcription factor, tumor immunity, folate metabolism, and tumor suppressor gene were discussed separately. Among the polymorphisms that are often significantly associated with HNSCC risk are: GSTM1 null, GSTT1 null, CYP2D6 *4, XRCC1 Arg194Trp and Arg399Gln, ERCC1 C8092A, XPD Lys751Gln, XRCC3 Thr241Met, P53 codon 72 and MTHFR C677T polymorphisms. Varied and contradictory results have been reported in different studies regarding the association of gene polymorphisms with HNSCC risk. To conclude about this association and to overcome these contradictions, it is necessary to use the results of existing meta-analyses or to perform new or updated meta-analyses.

GENE POLYMORPHISM AS A PREDICTOR DEVELOPMENT OF THE CHILDREN DISEASE

Neonates suffering from severe birth asphyxia may develop hypoxic ischemic encephalopathy and in some cases to permanent neurological damage. Around 20 – 50% of neonates with birth asphyxia who have hypoxic ischemic encephalopathy symptoms die in the neonatal period. Our study aims to clarify the role and impact of gene polymorphisms on the occurrence of hypoxic-ischemic encephalopathy. Hypoxic-ischaemic encephalopathy is a common cause of death and disability in newborns. It causes long-term or permanent damage, such as cerebral palsy, epilepsy, and certain forms of mental retardation. Autoregulation may be impaired during various neonatal disease and states including prematurity, hypoxic-ischemic encephalopathy, intraventricular haemorrhage, congenital cardiac disease, and infants requiring extracorporeal membrane oxygenation. As infants are especially sensitive to changes in cerebral blood flow, both hypoperfusion and hyperperfusion can cause significant neurologic injury. All of these conditions impair cerebral blood flow, leading to ischemia and hypoxia and trigger a cascade of deleterious biochemical events that seriously and permanently injure the brain. The nitric oxide produced by NOS3 plays a critical role in maintaining cerebral blood circulation and preventing neuronal injury. Mild exposure to ischemia activates enzyme NOS3 and produces small amounts of nitric oxide with subsequent relaxation of blood vessels and vasodilatation. Genetic factors could also affect the processes of autoregulation and destruction following hypoxic-ischemic injury. An underlying genetic predisposition that increases or decreases the degree of injury after a prenatal hypoxic ischemic event may affect the clinical course and prognosis. Except of therapeutic hypothermia, which currently is the only treatment available, a considerable number of newborns still have adverse outcomes. Therefore, there is a pressing need for novel better prognostic and diagnostic tools to improve outcome.

Impact of polymorphisms in genes orchestrating innate immune responses on replication kinetics of Torque teno virus after kidney transplantation.

Background: Torque teno virus (TTV) DNAemia has been proposed as a surrogate marker of immunosuppression after kidney transplantation (KT), under the assumption that the control of viral replication is mainly exerted by T-cell-mediated immunity. However, Tthe impact on post-transplant TTV kinetics of single genetic polymorphisms (SNPs) in genes orchestrating innate responses remains unknown. We aimed to characterize the potential association between 14 of these SNPs and TTV DNA levels in a single-center cohort of KT recipients. Methods: Plasma TTV DNAemia was quantified by real-time PCR in 221KT recipients before transplantation (baseline) and regularly through the first 12 post-transplant months. We performed genotyping of the following SNPs: CTLA4 (rs5742909, rs231775), TLR3 (rs3775291), TLR9 (rs5743836, rs352139), CD209 (rs735240, rs4804803), IFNL3 (rs12979860, rs8099917), TNF (rs1800629), IL10 (rs1878672, rs1800872), IL12B (rs3212227) and IL17A (rs2275913). Results: The presence of the minor G allele of CD209 (rs4804803) in the homozygous state was associated with undetectable TTV DNAemia at the pre-transplant assessment (adjusted odds ratio: 36.96; 95% confidence interval: 4.72-289.67; p-value = 0.001). After applying correction for multiple comparisons, no significant differences across SNP genotypes were observed for any of the variables of post-transplant TTV DNAemia analyzed (mean and peak values, areas under the curve during discrete periods, or absolute increments from baseline to day 15 and months 1, 3, 6 and 12 after transplantation). Conclusion: The minor G allele of CD209 (rs4804803) seems to exert a recessive protective effect against TTV infection in non-immunocompromised patients. However, no associations were observed between the SNPs analyzed and post-transplant kinetics of TTV DNAemia. These negative results would suggest that post-transplant TTV replication is mainly influenced by immunosuppressive therapy rather than by underlying genetic predisposition, reinforcing its clinical application as a biomarker of adaptive immunity.

Impacts of pregnane X receptor and cytochrome P450 oxidoreductase gene polymorphisms on trough concentrations of apixaban in patients with non-valvular atrial fibrillation.

We examined the impact of polymorphisms in genes encoding cytochrome P450 (CYP) 3A5 (gene code CYP3A5), P-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), cytochrome P450 oxidoreductase (POR), and pregnane X receptor (PXR; NR1I2) on the daily dose-adjusted steady-state trough concentrations (C0h/D) of apixaban. The analyses included 104 patients with non-valvular atrial fibrillation (NVAF) undergoing AF catheter ablation. The CYP3A5*3; ABCG2 421C > A; ABCB1 1236C > T, 2677G > A/T, 3435C > T, and 2482-2236G > A; NR1I2 11156A > C, 11193T > C, and 8055C > T; and POR*28 genotypes were determined. The combination of the noted NR1I2 genotypes determined the PXR*1B haplotype. Multiple linear regression analyses demonstrated that decreased creatinine clearance(Ccr) and the PXR*1B/*1B haplotype correlated with increased C0h/D of apixaban, while the presence of the POR*28 allele correlated with decreased C0h/D of apixaban (partial R2 = 0.168, 0.029, and 0.044, all P < 0.05). The mean (95% CI) of estimated marginal means of apixaban C0h/D calculated using Ccr as a covariate was the highest in POR*28 noncarriers with PXR*1B/*1B (23.5 [21.0-25.9] ng/mL/[mg/day]) and lowest in POR*28 carriers with other haplotypes (16.6 [15.5-17.7] ng/mL/[mg/day]). The PXR*1B haplotype and POR*28 genotype statuses, which involve genes that impact the expression of multiple drug-metabolizing enzymes and drug-transporters, may have modest effects on the C0h/D of apixaban, but these effects were found to be small.

Gene polymorphisms and post‐treatment toxicity and treatment response in head and neck squamous cell carcinoma: A scoping review

AbstractVariations in toxicity and treatment response are observed among patients with head and neck squamous cell carcinomas (HNSCCs) despite similar clinicopathologic characteristics that are attributed to gene polymorphisms. This study aimed to review the literatures about the impact of gene polymorphisms on post‐treatment toxicity and treatment response in HNSCCs. A systematic search of all original articles about impact of gene polymorphisms on toxicity and response rate in HNSCCs was done till September 2021 using Google Scholar and PubMed databases. Of 15 345 initial searched articles, 25 articles were finally found to be eligible for inclusion in this review. A total of 41 genes and 69 polymorphisms were examined in these studies. Twenty‐nine genes with 42 polymorphisms for treatment response and 21 genes with 33 polymorphisms were examined for post‐treatment toxicity. Because each of the Asp312Asn ERCC2, IIe105Val GSTP1, and Phe31Ile AurkA polymorphisms has been associated with significant results in two studies, these polymorphisms are more likely to be associated with a treatment response. In the same way, the R521K EGFR polymorphism is more likely to be associated with a post‐treatment toxicity. Because some polymorphisms such as R521K EGFR, *4 or *6 CYP2D6, and rs396991 FcγRIIIa have been associated with significant results in one study (without contradictory study), it is likely that they will be associated with a treatment response by further studies. Due to the paucity of studies, definitive conclusions are impossible, so further studies with meta‐analysis in the future are recommended.

Impact of gene polymorphism of glutathione S-transferase and ghrelin as a risk factor in Egyptian women with gestational diabetes mellitus

BackgroundGestational diabetes mellitus is the most common metabolic dysfunction that arises during pregnancy. GDM can lead to serious health complications for both the mother during pregnancy and after the delivery of the baby. Additionally, mother–offspring suffers from abnormalities in metabolism. The study aimed to investigate glutathione S‑transferase P1 and ghrelin genetic variants in pregnant women diagnosed with gestational diabetes using a tetra-primer amplification refractory mutation system.ResultsThis study demonstrated that the frequencies of genotypes in women with GDM were GSTP1-AG (87.1%) and GHRL-GG (100%). The study revealed no significant differences in the frequency of either genotype or allele of both GSTP1 and ghrelin between GDM and healthy pregnant women.ConclusionsThis study may be the first study designed to demonstrate that there is no association between the genotype and allele frequencies of GSTP1 (rs1695) and ghrelin (rs696217) in the development of gestational diabetes mellitus in Egyptian women.

Impact of gene polymorphism on Egyptian HCV patients under direct antiviral Drugs

Hepatitis C viral infection is with the highest prevalence rate in Egypt. Direct Acting Antivirals (DAAs) is now the standard of care for HCV infection treatment. Here we assess the predictive value of single-nucleotide polymorphisms (SNP) rs2596542 C/T in chromosome 6 located in MHC class I on the response to DAAs in chronic HCV infected Egyptian patients. This study was performed on 70 Egyptian patients positive for HCV; classified into two groups. Group I: (33 patients) were received combination therapy Sofosbuvir (Sovaldi) 400 mg/day plus Declatasvir 60 mg once daily, Group II: (37 patients) were received Ombitasvir 25 mg, Paritaprevir 150 mg and Ritonavir 100 mg/day plus Ribavirin 15 mg/kg/day for 12 weeks. HCV level by (RT-PCR), MICA single nucleotide polymorphism of rs2596542, ALT, AST, total bilirubin, serum albumin, fasting blood sugar, HbA1C %, CBC, serum creatinine, AFP were performed in all volunteer patients. Results showed that group II responded with 100% in CT- SNP genotype. However both CC and TT- SNP genotypes responded with 83.33% and 91.67% respectively. There was no observed significant association between SNP rs2596542 C/T and all clinical parameters except AFP that give positive significant correlation in the CC genotype.

Impact of gene polymorphisms in drug-metabolizing enzymes and transporters on trough concentrations of rivaroxaban in patients with atrial fibrillation.

Rivaroxaban is excreted from the body via multiple pathways involving glomerular filtration, drug-metabolizing enzymes and transporters. In this study, we aimed to examine the impact of single nucleotide polymorphisms in P-glycoprotein, breast cancer resistance protein, cytochrome P450 (CYP) 3A5 and CYP2J2 on the pharmacokinetics of rivaroxaban. Eighty-six patients with non-valvular atrial fibrillation (NVAF) undergoing AF catheter ablation were enrolled in this study. In these analyses, the dose-adjusted plasma trough concentration ratio (C0h /D) of rivaroxaban was used as the pharmacokinetic index. The median (quartile range) rivaroxaban C0h /D was 3.39 (2.08-5.21)ng/mL/mg (coefficient of variation: 80.5%). The C0h /D did not differ significantly among ABCB1 c.3435C>T, c.2677G>A/T, c.1236C>T, ABCG2 c.421C>A, CYP3A5*3 and CYP2J2*7 genotypes. Stepwise selection multiple linear regression analysis showed that the estimated glomerular filtration rate was the only independent factor influencing the C0h /D of rivaroxaban (R2 = 0.152, P< 0.001). There was a significant correlation between the C0h of rivaroxaban and prothrombin time (PT) (rho=0.357, P= 0.001). In patients with NVAF, pharmacokinetic genotype tests are unlikely to be useful for prediction of the C0h of rivaroxaban.

Pharmacogenetic score predicts overall survival, progression-free survival and platinum sensitivity in ovarian cancer.

Aim: To define the impact of polymorphisms in genes involved in platinum-taxane and estrogen activity in the outcome of platinum-based treated ovarian cancer patients (OCP). Patients &Methods: Two hundred and thirty OCP were analyzed for 124 germ-line polymorphisms to generate a prognosticscore for overall survival (OS), progression-free survival (PFS) and platinum-free interval (PFI). Results:ABCG2 rs3219191D>I, UGT1A rs10929302G>A and UGT1A rs2741045T>C polymorphisms were significantly associated with all three parameters (OS, PFS and PFI) and were used to generate a score. Patients in high-risk group had a poorer OS (hazard ratio [HR]: 1.8; 95% CI: 1.3-2.7; p=0.0019), PFS (HR: 2.0; 95% CI: 1.4-2.9; p<0.0001) and PFI (HR: 1.9; 95% CI: 1.4-2.8; p=0.0002) compared with those in low-risk group. Conclusion: The prognostic-score including polymorphisms involved in drug and estrogen pathways stratifies OCP according to OS, PFS and PFI.

Impact of Gene Polymorphisms in GAS5 on Urothelial Cell Carcinoma Development and Clinical Characteristics.

Urothelial cell carcinoma (UCC) is the commonest malignant tumor of the urinary tract and the second most common kidney cancer malignancy. Growth arrest-specific 5 (GAS5), a long noncoding RNA, is encoded by the GAS5 gene and plays a critical role in cellular growth arrest and apoptosis. In the current study, two single nucleotide polymorphisms (SNPs) in the GAS5 gene, rs145204276 and rs55829688, were selected to investigate correlations between these single SNPs and susceptibility to UCC. A total of 430 UCC cases and 860 ethnically matched healthy controls were included. SNP rs145204276 and SNP rs55829688 were determined using a TaqMan genotyping assay. Logistic regression models demonstrated that female patients with UCC carrying the rs145204276 GAS5 Ins/Del or Del/Del genotype had a 3.037-fold higher risk of larger tumor status (95% confidence interval 1.259–7.324) than did rs145204276 wild type (Ins/Ins) carriers (p = 0.011). The Cancer Genome Atlas validation cohort analysis demonstrated that the expression of GAS5 in female patients with bladder urothelial carcinoma (BLCA) with larger tumor size was much lower than that in patients with a smaller tumor size (p = 0.041). Kaplan-Meier curve analysis and the log–rank test revealed that female patients with BLCA and lower GAS5 expression had poorer overall survival than those with higher GAS5 expression. In conclusion, genetic variations in GAS5 rs145204276 may serve as a critical predictor of the clinical status of female patients with UCC.

Impact of gene polymorphisms on the systemic toxicity to paclitaxel/carboplatin chemotherapy for treatment of gynecologic cancers.

Gynecologic malignancies are often detected in advanced stages, requiring chemotherapy with taxane/platinum combinations, which may cause severe toxicities, such as neutropenia and peripheral neuropathy. Gene polymorphisms are suspected as possible causes for the interindividual variability on chemotherapy toxicities. To evaluate the role of ABCB1 1236C>T, 3435C>T; CYP2C8*3; CYP3A5*3C variants on paclitaxel/carboplatin toxicities. A cohort of 503 gynecologic cancer patients treated with paclitaxel/carboplatin at the Brazilian National Cancer Institute (INCA-Brazil) was recruited (2013-2017). Polymorphisms were genotyped by real-time PCR, and toxicities were evaluated by patients' interviews at each chemotherapy cycle and by data collection from electronic records. The association of clinical features and genotypes with severe toxicities was estimated using Pearson's Chi square tests and multiple regression analyses, with calculation of adjusted odds ratios (ORadjusted), and respective 95% confidence intervals (95% CI). CYP2C8*3 was significantly associated with increased risks of severe (grades 3-4) neutropenia (ORadjusted 2.11; 95% CI 1.24-3.6; dominant model) and severe thrombocytopenia (ORadjusted 4.93; 95% CI 1.69-14.35; recessive model), whereas ABCB1 variant genotypes (ORadjusted 2.13; 95% CI 1.32-3.42), in association with CYP2C8*3 wild type (GG) (ORadjusted 1.93; 95% CI 1.17-3.19), were predictive of severe fatigue. The present study suggests that CYP2C8*3 is a potential predictor of hematological toxicities related to paclitaxel/carboplatin treatment. Since hematological toxicities, especially neutropenia, may lead to dose delay or treatment interruption, such prognostic evaluation may contribute to clinical management of selected patients with paclitaxel-based chemotherapy.

The impact of gene polymorphism on warfarin therapy in children

The impact of gene polymorphism on warfarin therapy in children

Vitamin D pathway genetic variants are able to influence sofosbuvir and its main metabolite pharmacokinetics in HCV mono-infected patients

Vitamin D levels and genetic variants were associated with drug outcome/toxicity and concentrations. The plasma exposure of GS-331007, the main sofosbuvir metabolite, has been related to SVR. We evaluated the impact of polymorphisms in genes (CYP27B1, CYP24A1, VDBP and VDR) related to vitamin D pathway on sofosbuvir and GS-331007 plasma levels in HCV mono-infected patients at one month of treatment.Polymorphisms were investigated through real-time PCR; drug plasma quantification was performed through a UHPLC-MS/MS method.GS-331007 levels were associated with CYP24A1rs2248359 and VDRCdx2 variants in all the analyzed patients and linear regression analysis showed that sex, body mass index, HCV genotype, baseline estimated glomerular filtration rate, VDRCdx2AG/GG and CYP27B1-1260TT genotypes significantly predict concentrations. We performed sub-analyses considering the HCV genotype and the concomitant drug, identifying polymorphisms associated with GS-331007 concentrations.This is the first study focusing on vitamin D pathway gene variants and DAAs concentrations, but further studies are required.

GW28-e0117 Impact of Gene Polymorphisms, Platelet Reactivity, and the SYNTAX Score on 1-Year Clinical Outcomes in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

GW28-e0117 Impact of Gene Polymorphisms, Platelet Reactivity, and the SYNTAX Score on 1-Year Clinical Outcomes in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

The impact of gene polymorphisms in angiotensin receptor 1 and aldosterone synthase in peritoneal dialysis patients.

Longevity of peritoneal membrane is an important issue in patients treated with peritoneal dialysis (PD). In our study, we studied the impact of angiotensin receptor 1 (AGT R1) and aldosterone synthase (CYP11B2) gene polymorphism on peritoneal concentrations of interleukin-6 (PI-IL-6), vascular endothelial growth factor (PI-VEGF), plasminogen activator inhibitor-1 (PI-PAI-1), transforming growth factor-β (PI-TGF-β), and cancer antigen-125 (PI-CA-125) as known markers of peritoneal fibrosis. The single nucleotide polymorphism rs5186 (A1166C) in AGT R1 gene is located in 3' untranslated region (UTR) of the gene, while polymorphism rs1799998 (T -344 C) in CYP11B2 gene is located in the promoter region of the gene. We compared marker concentrations in patients with genotype DD vs. Dd and dd for AGT R1 and patients with genotype HH vs. Hh and hh for CYP11B2. The results show that polymorphism of CYP11B2 gene is associated with serum concentration of aldosterone. Patients with genotype HH had statistically significantly lower serum concentration of aldosterone (p=0.04). These patients also showed a trend to a lower rate of production of I-IL-6 (p=0.07), which correlated with lower concentrations of PAI-1 (p=0.002) and VEGF (p=0.005). AGT R1 gene polymorphism did not show any association with studied variables. Our findings suggest the possibility of genetic predisposition for development of peritoneal fibrosis that could be important for identification of patients with an "unfavorable" genotype, which could lead to customized prescription of appropriate therapy and personalized patient management. .

The Impact of Gene Polymorphisms on Anticoagulation Control With Warfarin.

Differences in warfarin maintenance dosages based on the presence of polymorphisms in VKORC1, CYP2C9, CYP4F2, and ORM1 can be determined through dosage adjustment according to routine guidelines. Little is known about whether routine therapy could provide consensus anticoagulation control for patients with different genotypes. This study was carried out to compare anticoagulant control in patients with different genotypes. Six hundred seventy patients using warfarin according to Chinese guidelines were enrolled. Warfarin dosages and monitored international normalized ratios (INRs) were recorded. Genotypes of VKORC1 rs9923231, CYP4F2 rs2108622, CYP2C9 rs1057910, and ORM1 rs17650 polymorphisms were determined. Warfarin dosages and INR were compared between genotypes. Patients with the AGCC*F*F*1*1 polymorphism took longer than patients with the AACC*F*F*1*1 polymorphism (20 vs 5 days, P < .001) to achieve the targeted INR range. The INR values of patients with AACC*F*F*1*3 were unstable and did not enter the stable state control phase until after 35 days. The peak INR of patients with the AACC*F*F*1*3 polymorphism was exceedingly high, with some values exceeding the control range limit of 3.0. Patients with the AACC*F*S*1*1 or AACT*F*F*1*1 polymorphisms exhibited similar INR values as the patients with the AACC*F*F*1*1 polymorphism. This study found that routine medication with warfarin provides significantly different levels of anticoagulant control between patients with wild-type genotypes and patients with heterozygous polymorphism genotypes of VKORC1 rs9923231 or CYP2C9 rs1057910. Patients with heterozygous polymorphism genotypes of VKORC1 or CYP2C9 require genotype-directed therapy with warfarin to increase efficacy and safety in anticoagulant treatment.

Prognostic impact of gene polymorphisms in patients with idiopathic sudden sensorineural hearing loss

Objective: To investigate whether genetic polymorphisms (single-nucleotide polymorphism [SNPs]) have a prognostic influence on hearing recovery after standardized corticosteroid therapy.Methods: A total of 192 gene samples from idiopathic sudden sensorineural hearing loss (SSNHL) patients registered in the Intractable Inner Ear Disease Gene Bank were enrolled and, as the candidate genes, 16 SNPs from 13 genes were selected for this study. Fischer’s exact test was used to compare allele frequencies in each SNP between the patients with good hearing recovery and patients with poor hearing recovery.Results: The SNPs of the GSR gene (rs2251780 and rs3779647) and NOS3 gene (rs1799983) were associated with treatment outcome (p < .05). Furthermore, there was a marginal correlation between the SNP of the NR3C1 gene (rs4912910) and treatment outcome (p = .05).Conclusions: The results of this study indicate that the analysis of genetic factors might make it possible to predict the treatment outcome, at least in part, in patients with idiopathic SSNHL.