Northern Chinese Patients Research Articles

Comparison of the Safety and Efficacy of Warfarin Versus Rivaroxaban in Northern Chinese Patients with Different CHA2DS2-VASc Scores: A Retrospective Cohort Study

Purpose: This study was aimed at evaluating the safety and efficacy of warfarin versus rivaroxaban in patients with atrial fibrillation (AF) and different CHA2DS2-VASc score subgroups in northern China. Methods: A retrospective cohort study was conducted to evaluate 387 patients with AF who received treatment at our institution between September 2018 and August 2019. The patients were divided into two groups receiving either warfarin (n=194) or rivaroxaban (n=193). Follow-up data were collected, including adherence, bleeding and ischemic stroke events. Results: The group receiving rivaroxaban showed better adherence than the group receiving warfarin. In the warfarin-treated group, bleeding incidents declined with increasing scores. In the warfarin-treated group, patients with scores of 2–3 had greater adherence and fewer stroke occurrences. The events of bleeding and stroke did not significantly differ in patients in the rivaroxaban-treated group with different scores. Conclusions: Compared with patients in the warfarin group with different CHA2DS2-VASc scores, those in the rivaroxaban group had greater compliance, and fewer bleeding and stroke events. Regardless of economic considerations, rivaroxaban is preferable for anticoagulative AF treatment in northern Chinese patients.

Growth Curves of Chinese Children with Androgen Insensitivity Syndrome: A Multicenter Registry Study.

Objective: To provide new information about androgen insensitivity syndrome (AIS), we studied growth patterns in Chinese children with AIS. Subjects: Data are from 118 untreated AIS patients who were admitted to eight pediatric endocrine centers from January 2010 to December 2019. Methods: In this retrospective cohort study, clinical data were collected from a multicenter database. We compared physical assessment data among AIS patients and standard growth charts for Chinese pediatric population. Results: 1. Children with AIS grew slightly less than the mean before 6 months of age, and then, height gradually increased before 12 years of age, from the median to +1 standard deviation (SD), according to the standard reference for Chinese pediatric population. After 12 years of age, height showed differently in profiles: The mean height in AIS patients gradually decreased from the mean to −1 SD, according to the standard for Chinese boys, and increased from the mean to +2 SD, according to the standard for Chinese girls. 2. The weights of children with AIS were greater than the mean standards of Chinese pediatric population from newborn to 11 years of age. From 12–16 years of age, the mean weight of children with AIS showed different profiles, from the mean to −1 SD, according to the standard for Chinese boys and from the mean to +1.5 SD, according to the standard for Chinese girls. 3. Weight standard deviation (WtSDS) and target height (THt) in northern Chinese AIS patients were significantly higher than those from the southern region (p = 0.035, 0.005, respectively). Age in northern Chinese AIS patients was significantly younger than those from the southern region (p = 0.034). No difference was found among birth weight (BW), birth length (BL), height standard deviation (HtSDS) and body mass index (BMI) in AIS patients from different regions (p > 0.05). 4. HtSDS and WtSDS in complete AIS (CAIS) patients were higher than those in partial AIS (PAIS) patients without significant difference (p > 0.05). Conclusions: Growth of children with AIS varied to different degrees. AIS patients seemed not to experience a puberty growth spurt. CAIS and PAIS patients show little difference in their growth. Regional differences have no effect on the height but influence the weight of AIS patients.

Standard-Dose Atorvastatin Treatment in Patients With Symptomatic Middle Cerebral Artery Atherosclerotic Stenosis: A Vessel Wall Magnetic Resonance Imaging Study.

Background and Purpose: Ischemic stroke can be caused by atherosclerotic lesions of the middle cerebral artery (MCA). Some studies have described the effects of statin treatment on carotid artery plaques, but little is known about the effects of statin treatment on MCA plaques. The purpose of this study was to validate the efficacy of standard-dose atorvastatin (20 mg/day) in patients with symptomatic MCA atherosclerotic stenosis (SMAS) in northern China.Materials and Methods: This study is a prospective, single-arm, single-center, 12-month follow-up observational study monitoring imaging, and clinical outcomes of standard-dose atorvastatin treatment among patients with SMAS. The primary outcomes were changes in vessel wall magnetic resonance imaging (VWMRI) and serum lipid profiles before and after (1, 3, 6, and 12 months) statin treatment.Results: A total of 46 patients were recruited for this study, and 24 patients completed the follow-up. During the follow-up period, serum non-high-density lipoprotein cholesterol concentrations gradually decreased in the patients. Fourteen patients (54.33%) had a reversal of MCA plaques and 10 patients (41.67%) had no significant progression of MCA plaques and remained stable at the follow-up endpoint. At the 12 months follow-up time-point, the treatment did not reverse vascular remodeling or change the shape and distribution of plaques. Altered serum low-density lipoprotein cholesterol (LDL-C) concentrations in patients were strongly associated with plaque reversal.Conclusion: Vessel wall magnetic resonance imaging could accurately characterize changes in MCA plaques after lipid-lowering therapy. Standard-dose atorvastatin treatment could stabilize and reverse plaques in northern Chinese patients with SMAS.

Patient-Generated Subjective Global Assessment (PG-SGA) predicts length of hospital stay in lung adenocarcinoma patients.

The prevalence of malnutrition is high among oncology patients in Northern China. Malnutrition is related to the longer hospital stay, and it can be used to predict the prognostic outcome of patients. This work focused on investigating the relationship of nutritional condition with the length of hospital stay (LOS) in Northern Chinese patients with lung adenocarcinoma (LUAD). The Patient-Generated Subjective Global Assessment (PG-SGA), Nutritional Risk Screening 2002 (NRS 2002) score, recent weight loss and BMI were assessed in a probabilistic sample of 389 LUAD patients without epidermal growth factor receptor (EGFR) mutations. This study collected the demographic and clinical features of patients in a prospective manner. Then, we examined the association of nutritional status with LOS among the population developing LUAD. According to the PG-SGA, 63 (16·3 %), 174 (44·7 %) and 78 (20·1 %) patients were at risk for undernutrition, moderate undernutrition and severe undernutrition, respectively. Nutritional risk was found in 141 (36·2 %) patients based on the NRS 2002. The average LOS for tumour patients in Northern China was 12·5 d. At admission, a risk of undernutrition or undernutrition according to the PG-SGA (P < 0·001), NRS 2002 (P < 0·001) and latest weight loss (P < 0·001) predicted the longer LOS. LOS was related to nutritional status and hospitalisation expenses (P < 0·001). LUAD patients who stayed in the ICU had a poorer nutritional status and a longer LOS (P < 0·001). In Northern Chinese patients with LUAD, a risk for undernutrition evaluated by the PG-SGA, the NRS 2002 and recent weight loss, but not BMI, could predict a longer LOS.

Clinical Features and Prognostic Factors in Northern Chinese Patients with Peripheral Granuloma Type of Ocular Toxocariasis: A Retrospective Cohort Study

ABSTRACT Purpose To summarize the clinical features and probable factors associated with recurrence within 6 months in northern Chinese ocular toxocariasis (OT) patients. Methods A retrospective cohort study (38 OT eyes) was conducted. Clinical features, aqueous inflammatory cytokines, complications, and parameters associated with recurrence after treatment were analyzed. Results The initial best-corrected visual acuity (BCVA) was related to the anterior inflammation grade at the onset (P = .028). The mean BCVA and anterior inflammation improved significantly (P < .05) after treatment. The OT eyes had higher aqueous humor cytokine levels (IL-6, IL-8, and IL-10) compared with the normal eyes (P < .001). More severe anterior inflammation grade or longer duration of uveitis were more likely to increase the probability of recurrence (P = .008 and P = .025), TA injection during/after vitreous surgery can reduce the probability of recurrence (P = .031). Conclusions The combination therapy of vitreoretinal surgery, steroids, and albendazole therapy may reduce inflammation and recurrence of OT effectively. Abbreviations: BCVA: best-corrected visual acuity; BFGF: basic fibroblast growth factor; CFT: central foveal thickness; CI: confidence interval; ELISA: Enzyme-linked immunosorbent assay; ERM: epiretinal membrane; IOP: intraocular pressure; IQR: interquartile range; IL: interleukin; LFM: laser flare meter; MH: macular hole; OCT: optical coherence tomography; OR: odds ratio; OT: ocular toxocariasis; RD: retinal detachment; TA: triamcinolone acetonide; TCLA: Toxocara canis larva crude antigen; TGF: transforming growth factor; VCAM: vascular cell adhesion molecule; VEGF: vascular endothelial growth factor

A functional polymorphism in the poly(ADP-ribose) polymerase-1 gene is associated with platinum-based chemotherapeutic response and prognosis in epithelial ovarian cancer patients

ObjectiveTo explore the effects of two functional genetic variants of poly(ADP-ribose) polymerase-1 (PARP-1) on the susceptibility to epithelial ovarian cancer (EOC), the platinum-based chemotherapeutic response, and the prognosis of northern Chinese patients. Study DesignThis case-control study included 710 EOC patients in the case group and 700 healthy women in the control group. Two polymorphisms (rs1136410 and rs8679) of PARP-1 were genotyped by polymerase chain reaction and ligase detection reaction. ResultsThe genotype frequencies of rs1136410 and rs8679 were not significantly different between the case and control groups. However, the CC genotype of rs1136410 was significantly associated with a favorable response to platinum drugs. Compared with the TT genotype, the CC genotype of rs1136410 was related to a reduced risk of platinum resistance (adjusted OR: 0.40; 95% CI = 0.24-0.67; P = 0.001). In addition, multivariable analysis containing clinical variables showed that patients who carried the rs1136410 CC genotype had a significantly improved progression-free survival compared with patients who carried the TT genotype (HR = 0.67, 95% CI = 0.47-0.97, P = 0.031). ConclusionThe rs1136410 polymorphism may serve as a potential marker for predicting the response to platinum agents and prognosis of EOC patients treated with surgery and platinum-based chemotherapy.

The correlation between plasma trimethylamine N-oxide level and heart failure classification in northern Chinese patients.

Trimethylamine N-oxide (TMAO) has been identified as a new biomarker of cardiovascular disease. Our aim was to evaluate the plasma levels of TMAO in patients with or without heart failure (HF), and to indicate the correlation between plasma TMAO level and HF classification in northern Chinese patients. A total of 112 control participants and 184 HF patients participated in this study. Plasma levels of TMAO and N-terminal probrain natriuretic peptide (NT-proBNP) in all participants were examined and analyzed. The plasma TMAO levels were remarkably higher in HF patients than that in control participants (7.0±0.6 vs. 1.5±0.1 μmol/L; P<0.01). In addition, the plasma TMAO levels of significantly increased from NYHA II to NYHA IV group (3.5±0.9, 6.0±0.8 and 8.1±1.0 μmol/L, respectively). The receiver operating characteristic analysis (ROC) showed that area under the curve (AUC) of TMAO was 0.881 (P<0.01). Furthermore, the AUC value for TMAO was 0.857 (95% CI: 0.674-1.000; P<0.01), 0.845 (95% CI: 0.778-0.911; P<0.01) and 0.914 (95% CI: 0.872-0.956; P<0.01) in NYHA II, NYHA III and NYHA IV groups, respectively. Univariate and multivariate logistic regression analysis indicated that TMAO was an independent risk factor for HF in patients. The level of TMAO was positively correlated with NT-proBNP. However, the diagnostic ability of TMAO was lower than that of NT-proBNP. TMAO was an independent predictor of HF, moreover, the TMAO levels were highly associated with HF classification in northern Chinese patients.

Association of FKBP5 polymorphisms with patient susceptibility to coronary artery disease comorbid with depression.

BackgroundCoronary artery disease (CAD) and depression cause great burden to society and frequently co-occur. The exact mechanisms of this comorbidity are unclear. FK506-binding protein 51 (FKBP51) is correlated with cardiovascular disease and depression. The aim of this study was to determine the role of the seven single nucleotide polymorphisms (SNPs) of FKBP5 that code FKBP51, namely, rs1360780 (C>T), rs2817032 (T>C), rs2817035 (G>A), rs9296158 (G>A), rs9470079 (G>A), rs4713902 (T>C), and rs3800373 (C>T) in a patient’s susceptibility to comorbid CAD and depression.MethodsWe enrolled 271 Northern Chinese Han patients with CAD, including 123 patients with depression and 147 patients without depression. We also included 113 healthy controls that match the patients’ sex and age. Genomic DNA from whole blood was extracted, and seven SNPs were assessed using MassArray method. Patient Health Questionnaire-9 was applied to access the depression.ResultsThe GA genotype for rs9470079 was associated with a significantly decreased risk of CAD (odds ratio = 0.506, 95% confidence interval = 0.316–0.810, P = 0.005) when the GG genotype was used as reference. A statistically significant difference was observed among females but not among males in the rs9470079 genotype and allele frequency. Patients with CAD were further divided into CAD+D and CAD-D groups according to the presence of comorbid depression and were compared with the controls. Significant differences were found regarding the genotype and allele frequency of rs2817035 and rs9470079 in CAD+H groups compared with the control subjects in all groups and the female groups (P < 0.05).ConclusionsThe current study found a remarkable association between FKBP5 gene variations and the risk of comorbid CAD and depression in a north Chinese population. rs9470079 may be a potential gene locus for the incidence of comorbid CAD and depression.

Impact of genetic and clinical factors on warfarin therapy in patients early after heart valve replacement surgery.

Factors influencing responsiveness to warfarin at treatment onset time were not well identified in Chinese patients undergoing heart valve replacement. We sought to select the most relevant factors that associated with patient response to warfarin early after heart valve surgery. In this observational study, 289 patients starting warfarin therapy early after heart valve replacement surgery were enrolled. CYP2C9 *1, *2, *3, and *5; VKORC1-1639 G>A, CYP4F2 V433M, and GGCX rs11676382 genotypes; clinical characteristics, response to therapy, and bleeding and thrombosis events were collected. The primary outcomes were the time to the first INR equal to or more than lower limit of therapeutic range and the warfarin dose requirements. Stepwise multiple linear regression was performed to develop a dosing algorithm to predict the warfarin dose requirements. The results of univariate analysis showed lone VKORC1-1639 G>A, CYP2C9 *1/*3, cefazolin, cefoperazone-sulbactam, increased BMI, Δhemoglobin, and white blood cell count could significantly affect patient responsiveness to warfarin in the initial period of anticoagulation. Multivariate analysis resulted in an equation: Accumulated warfarin doses (mg) = 17.068 VKORC1-1639 G>A - 4.261 hypertension + 0.593 BMI - 0.115 age - 4.852 CYP2C9 *1/*3 - 2.617 cefazolin - 4.902 cefoperazone-sulbactam - 4.537, which could explain 40.2% of the variability in warfarin dose needed to reach the first INR equal to or more than lower limit of therapeutic range. Both genetic and clinical factors contributed to anticoagulation effect of warfarin in the initial period of treatment. Our findings could provide a basis for the personalized management of warfarin use in the early stage of anticoagulation in northern Chinese patients.

Different EPHX1 methylation levels in promoter area between carbamazepine-resistant epilepsy group and carbamazepine-sensitive epilepsy group in Chinese population

BackgroundEpigenetics underlying refractory epilepsy is poorly understood. DNA methylation may affect gene expression in epilepsy patients without affecting DNA sequences. Herein, we investigated the association between Carbamazepine-resistant (CBZ-resistant) epilepsy and EPHX1 methylation in a northern Han Chinese population, and conducted an analysis of clinical risk factors for CBZ-resistant epilepsy.MethodsSeventy-five northern Han Chinese patients participated in this research. 25 cases were CBZ-resistant epilepsy, 25 cases were CBZ-sensitive epilepsy and the remaining 25 cases were controls. Using a CpG searcher was to make a prediction of CpG islands; bisulfite sequencing PCR (BSP) was applied to test the methylation of EPHX1. We then did statistical analysis between clinical parameters and EPHX1 methylation.ResultsThere was no difference between CBZ-resistant patients, CBZ-sensitive patients and healthy controls in matched age and gender. However, a significant difference of methylation levels located in NC_000001.11 (225,806,929.....225807108) of the EPHX1 promoter was found in CBZ-resistant patients, which was much higher than CBZ-sensitive and controls. Additionally, there was a significant positive correlation between seizure frequency, disease course and EPHX1 methylation in CBZ-resistant group.ConclusionMethylation levels in EPHX1 promoter associated with CBZ-resistant epilepsy significantly. EPHX1 methylation may be the potential marker for CBZ resistance prior to the CBZ therapy and potential target for treatments.

Genetic polymorphisms of PAX1 are functionally associated with different PUMC types of adolescent idiopathic scoliosis in a northern Chinese Han population

IntroductionPAX1 has been identified to be associated with adolescent idiopathic scoliosis (AIS). However, data are unavailable for northern Chinese populations, and it is important to determine the exact clinical phenotypes of the associated genetic polymorphisms. MethodsFive PAX1 single nucleotide polymorphism (SNP) loci were genotyped in 480 northern Chinese Han AIS patients and 841 controls. A stratified genotype-phenotype correlation analysis was conducted based on positive SNP loci and the Peking Union Medical College (PUMC) classification system. Luciferase assays were performed to determine the regulation of PAX1 transcriptional activity. ResultsThe A allele of rs17861031 and the G allele of rs6137473 were significantly associated with AIS [p = 0.05 and 3.12 × 10−3, odds ratio (OR) = 0.78 and 1.30, respectively]. Moreover, rs17861031 may regulate the PAX1 gene. The A allele of rs17861031 was identified as a risk allele for PUMC type I AIS (p = 0.03), and the G allele of rs6137473 was identified as a risk allele for PUMC type II AIS (p = 1.90 × 10−3). ConclusionsBoth rs17861031 and rs6137473 were significantly associated with AIS and different PUMC classifications of AIS in a northern Chinese Han population.

Relationship between body mass index and outcomes for patients with oral squamous cell carcinoma.

The purpose of our study was to investigate body mass index (BMI) as a prognostic factor and to examine the relationship between pretreatment BMI and oral squamous cell carcinoma (OSCC) outcomes in northern Chinese patients. This retrospective study enrolled 633 patients with OSCC who underwent surgery between 2004 and 2014. Most baseline characteristics (gender, sites, smoking history, comorbidity, hypertension, T stage, clinical features, perineural invasion, flap reconstruction) were differentiated by BMI groups. Overall, the Kaplan-Meier curves indicated no significant relationship between BMI and disease-free survival (DFS) or disease-specific survival (DSS). Interestingly, obese patients exhibited higher risks of recurrence and death than normal-weight patients (DFS: HR: 1.86, 95% CI: 1.16-2.96; DSS: HR: 2.04, 95% CI: 1.08-3.86). However, postoperative complications occurred more frequently in underweight patients than in normal-weight patients. Obesity may contribute to a higher recurrence rate and a worse prognosis in OSCC patients than in normal-weight patients in northern China. However, underweight patients have a higher risk of postoperative complications.

Bifid variations of the mandibular canal: cone beam computed tomography evaluation of 1000 Northern Chinese patients

The aim of this study was to evaluate and quantify variations of bifid mandibular canals (BMCs) in a population of Northern China by using cone beam computed tomography (CBCT). CBCT images of 1000 consecutive patients were analyzed by using the NewTom proprietary software. BMCs were identified and classified on the basis of the Naitoh classification. Linear and angular measurements of BMCs were performed. Statistical analyses were conducted by using χ2 and Wilcoxon tests. BMCs were observed in 13.2% of 1000 patients and 8.4% of 2000 sides. The prevalence of BMCs was significantly lower in patients in the first 2 decades and in cases with a class II molar relationship. The retromolar canal (68.4%) was the most common type of BMC observed. No buccolingual canals were identified; however, 2 special canals were detected. A classification system of 3 subtypes of retromolar canals was suggested. On average, the beginning site of the branches from the opening of the main canal was at a distance of 8.1mm. The mean diameter and length of BMCs were 2.1mm and 12.6mm, respectively. This study underlined the prevalence and characteristics of BMCs in a population of Northern China. Preoperative identification of BMCs with CBCT may help prevent postoperative complications.

The Polymorphism in ADORA3 Decreases Transcriptional Activity and Influences the Chronic Heart Failure Risk in the Chinese.

Aim To investigate the genetic contribution of adenosine A3 receptor (ADORA3) gene polymorphisms in the pathogenesis of chronic heart failure (CHF). Methods Firstly, a case-control study was performed to investigate the association of ADORA3 polymorphisms with CHF risk. Three hundred northern Chinese Han CHF patients and 400 ethnicity-matched healthy controls were included. Four polymorphisms were genotyped. This case-control study was also replicated in 304 CHF patients and 402 controls from southern China. Finally, the functional variability of positive polymorphism was analyzed using luciferase reporter assay and real-time PCR. Results Overall, the rs1544223 was significantly associated with CHF risk under the dominant model (P = 0.046, OR = 1.662, 95% CI = 1.009–2.738). But it did not affect disease severity. These results were also consistent in replicated population. In addition, the transcriptional activity for promoter with the A allele was lower than that with the G allele (n = 3, 4.501 ± 0.308 versus 0.571 ± 0.114, P < 0.01) and ADORA3 mRNA levels were significantly higher in GG homozygotes than subjects carrying GA (n = 6, 0.058 ± 0.01 versus 0.143 ± 0.068, P = 0.004) or AA genotypes (n = 6, 0.065 ± 0.01 versus 0.143 ± 0.068, P = 0.008). Conclusions Should the findings be validated by further studies with larger patient samples and in different ethnicities, they may provide novel insight into the pathogenesis of CHF.

Association of IL17RC and COL6A1 genetic polymorphisms with susceptibility to ossification of the thoracic posterior longitudinal ligament in Chinese patients

BackgroundIn our previous whole-genome sequencing study of 30 unrelated northern Chinese Han patients, we identified six single nucleotide polymorphisms (SNPs) in the interleukin 17 receptor C (IL17RC) and collagen type VI α1 chain (COL6A1) genes that were potentially associated with thoracic ossification of the posterior longitudinal ligament (T-OPLL). To determine whether these six SNPs are associated with susceptibility to T-OPLL in the northern Chinese Han population, we performed a case-control association study to confirm specific susceptible loci in the expanded samples.MethodsThe six SNPs in the IL17RC and COL6A1 genes were analyzed in 200 northern Chinese individuals (100 patients and 100 control subjects) using the Sequenom system.ResultsThe genotype distributions and allele frequencies of each SNP in the control and patient groups were compared. rs201153092, rs13051496, rs199772854, rs76999397, and rs189013166 showed potential pathogenic loci for T-OPLL in the northern Chinese Han population, whereas rs151158105 did not. At the genotype level, the differences in the genotype frequencies of rs201153092, rs13051496, rs199772854, rs76999397, and rs189013166 between T-OPLL cases and controls reached statistical significance.ConclusionsTo the best of our knowledge, this is the first association study of susceptibility genes in Han Chinese patients with T-OPLL. The results revealed five SNPs in the IL17RC and COL6A1 genes that represented potentially pathogenic mutations in patients with T-OPLL.

Genetic polymorphisms of GPR126 are functionally associated with PUMC classifications of adolescent idiopathic scoliosis in a Northern Han population.

GPR126 has been identified to be associated with AIS (Adolescent Idiopathic Scoliosis) in different populations, but data on the northern Chinese population are unavailable. Additionally, it is important to know the exact clinical phenotypes associated with specific genetic polymorphisms. Fourteen SNP (single nucleotide polymorphism) loci in GPR126 were genotyped in 480 northern Chinese Han AIS patients and 841 controls. These patients were classified into three types based on the PUMC classification system. Luciferase assays were used to investigate their regulation of GPR126 transcription activity. Combined and stratified genotype–phenotype association analyses were conducted. The alleles rs225694, rs7774095 and rs2294773 were significantly associated with AIS (P = 0.021, 0.048 and 0.023, respectively). rs225694 and rs7774095 potentially have regulatory functions for the GRP126 gene. Correlation analysis revealed that allele A of rs225694 was a risk allele only for PUMC type II AIS (P = 0.036) and allele G of rs2294773 was a risk allele only for PUMC type I AIS (P = 0.018). In summary, rs225694, rs7774095 and rs2294773 are significantly associated with disease in northern Chinese Han AIS patients. The SNPs rs225694 and rs2294773 are associated with different AIS PUMC classifications.

Identification of susceptibility loci for thoracic ossification of the posterior longitudinal ligament by whole-genome sequencing.

Ossification of the posterior longitudinal ligament (OPLL) is a myelopathy commonly observed in the cervical spine. By contrast, thoracic OPLL (T‑OPLL) is rare but more severe. Previous studies have identified several polymorphisms in osteogenic genes that are associated with the occurrence and development of cervical OPLL. However, few genetic studies have evaluated T‑OPLL. The present study aimed to identify the genetic factors for OPLL by performing whole‑genome sequencing (WGS) in 30 unrelated northern Chinese Han patients with T‑OPLL. Using bioinformatics analyses and damaging‑variant prediction algorithms, two deleterious variants [c.1534G>A(p.Gly512Ser)/collagen, type VI,α1 (COL6A1)] and [c.2275C>A(p.Leu759Ile)/inteleukin-17 receptorC (IL17RC)] were identified in seven unrelated patients. These two mutations resulted in markedly increased gene expression levels in peripheral blood samples. To the best of our knowledge, this is the first report to describe the use of WGS analysis of T‑OPLL in the northern Chinese Han population. The results revealed two novel potentially pathogenic mutations in patients with T‑OPLL.

Abstract LB-277: Four noval activating and resistance mutations of EGFR drug response targets were discovered in northern Chinese patients

Abstract Background and Objective: Lung cancer is the most rapidly developed cancer in terms ofmorbidity and fatality rate. The presence of EGFR mutations is a useful tool to determine NSCLC patients' prognosis. But there are differences in Eastern Asian and European and American. The aim of this study is to discoveryand validate the new EGFR drug targets in Northern Chinese patients with non-small cell lung cancer (NSCLC) via bioinformatics analysis, molecular biology experiments and clinical outcomes, and raise new possibilities for designing personalized treatments for patients carrying specific mutations. Methods: In this study, a new computational method and drug model was firstly established by referring to the HotSpot3D[1], which was applied to process mutagenesis data and identify new drug targets. We subsequently applied the computationaltool to more than 500 tumors of NSCLC patients in North China.The captured target DNAs were analyzed by next-generation sequencing using a nine gene lung cancer panel to find somatic variations. We then validated our predictions in cell-line-based experimental combining the results of the clinical follow-up. Results: We used a new computational tool to analyze more than 500 tumors data of NSCLC patients in North China, discovering several rarely reported druggable mutations, including EGFR mutations (p.Val742Ile, p.Ile789Met, p.Asn842His) with erlotinib, gefitinib, lapatinib and EGFR mutations (p.Ser811Cys) with afatinib. Furthermore, we performed an experiment examining the sensitivity of the EGFR proteins with these variants to the target drugs mentioned above. We found that EGFR with the p.Ile789Metvariant was sensitive to gefitinib, consistent with a previous report [1]. In parallel, of the 500NSCLC patients, 200 were treated with the above targetdrugs, and clinical outcomes of treated patients were collected. The results were consistent with the cell-line-based experiments. Verification of other EGFR variants is still in progress. Conclusion: In this study, severalnew EGFR druggable mutations were for the first time found and validated in NorthernChinese patients with non-small cell lung cancer (NSCLC). Our results will provide better treatment options for patients carryingthese specific mutations. [1] Niu B, Scott A D, Sengupta S, et al. Protein-structure-guided discovery of functional mutations across 19 cancer types[J]. Nature Genetics, 2016, 48(8). Citation Format: Geng Tian. Four noval activating and resistance mutations of EGFR drug response targets were discovered in northern Chinese patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-277. doi:10.1158/1538-7445.AM2017-LB-277

Clinical and Molecular Characterization of Infantile-Onset Pompe Disease in Mainland Chinese Patients: Identification of Two Common Mutations.

We sought to understand the clinical course and molecular defects of infantile-onset Pompe disease (IOPD) among mainland Chinese patients. Twenty-five Chinese patients with IOPD were enrolled and clinical data were retrospectively reviewed. The entire coding region of the GAA gene was amplified by polymerase chain reaction and analyzed by direct sequencing. The median age at symptom onset was 3.4 months (range: 1.0-7.1 months) and 4.9 months (range: 2.7-8.3 months) at diagnosis. Only one patient received enzyme replacement therapy (ERT) and this child survived beyond the age of 2 years. Of the 24 patients not receiving ERT, all, but one patient, died at a median age of 8.3 months (range: 4.0-12.2 months). Thirteen novel and two common GAA mutations were identified in this study. The allelic frequency of c.2662G > T (p.Glu888X) was 23.1% in northern Chinese patients and 4.2% in southern Chinese patients, whereas the allelic frequency of c.1935C > A (p.Asp645Glu) was 20.8% in southern and 3.8% in northern Chinese patients. We identified the most common mutations in southern and northern Chinese patients with IOPD.

Clinical and genetic factors associated with warfarin maintenance dose in northern Chinese patients with mechanical heart valve replacement

The effects of genetic variants on warfarin dosing vary among different ethnic groups, especially in the Chinese population. The objective of this study was to recruit patients through a rigorous experimental design and to perform a comprehensive screen to identify gene polymorphisms that may influence warfarin dosing in northern Han Chinese patients with mechanical heart valve replacement. Consenting patients (n = 183) with a stable warfarin dose were included in this study. Ninety-six single nucleotide polymorphisms (SNPs) in 30 genes involved in warfarin pharmacological pathways were genotyped using the Illumina SNP GoldenGate Assay, and their associations with warfarin dosing were assessed using univariate regression analysis with post hoc comparison using least significant difference analysis. Multiple linear regression was performed by incorporating patients' clinical and genetic data to create a new algorithm for warfarin dosing. From the 96 SNPs analyzed, VKORC1 rs9923231, CYP1A2 rs2069514, CYP3A4 rs28371759, and APOE rs7412 were associated with higher average warfarin maintenance doses, whereas CYP2C9 rs1057910, EPHX1 rs2260863, and CYP4F2 rs2189784 were associated with lower warfarin doses (P < 0.05). Multiple linear regression analysis could estimate 44.4% of warfarin dose variability consisting of, in decreasing order, VKORC1 rs9923231 (14.2%), CYP2C9*3 (9.6%), body surface area (6.7%), CYP1A2 rs2069514 (3.7%), age (2.7%), CYP3A4 rs28371759 (2.5%), CYP4F2 rs2108622 (1.9%), APOE rs7412 (1.7%), and VKORC1 rs2884737 (1.4%). In the dosing algorithm we developed, we confirmed the strongest effects of VKORC1, CYP2C9 on warfarin dosing. In the limited sample set, we also found that novel genetic predictors (CYP1A2, CYP3A4, APOE, EPHX1, CYP4F2, and VKORC1 rs2884737) may be associated with warfarin dosing. Further validation is needed to assess our results in larger independent northern Chinese samples.