Polymerase Chain Reaction-ligase Detection Research Articles

Single nucleotide polymorphisms of GEMIN3 modify the risk of primary Sjögren's syndrome in female patients

BackgroundMicroRNA (miRNA)-processing machinery may modify the risk of primary Sjögren's syndrome (pSS) by altering miRNA expression profiles. Inflammatory cytokines and reactive oxygen species (ROS) are also involved in pSS; however, the role of altered miRNAs expression in its pathogenesis is still unclear. We aimed to evaluate the relationship between single-nucleotide polymorphisms (SNPs) in miRNA processing machinery genes, including XPO5 (rs11077), RAN (rs14035), Dicer (rs3742330), TNRC6B (rs9623117), GEMIN3 (rs197412), and GEMIN4 (rs2740348), and the risk of pSS in female patients. The potential associations of cytokines and ROS with pSS-susceptible SNPs were also evaluated. Materials and MethodsThe SNPs confirmed by polymerase chain reaction ligase detection reaction were genotyped in 74 female patients with pSS and 77 controls. The relationship was analyzed by Student's t-test, Wilcoxon rank-sum test, chi-square test, Pearson's correlation test, and binary logistic regression analysis. ResultsFor rs197412 of the GEMIN3 gene, the genotype TT carrier was associated with a 2.172-fold increased risk for pSS when compared with that of CT+CC carrier (odds ratio: 2.172, 95% CI, 1.133–4.166, p=0.019). Simultaneously, the pSS-susceptible TT carriers were associated with increased interferon-γ (IFN-γ) (P < 0.001) and tumor necrosis factor-α (TNF-α) (P = 0.003) levels when compared with that of CT+CC genotype carriers in female patients with pSS. The subsequent analysis also showed a weak positive correlation between IFN-γ and TNF-α levels (r=0.271, P = 0.019). ConclusionThe predictors of GEMIN3 SNPs might modify pSS development in females by mediating the expression of miRNAs and therefore regulate the levels of IFN-γ and TNF-α.

Genetic variations in ACE2 gene associated with metabolic syndrome in southern China: a case–control study

Metabolic syndrome (MetS) is closely related to cardiovascular and cerebrovascular diseases, and genetic predisposition is one of the main triggers for its development. To identify the susceptibility genes for MetS, we investigated the relationship between angiotensin-converting enzyme 2 (ACE2) single nucleotide polymorphisms (SNPs) and MetS in southern China. In total, 339 MetS patients and 398 non-MetS hospitalized patients were recruited. Four ACE2 polymorphisms (rs2074192, rs2106809, rs879922, and rs4646155) were genotyped using the polymerase chain reaction-ligase detection method and tested for their potential association with MetS and its related components. ACE2 rs2074192 and rs2106809 minor alleles conferred 2.485-fold and 3.313-fold greater risks of MetS in women. ACE2 rs2074192 and rs2106809 variants were risk factors for obesity, diabetes, and low–high-density lipoprotein cholesterolemia. However, in men, the ACE2 rs2074192 minor allele was associated with an approximately 0.525-fold reduction in MetS prevalence. Further comparing the components of MetS, ACE2 rs2074192 and rs2106809 variants reduced the risk of obesity and high triglyceride levels. In conclusion, ACE2 rs2074192 and rs2106809 SNPs were independently associated with MetS in a southern Chinese population and showed gender heterogeneity, which can be partially explained by obesity. Thus, these SNPs may be utilized as predictive biomarkers and molecular targets for MetS. A limitation of this study is that environmental and lifestyle differences, as well as genetic heterogeneity among different populations, were not considered in the analysis.

Association Between Polymorphism in Diabetes Susceptibility Gene Insulin-Like Growth Factor 2mRNA-Binding Protein 2 and Risk of Diffuse Large B-Cell Lymphoma.

Numerous studies have shown that polymorphisms in the diabetes susceptibility gene, insulin-like growth factor 2mRNA-binding protein 2 (IGF2BP2), are associated with the occurrence and development of various malignant tumors; however, their correlation with the onset of diffuse large B-cell lymphoma (DLBCL) is still unknown. Therefore, this study aimed to explore whether IGF2BP2 polymorphisms increase the risk of developing DLBCL. This study included 295 DLBCL patients and 331 healthy individuals. Peripheral blood was collected, and polymerase chain reaction-ligase detection reaction (PCR-LDR) was used to detect IGF2BP2 gene polymorphisms. Logistic regression was used to assess the association between IGF2BP2 polymorphism and the risk of DLBCL, adjusted for age, sex, and body mass index (BMI). P < .05 indicated statistical significance. The rs4402960 polymorphism in the IGF2BP2 gene was associated with the occurrence and development of DLBCL. After adjusting for age, sex, and BMI, GT (odd ratio [OR] = 1.54; 95% confidence interval [CI] = 1.08-2.19; P = .016), TT (OR = 2.00; 95% CI = 1.09-3.68; P = .026), and T genotype carrying (GT + TT) (OR = 1.62; 95% CI = 1.17-2.25; P = .004) significantly increased the risk of DLBCL. This study also found that the polymorphism rs1470579 was related to the development of DLBCL. After adjusting for age, sex, and BMI, AC (OR = 1.55; 95% CI = 1.11-2.17; P = .010), CC (OR = 2.18; 95% CI = 1.17-4.06; P = .014), and C genotype carrying (AC + CC) (OR = 1.64; 95% CI = 1.19-2.26; P = .002) significantly increased the risk of DLBCL. Our study found that polymorphism in the IGF2BP2 gene was associated with an increased risk of developing DLBCL.

Association of Gene Polymorphisms in CXC Chemokine Receptor 5 with Rheumatoid Arthritis Susceptibility.

Rheumatoid arthritis (RA) is caused by complicated interactions between genes and the environment. CXC chemokine receptor 5 (CXCR5) is required for B and T follicular helper cell migration and humoral immunity generation. Therefore, this study aimed to assess whether polymorphisms of the CXCR5 gene are implicated in RA development and progression. This case-control study enrolled 285 RA patients and 291 healthy controls. The polymerase chain reaction-ligase detection reaction method was used to genotype rs630923, rs497916, rs3922, and rs676925 in the CXCR5 gene. Epidemiological, clinical, and laboratory data were collected retrospectively. The rs630923 A allele was associated with a higher risk of RA (AOR [adjusted odds ratio]=2.00, 95% confidence interval [CI] =1.14-3.53). However, in the RA group, the frequency of the rs497916 T allele was lower (AOR=0.69, 95% CI=0.51-0.93). Regarding rs3922, AG+GG genotype carriers were at a significantly lower risk for RA than AA genotype carriers (AOR=0.70, 95% CI=0.49-0.99). In the RA group, we found that the different genotypes were significantly associated with specific laboratory values, including rheumatoid factor, total bilirubin, total cholesterol, low-density lipoprotein cholesterol, and alkaline phosphatase. This is the first report indicating that CXCR5 polymorphisms were associated with RA susceptibility. These findings lead to a rising possibility of identifying RA-susceptible individuals based on genetic markers.

A functional polymorphism of microRNA-143 is associated with the risk of type 2 diabetes mellitus in the northern Chinese Han population.

ObjectiveTo explore the association between two polymorphisms of microRNA-143 (miR-143) and the risk of type 2 diabetes mellitus (T2DM) in the northern Chinese Han population.Study DesignThis case–control study involved 326 patients with T2DM and 342 healthy controls. Two genetic variants (rs4705342 and rs353292) of miR-143 were genotyped by the polymerase chain reaction/ligase detection reaction (PCR-LDR) method. The levels of miR-143 in the serum from 52 T2DM patients and 55 healthy subjects were investigated by quantitative real-time PCR (qRT–PCR).ResultsThe CC genotype frequency of rs4705342 was significantly higher in the T2DM patients than in the healthy controls (P = 0.012). After adjusting for sex, age, and body mass index, the rs4705342 CC genotype was also related to a significantly increased risk of T2DM compared with the TT genotype (adjusted OR: 1.87; 95% CI = 1.09-3.19; P = 0.022). Stratified analyses demonstrated that T2DM patients with the rs4705342 CC genotype had significantly higher levels of low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), and glycated haemoglobin (HbA1C) than those carrying the rs4705342 TT genotype. The qRT–PCR results showed that the expression levels of miR-143 were significantly higher in the serum of cases than in the serum of controls (P < 0.001). Furthermore, the levels of miR-143 were significantly higher in the serum of T2DM patients carrying the rs4705342 CC genotype than in those carrying the TC and TT genotypes of rs4705342 (P = 0.005 and 0.003, respectively).ConclusionThe CC genotype of rs4705342 might be a risk factor for developing T2DM by increasing the expression of miRNA-143 in the northern Chinese Han population.

Association of rs2072446 in the NGFR gene with the risk of Alzheimer's disease and amyloid-β deposition in the brain.

Alzheimer's disease (AD) is the most common form of dementia with a complex genetic background. The cause of sporadic AD (sAD) remains largely unknown. Increasing evidence shows that genetic variations play a crucial role in sAD. P75 neurotrophin receptor (p75NTR, encoded by NGFR) plays a critical role in the pathogenesis of AD. Yet, the relationship between NGFR gene polymorphisms and AD was less studied. This study aims to analyze the relationship of NGFR gene polymorphism with the risk of AD in the Chinese Han population and amyloid-β deposition in the ADNI cohort. This case-control association study was conducted in a Chinese Han cohort consisting of 366 sporadic AD (sAD) patients and 390 age- and sex-matched controls. Twelve tag-SNPs were selected and genotyped with a multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) method. The associations between tag-SNPs and the risk of AD were analyzed by logistic regression. Moreover, another cohort from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database was included to examine the association of one tag-SNP (rs2072446) with indicators of amyloid deposition. Kaplan-Meier survival analysis and Cox proportional hazards models were used to test the predictive abilities of rs2072446 genotypes for AD progression. The mediation effects of Aβ deposition on this association were subsequently tested by mediation analyses. After multiple testing corrections, one tag-SNP, rs2072446, was associated with an increased risk of sAD (additive model, OR=1.79, Padjustment =0.0144). Analyses of the ADNI cohort showed that the minor allele (T) of rs2072446 was significantly associated with the heavier Aβ burden, which further contributed to an increased risk of AD progression in APOE ε4 non-carrier. Our study found that rs2072446 in NGFR is associated with both the risk of sAD in the Chinese Han population and the amyloid burden in the ADNI cohort, which reveals the role of p75NTR in AD from a genetic perspective.

Genetic Variation of PD-L1 Gene Affects its Expression and Is Related to Clinical Outcome in Epithelial Ovarian Cancer.

ObjectiveThis study aims to investigate the effect of polymorphisms of programmed cell death-ligand 1 (PD-L1) on the risk and patient’s outcomes of epithelial ovarian cancer (EOC).MethodsTotally, 568 patients and 532 healthy women were included. Three polymorphisms in the PD-L1 gene, rs2297136, rs4143815 and rs4742098, were genotyped by the polymerase chain reaction/ligase detection reaction (PCR-LDR). Survival analysis was performed in 234 patients (received primary debulking surgery followed by platinum-based chemotherapy).ResultsPatients with the rs2297136 AG + GG genotypes had shorter progression-free survival (PFS) (hazard ratio (HR)=1.44, 95% CI=1.03-2.01) and overall survival (OS) (HR=1.55, 95% CI=1.06-2.27) than those with the AA genotype. Moreover, the mRNA and protein expression levels of PD-L1 in EOC tissues with the rs2297136 AG + GG genotypes were remarkably higher than those with the AA genotype (P=0.032 and P=0.047, respectively). Survival analysis showed that high expression of PD-L1 mRNA was remarkably associated with worse 10-year PFS (HR=1.55, 95% CI=1.28-1.88) and OS (HR=1.51, 95% CI=1.00-2.28) in EOC patients.ConclusionsThe rs2297136 may not only effectively influence the expression of PD-L1, but also is significantly associated with EOC patients’ outcomes.

Association Between ABCA1 Gene Polymorphisms and the Risk of Hypertension in the Chinese Han Population

BackgroundHypertension is rising as a major public health burden around the world. This study explored the association between single-nucleotide polymorphisms (SNPs) in the adenosine triphosphate (ATP)-Binding Cassette Subfamily A1 (ABCA1) gene and hypertension among Chinese Han adults.MethodA total of 2,296 Han Chinese in southeast China were recruited for this study. We collected medical reports, lifestyle details, and blood samples from individuals. The polymerase chain reaction-ligase detection reaction (PCR-LDR) method was used to detect the genotypes of these SNPs in the ABCA1 gene.ResultsAfter adjusting some covariates, the additive and recessive models of the rs2472510 and rs2515614 were significantly associated with hypertension. The haplotypes TCTA (rs2297406-rs2472433-rs2472510-rs2515614) were associated with high SBP, and the haplotypes CCTA, TCTA, and TTTA were associated with high diastolic blood pressure (DBP).ConclusionThe results of the relationship between the polymorphisms of rs2297406, rs2472433, rs2472510, and rs2515614 in ABCA1 and hypertension in southeastern China would provide a theoretical basis for genetic screening and disease prevention.

Correlation of MIF-AS1 polymorphisms with the risk and prognosis of gastric cancer

BackgroundThe most studied genetic polymorphisms associated with gastric cancer (GC) risk are located in protein-coding genes. However, the localization of these in long non-coding RNAs (lncRNAs) has not been fully studied. We aim to investigate the associations of Long non-coding RNA macrophage migration inhibitory factor antisense RNA1(Lnc-MIF-AS1) five polymorphisms (rs755622, rs17004044, rs2070767, rs1007889, rs2000468) with the risk and prognosis of GC. MethodsA total of 844 GC patients and 871 controls were included in the study. Genotyping was carried out using polymerase chain reaction-ligase detection reaction (PCR-LDR) technology. Odds ratios (ORs) and 95% confidence intervals (CIs) generated from unconditional logistic regression, were applied to quantify the effects of MIF-AS1 gene SNPs on GC risk. Log-rank test and Cox regression analysis were fitted to estimate hazard ratios (HRs) to quantify the effects of MIF-AS1 gene SNPs on GC prognosis. ResultsSignificant associations were identified between MIF-AS1 rs17004044 variants and GC group in the codominant, dominant and additive models (OR = 2.843, P = 0.010; OR = 1.370, P = 0.004; and OR = 1.386; P = 0.001). In addition, association between rs17004044 variants and survival of GC was extremely observed (TC HR = 2.02 (1.21–3.37) P = 0.007, CC HR = 5.61 (2.12–14.83), P = 0.001). ConclusionMIF-AS1 polymorphism rs17004044 contributes to increased predisposition and prognosis to GC.

MDM4 polymorphisms associated with the risk but not the prognosis of esophageal cancer in Cixian high-incidence region from northern China.

The mouse double minute 4 (MDM4) may contribute to tumorgenesis by inhibiting p53 tumor suppressor activity. This study was designed to investigate whether MDM4 polymorphisms could affect susceptibility to esophageal squamous cell carcinoma (ESCC) and the survival of ESCC patients in a population from Cixian high-incidence region of northern China, which has not been explored. MDM4 rs1380576 and rs4245739 were genotyped by polymerase chain reaction-ligase detection reaction (PCR-LDR) in 568 ESCC patients and 578 controls. Compared to rs1380576 C/C genotype, C/G genotype was associated with decreased risk of ESCC (odds ratio [OR]=0.761, 95% confidence interval [CI]=0.595-0.973). Compared to rs4245739 A/A genotype, A/C or C/C genotype was related to increased susceptibility to ESCC (OR=1.551, 95% CI=1.001-2.402). Individuals with GC haplotype had significantly higher risk of ESCC than those with CA or GA haplotype (OR=1.598, 95% CI=1.048-2.438). Neither rs1380576 nor rs4245739 influenced the survival of ESCC patients. rs1380576 and rs4245739 may be used to predict susceptibility to ESCC for population in Cixian high-incidence region.

Interlukin-27 rs153109 polymorphism confers the susceptibility and prognosis of aplastic anemia in Chinese population.

Accumulating evidence has indicated that interleukin (IL)-27 and its gene polymorphisms exert pivotal impact on several autoimmune disorders. This research intended to investigate the relationship between IL-27 rs153109 polymorphism with risk and prognosis for aplastic anemia. IL-27 rs153109 polymorphism was detected with polymerase chain reaction-ligase detection reaction in 238 patients with aplastic anemia and 215 normal individuals. Enzyme-linked immunosorbent assays were applied to measure the plasma level of IL-27. Frequencies of rs153109 AA and GG genotype were statistically higher in aplastic anemia patients compared to controls. Similar results were observed when further divided patients into nonsevere and severe ones. That means carriers of AA and GG genotype are accompanied by an increased risk of developing aplastic anemia. Plasma IL-27 levels of aplastic anemia patients were remarkably elevated than normal group and had positive relation with disease severity. Furthermore, patients with AA genotype had obviously higher IL-27 levels than ones with AG and GG genotype. Moreover, patients carrying AA genotype exhibited a poorer reaction to immunosuppressive therapy and were more prone to clonal evolution. IL-27 rs153109 polymorphism confers genetic predisposition to aplastic anemia and influences disease prognosis, potentially by regulating IL-27 expression, which help broaden potential pathogenesis of aplastic anemia. Specifically, for patients with AA genotype, more aggressive therapeutic strategies such as hematopoietic stem cells transplantation are warranted.

Association of CDKN2A/CDKN2B Gene Polymorphisms with Increased Susceptibility to Intracranial Aneurysm in a Chinese Han Population.

ObjectiveSeveral studies have reported that single-nucleotide polymorphisms (SNPs) of the CDKN2A/CDKN2B gene on chromosome 9p21.3 are associated with increased risk of intracranial aneurysm (IA). However, the association between IAs and SNPs of CDKN2A/CDKN2B in Chinese Han people is yet to be evaluated. This study examined the association of the SNPs rs10811661 and rs4977574 with IA in the Chinese Han population.MethodsA total of 595 IA patients and 600 sex- and age-matched controls were enrolled in the study. Peripheral blood was collected and stored at –80°C until use. CDKN2A/CDKN2B was identified using polymerase chain reaction–ligase detection reaction. SNP genotyping was performed for rs10811661 and rs4977574 using a MassArray system. Associations between these two SNPs and IAs was tested with χ2 or Fisher’s exact tests and multivariate logistic regression.Resultsrs10811661 and rs4977574 were significantly associated with IA. The frequency of rs10811661-T in IA was higher than in controls (OR 1.26, 95% CI 1.07–1.49; P<0.01). There was no significant difference in frequency of haplotype between control subjects and IA patients.Conclusionrs10811661 and rs4977574 on 9p21.3 were strongly associated with genetic susceptibility to IA in the Chinese Han population, which emphasizes a need for further investigation.

TIM-3 polymorphism is involved in the progression of esophageal squamous cell carcinoma by regulating gene expression.

The T-cell immunoglobulin and mucin domain containing molecule 3 (TIM-3), a crucial immune regulatory molecule, is an emerging immune checkpoint target for cancer therapy. Our study aimed to investigate the association between TIM-3 polymorphisms (rs10053538 C > A, rs10515746 C > A, and rs1036199 A > C) and the susceptibility and prognosis of esophageal squamous cell carcinoma (ESCC). We further detect the effects of polymorphisms on TIM-3 expression. Two independent case-control sets (population-based and hospital-based sets) were performed in total 994 ESCC patients and 998 controls. TIM-3 polymorphisms were genotyped by polymerase chain reaction-ligase detection reaction (PCR). Survival data were available for 198 patients who received platinum-based chemotherapy after surgery. The regulation on TIM-3 expression by the polymorphisms was investigated in 35 patients using real-time quantitative PCR. The association between mRNA level of TIM-3 and survival was detected by using Kaplan-Meier plotter database. We found that for rs10053538 C > A polymorphisms, A allele was associated with significant increased risk of ESCC (odds ratios [OR] = 1.34, 95%CI = 1.05-1.72), and CA/AA genotypes enhanced susceptibility to ESCC for smokers (adjusted OR = 1.61, 95%CI = 1.00-2.59). The patients with AA genotypes had significantly poor prognosis (adjusted HR = 4.98, 95%CI = 1.14-21.71). The patients carrying CA/AA genotypes had significantly higher mRNA levels of TIM-3 than those carrying the CC genotype. Furthermore, high mRNA level of TIM-3 had a shorter overall survival in patients (HR = 2.56, 95%CI = 1.04-6.28). For rs10515746 C > A and rs1036199 A > C polymorphisms, there were no statistical correlation with the progression of ESCC. These data demonstrate that rs10053538 C > A polymorphisms may be associated with the susceptibility and prognosis of ESCC patients through regulating expression of TIM-3.

PARP1 rs1136410 C/C genotype associated with an increased risk of esophageal cancer in smokers.

DNA repair system plays a crucial role in maintaining genomic integrity and stability and in protecting against cancer. Poly(ADP-ribose) polymerase 1 (PARP1) functions as a key enzyme in the base excision repair (BER) pathway. Single nucleotide polymorphism (SNP) that could affect the function or expression of PARP1 gene might be associated with the risk of cancer. This study was designed to evaluate the association between PARP1 SNPs and the susceptibility to esophageal squamous cell carcinoma (ESCC) in a population from Cixian, a high incidence region from northern China. In 574 ESCC patients and 577 controls, PARP1 rs1136410 and rs8679 SNPs were genotyped by polymerase chain reaction ligase detection reaction (PCR-LDR) method. Upper gastrointestinal cancer (UGIC) family history enhanced the risk of ESCC (the sex-, age- and smoking status-adjusted OR 1.355, 95% CI 1.071-1.715). Overall, rs1136410 and rs8679 SNPs did not modify the risk of ESCC. When stratified by sex, age, smoking status and UGIC family history, the rs1136410 C/C genotype was associated with an increased risk of ESCC in smokers compared to T/T or T/C genotype (the sex-, age- and UGIC family history-adjusted OR 1.696, 95% CI 1.032-2.787). In Cixian high incidence region from northern China, smokers with rs1136410 C/C genotype might have higher susceptibility to ESCC than those with T/T or T/C genotype. These high-risk individuals receiving periodic upper gastrointestinal fiber tests might facilitate early detection and early treatment of ESCC.

Role of CASP7 polymorphisms in noise-induced hearing loss risk in Han Chinese population

Genetic factors and gene-environment interaction may play an important role in the development of noise induced hearing loss (NIHL). 191 cases and 191 controls were selected by case–control study. Among them, case groups were screened from workers exposed to noise in binaural high-frequency hearing thresholds greater than 25 dB (A). Workers with hearing thresholds ≤ 25 dB (A) in any binaural frequency band were selected to the control group, based on matching factors such as age, exposure time to noise, and operating position. The blood samples from two groups of workers were subjected to DNA extraction and SNP sequencing of CASP3 and CASP7 genes using the polymerase chain reaction ligase detection reaction method. Conditional logistic regression correction was used to analyze the genetic variation associated with susceptibility to NIHL. There was an association between rs2227310 and rs4353229 of the CASP7 gene and the risk of NIHL. Compared with the GG genotype, the CC genotype of rs2227310 reduced the risk of NIHL. Compared with CC genotype, the TT genotype of rs4353229 reduced the risk of NIHL. Workers carrying the rs2227310GG and rs4353229CC genotype had an increased risk of NIHL compared to workers without any high-risk genotype. There were additive interaction and multiplication interaction between CASP7rs2227310 and CNE, and the same interaction between CASP7rs4353229 and CNE. The interaction between the CASP7 gene and CNE significantly increased the risk of NIHL. The genetic polymorphisms of CASP7rs2227310GG and CASP7rs4353229CC were associated with an increased risk of NIHL in Han Chinese population and have the potential to act as biomarkers for noise-exposed workers.

Genetic polymorphisms of Cathepsin B are associated with gastric cancer risk and prognosis in a Chinese population.

Genetic polymorphisms are believed to represent a key aspect of predisposition to gastric cancer (GC). Therefore, considering the important role of Cathepsin B (CTSB) in promoting cancer onset and development, it could be very worthful to explore the function of CTSB-related genetic polymorphisms in GC. In this study, we investigated the correlation of CTSB-related polymorphisms (rs9009A>T, rs6731T>C, rs1293303G>C, rs1874547C>T, rs3779659C>T, rs17814426C>T and rs148669985C>T) with GC risk and prognosis in a case-control study of 994 cases and 1000 controls. All tag single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-ligase detection reaction (PCR-LDR) sequencing technology. The results indicated rs9009, rs6731 and rs17814426 correlated with decreased risks of GC (HR = 0.97, p< 0.001; HR = 0.86, P= 0.019; HR = 0.85, P= 0.017; respectively). Stratification analysis further showed rs17814426 variant genotypes correlated with earlier T stage (p= 0.044). In addition, GC patients carrying the C allele of rs6371 had better overall prognosis (HR = 0.62, 95%CI = 0.44-0.88). Our results firstly suggested the importance of CTSB-related polymorphisms on GC which could predict GC risk and prognosis.

Cytochrome P450 27B1 Gene Polymorphism rs10877012 and rs4646536 in Patients with Systemic Lupus Erythematosus

Systemic lupus erythematosus is a severe inflammatory connective tissue disease induced by autoimmunity. The cytochrome p450 27B1 gene, activating Vitamin D precursor 25-hydroxyvitamin D into 1,25-dihydroxyvitamin D in immunity cells resulted in autoimmune disorders. This study was assessing the correlation and clinical pathological characteristics relationship between the cytochrome p450 27B1 gene polymorphism rs10877012/rs4646536 and systemic lupus erythematosus to provide a rationale for determining the role that cytochrome p450 27B1 gene polymorphism plays in systemic lupus erythematosus. In this study, we investigated the association of rs10877012 (T/G) polymorphism with systemic lupus erythematosus susceptibility in 156 patients with systemic lupus erythematosus compared to 156 healthy population, both groups came from the same Mendelian population by conformity to Hardy Weinberg equilibrium. DNA was extracted from peripheral leukocytes and analyzed for the polymorphism using the polymerase chain reaction-ligase detection reaction method. We found an association between the presence of the T allele at the polymorphic site (odds ratio=2.94; 95 % confidence interval 1.77–4.86; <0.0001) and a decreased colorectal cancer incidence. rs10877012 polymorphism was associated with arthritis and positive Anti-double stranded DNA antibody and increased C-reactive protein happened in patients with systemic lupus erythematosus.

PARP1 Gene Polymorphisms and the Prognosis of Esophageal Cancer Patients from Cixian High-Incidence Region in Northern China.

Objective:Poly (ADP-ribose) polymerase 1 (PARP1), as a key enzyme in the base excision repair pathway, plays a crucial role in tumorigenesis and progression. This study aimed to assess whether polymorphisms of PARP1 gene could be used as predictive biomarkers for the survival of esophageal squamous cell carcinoma (ESCC) patients from Cixian high-incidence region in northern China. Methods:In 203 ESCC patients with survival information, PARP1 rs1136410 T/C and rs8679 T/C single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction ligase detection reaction (PCR-LDR) method. All statistical analyses were performed using the SPSS ver. 22.0 software package (SPSS, Chicago, IL, USA). Results:The mean age ± standard deviation of the ESCC patients was 60.4 ± 7.9 years. There was no significant relation of sex, age, smoking status and upper gastrointestinal cancer family history with the survival time of the ESCC patients. The mean survival time of rs1136410 T/T, T/C and C/C genotype carriers were 43.3, 42.3 and 46.6 months, respectively. The rs1136410 was not associated with the survival time of the ESCC patients. For rs8679, the mean survival time of T/T genotype carriers was 43.7 months, which was not significantly different from that of the patients with T/C genotype (42.1 months).Conclusion:In Cixian high-incidence region from northern China, rs1136410 and rs8679 SNPs might not be used to predict survival of ESCC patients. There is a need to explore whether other SNPs of PARP1 gene have an effect on prognosis of ESCC patients.

TOMM40 and APOE variants synergistically increase the risk of Alzheimer's disease in a Chinese population.

The apolipoprotein E (APOE) ε4 allele is a strong risk factor for Alzheimer's disease (AD) in Caucasian and African American populations. It suggests that other genetic factors may modulate AD pathogenesis in Chinese populations, among which the frequency of this allele is reduced but the AD prevalence is maintained. The translocase of outer mitochondrial membrane 40 (TOMM40), which is located adjacent to APOE, may play an APOE-dependent role in modulating AD pathogenesis. This work aimed to investigate whether TOMM40 polymorphisms modulate AD risk independently of, or in conjunction with APOE polymorphisms in Chinese populations. We conducted a case-control study including 834 patients with AD recruited from the Memory Clinic and 643 cognitively normal participants recruited from the community. The Taqman SNP method was used for APOE genotyping, while TOMM40 polymorphism genotyping was conducted via a polymerase chain reaction-ligase detection reaction. The TOMM40 rs10119 and rs71352238 alleles were associated with AD independently of the patient APOE status. The rs10119 AA genotype and rs71352238 CC genotype were risk genotypes of AD. Individuals carrying a TOMM40 rs10119 GG/APOE ε4+ (OR, 3.73; 95% CI 1.49-9.37; P = 0.005), TOMM40 rs10119 AG/APOE ε4+ (OR, 4.16; 95% CI 3.30-5.24; P < 0.001), or TOMM40 rs10119 AA/APOE ε4+ (OR, 14.78; 95% CI 8.56-25.54; P < 0.001) genotype exhibited a significantly higher AD risk. Those carrying a TOMM40 rs71352238 TT/APOE ε4+ (OR, 3.82; 95% CI 2.32-6.29; P < 0.001), TOMM40 rs71352238 CT/APOE ε4+ (OR, 4.40; 95% CI 3.46-5.56; P < 0.001), or TOMM40 rs71352238 CC/APOE ε4+ (OR, 14.02; 95% CI 7.81-25.17; P < 0.001) genotype also exhibited a significantly increased AD risk. This study provides invaluable insights into the mechanisms underlying the prevalence of AD in Chinese populations, and supports that simultaneous TOMM40 and APOE genotyping in the clinical setting may identify individuals at high risk of developing AD.

Genetic variants and expression of the TIM-3 gene are associated with clinical prognosis in patients with epithelial ovarian cancer

ObjectivePolymorphisms of T cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) were reported to be associated with cancer risk and patients' survival. This study aims to investigate the correlation of TIM-3 polymorphisms with susceptibility to epithelial ovarian cancer (EOC) and patients' outcomes. MethodsA total of 700 EOC patients and 710 healthy controls from North China were included. The polymorphisms (rs10053538, rs10515746 and rs1036199) were genotyped using the polymerase chain reaction/ligase detection reaction (PCR-LDR) method. Survival data were available for 339 patients after cytoreductive surgery. The expression level of TIM-3 was detected by real-time quantitative PCR (RT-qPCR). The prognostic value of TIM3 in EOC patients was assessed using the Kaplan-Meier plotter database. ResultsThe results showed that none of the TIM3 polymorphisms were associated with the risk of developing EOC. Patients with the rs10053538 CA + AA genotype had worse PFS and OS than those with the CC genotype (HR = 1.49, 95% CI = 1.05–2.09, P = 0.024 and HR = 1.57, 95%CI = 1.09–2.26, P = 0.017, respectively). The RT-qPCR results showed that the expression levels of TIM-3 mRNA in EOC tissues with the rs10053538CA + AA genotypes were significantly higher than those with the CC genotype (P = 0.006). Analysis using the Kaplan-Meier plotter database showed that high expression of TIM-3 mRNA was significantly associated with shorter PFS and OS in EOC patients (HR = 1.57, 95%CI = 1.29–1.91, P < 0.001 and HR = 1.31, 95% CI = 1.06–1.63, P = 0.013, respectively). ConclusionsTIM-3 polymorphisms were not associated with risk of developing EOC. Both rs10053538 and the expression level of TIM-3 mRNA may be associated with its clinical outcome in EOC patients.