RNA-binding proteins potentially regulate alternative splicing of immune/inflammatory-associated genes during the progression of generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a rare but severe form of psoriasis. However, the pathogenesis of GPP has not been fully elucidated. Although RNA-binding proteins (RBPs) and the alternative splicing (AS) process are essential for regulating post-transcriptional gene expression, their roles in GPP are still unclear. We aimed to elucidate the regulatory mechanisms to identify potential new therapeutic targets. Here, We analyzed an RNA sequencing (RNA-seq) dataset (GSE200977) of peripheral blood mononuclear cells (PBMCs) of 24 patients with GPP, psoriasis vulgaris (PV), and healthy controls (HCs) from the Gene Expression Omnibus (GEO) database. We found that the abnormal alternative splicing (AS) events associated with GPP were mainly "alt3p/alt5p", and 15 AS genes were differentially expressed. Notably, the proportions of different immune cell types were correlated with the expression levels of regulatory alternatively spliced genes (RASGs): significant differences were observed in expression levels of DTD2, NDUFAF3, NBPF15, and FBLN7 in B cells and ARFIP1, IPO11, and RP11-326L24.9 in neutrophils in the GPP samples. Furthermore, We identified 32 differentially expressed RNA-binding proteins (RBPs) (18 up-regulated and 14 down-regulated). Co-expression networks between 14 pairs of differentially expressed RBPs and RASGs were subsequently constructed, demonstrating that these differentially expressed RBPs may affect the progression of GPP by regulating the AS of downstream immune/inflammatory-related genes such as LINC00989, ENC1 and MMP25-AS1. Our results were innovative in revealing the involvement of inflammation-related RBPs and RASGs in the development of GPP from the perspective of RBP-regulated AS.

Association Between CYP2D7 and TCF20 Polymorphisms and Coronary Heart Disease.

One of the causes of coronary heart disease (CHD) is genetic factors. In this study, we explored the relationship between CYP2D7 and TCF20 gene polymorphisms and the risk of CHD in the Han Chinese population. Three single nucleotide polymorphisms (CYP2D7 rs1800754, CYP2D7 rs2743461, and TCF20 rs760648) were selected and genotyped from 490 cases and 480 controls. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between CYP2D7 and TCF20 polymorphisms and the risk of CHD. The association between clinical indicators and polymorphisms was analyzed using one-way ANOVA and Tukey's HSD. The SNP-SNP interactions were obtained by performing multifactor dimensionality reduction (MDR). CYP2D7 rs1800754 and rs2743461 were closely associated with increased risk of CHD (alleles: p = 0.014, p = 0.031). Stratified analysis showed that CYP2D7 rs1800754 and rs2743461 were associated with an increased risk of CHD in men, age > 60 years, BMI ≥ 24, and smoking. Rs1800754 is also associated with an increased risk of CHD associated with alcohol consumption. In addition, TCF20 rs760648 was associated with a reduced risk of CHD in patients aged ≤ 60 years and with CALs. A significant association was found between CYP2D7 rs1800754 and rs2743461 genotypes and levels of UREA, Cr, and LDL-C; TCF20 rs760648 genotypes and levels of RBC. The MDR analysis showed that the three-locus interaction model was the best in the multi-locus model. In conclusion, CYP2D7 rs1800754 and rs2743461 polymorphisms were associated with CHD risk.

Genetic Variability of CYP4F2, CYP2D6, CYP2E1, and ACE in the Chinese Yi Population.

Genetic polymorphisms of very important pharmacogenes (VIP) are a significant factor contributing to inter-individual variability in drug therapy. The purpose of this study was to identify significantly different loci in the Yi population and to enrich their pharmacogenomic information. 54 VIP variants were selected from the Pharmacogenomics Knowledge Base (PharmGKB) and genotyped in 200 Yi individuals. Then, we compared their genotype distribution between the Yi population and the other 26 populations using the χ2 test. Compared with the other 26 populations, the genotype frequencies of 4 single nucleotide polymorphisms (SNPs), rs2108622 (CYP4F2), rs1065852 (CYP2D6), rs2070676 (CYP2E1), and rs4291 (ACE), had significant differences in the Yi population. For example, the TT genotype frequency of rs2108622 (8.1%) was higher than that of African populations, and the AA genotype frequency of rs1065852 (27.3%) was higher than that of other populations except East Asians. We also found that the Yi populations differed the least from East Asians and the most from Africans. Furthermore, the differences in these variants might be related to the effectiveness and toxicity risk of using warfarin, iloperidone, cisplatin cyclophosphamide, and other drugs in the Yi population. Our data complement the pharmacogenomic information of the Yi population and provide theoretical guidance for their personalized treatment.

The modulator role of Urtica dioica on deleterious effects of retinoic acid high doses on histological parameters and fertilization of rats.

Aim: This study purposed to evaluate the modulator and protective role of Urtica dioica (UD) extract against deleterious effects of retinoic acid (RA) high doses on histological parameters and fertilization of rats. Materials and methods: For the in-vivo phase, 60 female Wistar rats were divided into 6 identical groups as 1) control, 2) 25 mg/kg RA, 3) 25 mg/kg UD extract, 4) 50 mg/kg UD extract, 5) UD extract (25 mg/kg) + RA (25 mg/kg), and 6) UD extract (50 mg/kg) + RA (25 mg/kg). Biochemical parameters, including luteinizing hormone (LH), folliclestimulating hormone (FSH), malondialdehyde (MDA) levels, superoxide dismutase (SOD), and catalase (CAT) activities, were measured. In the in-vitro phase, oocytes were obtained from 10 female rats without injection. In addition to the mentioned parameters, histological parameters (oocytes in various stages) and the results of IVM, IVF, and embryo developments were assessed and compared among the groups with the use of one-way ANOVA and Tukey's post hoc tests. Results: The high dosage of RA significantly reduced the LH and FSH levels; however, UD alone and with RA increased the hormone levels in rats. Regarding the reactive oxygen species (ROS) activity levels in rats' blood samples, RA increased the MDA and decreased the SOD and CAT levels. Treatment with UD extract (UD + RA groups) significantly improved the parameters mentioned, showing UD's antioxidant effect. The rate of oocyte maturation, 2-cell-4-cell and 4-cell-8-cell embryos, and blastocyst formation increased significantly in the groups in which UD extracts were administered compared to the control and RA groups. Furthermore, the increases were significant in the UD + RA groups compared to the RA group. Conclusion: UD extract can significantly reduce RA high doses side effects on histological parameters and fertilization of rats and has the protective potential against RA deleterious effects.

Case report: Gene mutation analysis and skin imaging of isolated café-au-lait macules.

Background: Café-au-lait macules (CALMs) are common birthmarks associated with several genetic syndromes, such as neurofibromatosis type 1 (NF1). Isolated CALMs are defined as multiple café-au-lait macules in patients without any other sign of NF1. Typical CALMs can have predictive significance for NF1, and non-invasive techniques can provide more accurate results for judging whether café-au-lait spots are typical. Objectives: The study aimed to investigate gene mutations in six Chinese Han pedigrees of isolated CALMs and summarize the characteristics of CALMs under dermoscopy and reflectance confocal microscopy (RCM). Methods: In this study, we used Sanger sequencing to test for genetic mutations in six families and whole exome sequencing (WES) in two families. We used dermoscopy and RCM to describe the imaging characteristics of CALMs. Results: In this study, we tested six families for genetic mutations, and two mutations were identified as novel mutations. The first family identified [NC_000017.11(NM_001042492.2):c.7355G>A]. The second family identified [NC_000017.11(NM_001042492.2):c.2739_2740del]. According to genotype-phenotype correlation analyses, proband with frameshift mutation tended to have a larger number of CALMs and a higher rate of having atypical CALMs. Dermoscopy showed uniform and consistent tan-pigmented network patches with poorly defined margins with a lighter color around the hair follicles. Under RCM, the appearance of NF1 comprised the increased pigment granules in the basal layer and significantly increased refraction. Conclusion: A new heterozygous mutation and a new frameshift mutation of NF1 were reported. This article can assist in summarizing the properties of dermoscopy and RCM with CALMs.

Polymorphisms in IL-1A are associated with endometrial cancer susceptibility among Chinese Han population: A case-control study.

Endometrial cancer (EC) is one of the most common malignant tumours of the female genital tract, and it has become a serious malignant disease of the female genital tract in China. Existing researches have revealed the association between polymorphisms of IL-1A and several gynaecological diseases. In this research, we analysed the association between IL-1A gene polymorphisms and endometrial cancer susceptibility in Chinese female population. A total of 81 patients and 198 healthy people were selected. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression. Genetic models and analyses showed that IL-1A rs3783550 TT and rs3783546 CC increased the risk of endometrial cancer under the recessive model, respectively (rs3783550: OR = 2.80, 95%CI: 1.32-5.92, p = .008; rs3783546: OR = 2.79, 95%CI: 1.32-5.89, p = .008). In the recessive model, we also found that both IL-1A rs1609682 and IL-1A rs3783521 increased the risk of endometrial cancer, respectively (rs1609682: OR = 2.79, 95%CI: 1.32-5.89, p = .0081; rs3783521: OR = 2.80, 95%CI: 1.32-5.92, p = .008). Haplotype analysis was performed that did not reveal any significant results. In summary, IL-1A rs3783550, rs3783546, rs1609682 and rs3783521 polymorphisms may be associated with an increased risk of endometrial cancer in Chinese female populations.

Gene polymorphism of cytochrome P450 significantly affects lung cancer susceptibility.

BACKGROUND: Cytochrome P450 (CYPs) are heme proteins involved in the metabolism of a variety of endogenous and exogenous substances and play an important role in the carcinogenesis mechanisms of environmental and hereditary factors. The objective of this study was to investigate how polymorphisms of CYPs correlate with lung cancer (LC) susceptibility. METHODS: Six single nucleotide polymorphisms (SNPs) were genotyped in this study. The chi-square test and unconditional logistic regression model were used to evaluate the correlation between SNPs and LC susceptibility. The expressions and survival data of genes in patients with LC were mined using Oncomine and Kaplan-Meier Plotter database. RESULTS: Four SNPs were found to be significantly associated with the risk of LC development (P < 0.05). The most significant correlation was that the A allele and AA genotype of CYP2D6 rs1065852 were associated with increased risk of LC development (adjusted odds ratio [OR] = 1.35, 95% confidence interval [95%CI] = 1.13-1.60, P = 9.04e-4; OR = 1.83, 95%CI = 1.29-2.59, P = 0.001 respectively). Similar association of this variant was also found in the subgroups of male patients, cases in III-IV stages, positive lymph node, squamous cell carcinomas and adenocarcinomas. Whereas rs1065852 was considered as protective factor in females (adjusted OR = 0.33, 95% CI = 0.16-0.70, P = 0.004). In stratified analyses, the association of CYP24A1 rs2762934, CYP24A1 rs6068816, CYP20A1 rs2043449 polymorphism with LC risk appeared stronger in some subgroups. CYP2D6, CYP24A1 and CYP20A1 are overexpressed in some pathological types of LC (P < 0.05), and high levels of CYP2D6 and CYP20A1 indicate poor and good prognosis of LC, respectively. CONCLUSION: This study revealed that rs1065852, rs2043449, rs2762s934, and rs6068816 of CYPs were associated with LC susceptibility in the Northwestern Chinese Han population; CYP2D6 and CYP20A1 were overexpressed and correlated with prognosis of LC.

A case-control study of the association between the EGFR gene and glioma risk in a Chinese Han population.

The Epidermal Growth Factor Receptor gene has been reported to be involved in the progression of gliomas which is one of the deadliest primary brain tumors in humans. To determine potential association between EGFR and glioma risk, we performed a case-control study with 394 glioma patients and 298 cancer-free controls in which captured a total of 8 tag single nucleotide polymorphisms of EGFR gene from Xi'an, China. SPSS 19.0 statistical packages, χ2 test, genetic model analysis and SHEsis software platform were analyzed s the variants in EGFR gene associations with glioma risk. For five different inheritance models analyzed, the following genotypes were associated with increased glioma risk. In the codominant model, genotype CC (rs730437, OR = 1.93, p = 0.024; rs1468727, OR = 2.02, p = 0.007); In the dominant model, genotype CA and CC (rs730437, OR = 1.45, p = 0.026), genotype GA and AA (rs845552, OR = 1.40, p = 0.044); In the recessive model, genotype CC (rs730437, OR = 1.64, p = 0.026; rs1468727, OR = 1.87, p = 0.002); In the additive model, genotype CC (rs730437, OR = 1.32, p = 0.006; rs1468727, OR = 1.39, p = 0.005), genotype GG (rs11506105, OR = 1.32, p = 0.02) and genotype AA (rs845552, OR = 1.27, p = 0.04). Our study indicated that 8 mutants located in EGFR gene were risk-conferring factors, larger and different populations with EGFR polymorphisms are required to verify these associations.

Genetic analysis of drug metabolizing phase-I enzymes CYP3A4 in Tibetan populations.

The enzymatic activity of CYP3A4 results in broad interindividual variability in response to certain pharmacotherapies. The present study aimed to screen Tibetan volunteers for CYP3A4 genetic polymorphisms. Previous research has focussed on Han Chinese patients, while little is known about the genetic variation of CYP3A4 in the Tibetan populations. Here, we adopted DNA sequencing to investigate the promoter, exons and surrounding introns, and 3'-untranslated region of the CYP3A4 gene in 96 unrelated healthy Tibetan individuals.We identified 20 different CYP3A4 polymorphisms in the Tibetan population, including two novel variants (21824 A>G and 15580 G>C). In addition, we also determined the allele frequencies of CYP3A4*1A and CYP3A4*1H were 82.29% and 28.13%, respectively. CYP3A4*1P and *1G were relatively rare with frequencies of only 1.04% and 0.52%, respectively. Our results provide information on CYP3A4 polymorphisms in Tibetan individuals which may help to optimize pharmacotherapy effectiveness by providing personalized medicine to this ethnic group.

Single-nucleotide polymorphisms of MMP2 in MMP/TIMP pathways associated with the risk of alcohol-induced osteonecrosis of the femoral head in Chinese males: A case-control study.

The proportion of alcohol-induced osteonecrosis of the femoral head (ONFH) in all ONFH patients was 30.7%, with males prevailing among the ONFH patients in mainland China (70.1%). Matrix metalloproteinase 2 (MMP2), a member of the MMP gene family, encodes the enzyme MMP2, which can promote osteoclast migration, attachment, and bone matrix degradation. In this case-control study, we aimed to investigate the association between MMP2 and the alcohol-induced ONFH in Chinese males.In total, 299 patients with alcohol-induced ONFH and 396 healthy controls were recruited for a case-control association study. Five single-nucleotide polymorphisms within the MMP2 locus were genotyped and examined for their correlation with the risk of alcohol-induced ONFH and treatment response using Pearson χ test and unconditional logistic regression analysis. We identified 3 risk alleles for carriers: the allele "T" of rs243849 increased the risk of alcohol-induced ONFH in the allele model, the log-additive model without adjustment, and the log-additive model with adjustment for age. Conversely, the genotypes "CC" in rs7201 and "CC" in rs243832 decreased the risk of alcohol-induced ONFH, as revealed by the recessive model. After the Bonferroni multiple adjustment, no significant association was found. Furthermore, the haplotype analysis showed that the "TT" haplotype of MMP2 was more frequent among patients with alcohol-induced ONFH by unconditional logistic regression analysis adjusted for age.In conclusion, there may be an association between MMP2 and the risk of alcohol-induced ONFH in North-Chinese males. However, studies on larger populations are needed to confirm this hypothesis; these data may provide a theoretical foundation for future studies.

Association of the miR-17-5p variants with susceptibility to cervical cancer in a Chinese population.

MicroRNAs (miRNAs) are key regulators of gene expression; however, the extent to which single nucleotide polymorphisms (SNPs) interfere with miRNA gene regulation and affect cervical cancer (CC) susceptibility remains largely unknown. Here, we systematically analyzed miRNA-related SNPs and their association with CC risk, and performed a case-control study of miR-17-5p SNPs and CC risk in a Chinese population. Sixteen SNPs were genotyped in 247 CC cases and 285 controls. Three were associated with CC risk (p < 0.05): the minor allele (A) of rs217727 in H19 increased risk (OR = 1.53, p = 0.002), while the minor alleles (T) of rs9931702 and (T) of rs9302648 in AKTIP decreased CC risk (p = 0.018, p = 0.014). Analysis of the SNPs after stratification based on CC clinical stage and subtype revealed that rs1048512, rs6659346, rs217727, rs9931702, and rs9302648 were associated with CC risk in clinical stages I-II; rs2862833, rs2732044, rs1030389, and rs1045935 were associated with CC risk in clinical stages III-IV; and rs217727, rs9931702, and rs9302648 were associated with CC risk in squamous carcinomas. These data could serve as a useful resource for understanding the miR-17 function, identification of miRNAs associated with CC, and development of better CC screening strategies.

Polymorphism in the IL4R gene and clinical features are associated with glioma prognosis: Analyses of case-cohort studies.

Inflammatory gene polymorphisms may be associated with glioma risk. The purpose of this study was to analyze effects of certain inflammatory gene and some clinical factors on patient survival.The clinical information of 269 glioma patients conceived operation from September 2010 to May 2014 to decide the 1-, 3-year survival rates according to follow-up results and analyze age, gender, the WHO classification, extent of surgical resection, radiotherapy and chemotherapy factors effects on prognosis. Survival distributions were estimated by using the Kaplan-Meier method and difference in the survival was tested using the log-rank test. To estimate the association between the IL4, IL13, IL10, IL4R SNPs, and PFS and OS in glioma, the HR and 95% CI were calculated by univariate Cox proportional hazards model. Multivariate Cox model were performed to compute adjusted HR and 95% CI. All data was analyzed with SPSS17.0 package. Extent of surgical resection, chemotherapy, and age are an important factor in glioma overall survival and progression-free survival overall. Extent of surgery and chemotherapy are important factors in astrocytoma overall survival. Univariate analysis showed that IL4R rs1801275 was significantly associated with overall survival of glioma and astrocytoma patients (P < 0.05). Multivariate Cox regression analysis showed that IL4R rs1801275 GG genotype could increase the death risk of glioma and astrocytoma patients (Glioma: hazard ratio [HR]: 4.897, 95% confidence limits [95% CI]: 1.962-12.222, P = 0.001; Astrocytoma: HR: 15.944, 95% CI: 4.019-63.253, P < 0.05).Our research results showed that extent of surgical resection, age, and chemotherapy affect the prognosis of glioma. The IL4R gene may affect the survival of glioma patients.

Genetic polymorphisms analysis of drug-metabolizing enzyme CYP2C9 in the Uyghur population.

Genetic variations in cytochrome P450 2C9 are known to contribute to interindividual and interethnic variability in response to clinical drugs, but little is known about the genetic variation of CYP2C9 in the Uyghur population. We directly sequenced the whole CYP2C9 gene in 96 unrelated, healthy Uyghur from Xinjiang Uygur Autonomous Region of China and screened for genetic variants in the promoter, exons, introns and 3'-UTR. Thirty five previously reported alleles and six genotypes were detected in this study. The allele frequencies of CYP2C9*1, *2, *11, *12, *29 and *33 were 89.58, 7.81, 0.52, 0.52, 1.04 and 0.52%, respectively. We detected one non-synonymous novel variant at position 329 from Arg to Cys and this mutation is predicted to be intolerant by SIFT. Our results provide basic information about CYP2C9 alleles in Uyghur, which may help to optimize pharmacotherapy effectiveness by providing personalized medicine to this ethnic group.

Change in soil organic carbon between 1981 and 2011 in croplands of Heilongjiang Province, northeast China.

BACKGROUND: Soil organic carbon (SOC) is fundamental for mitigating climate change as well as improving soil fertility. Databases of SOC obtained from soil surveys in 1981 and 2011 were used to assess SOC change (0-20 cm) in croplands of Heilongjiang Province in northeast China. Three counties (Lindian, Hailun and Baoqing) were selected as typical croplands representing major soil types and land use types in the region. RESULTS: The changes in SOC density (SOCD) between 1981 and 2001 were -6.6, -14.7 and 5.7 Mg C ha(-1) in Lindian, Hailun and Baoqing Counties respectively. The total SOC storage (SOCS) changes were estimated to be -11.3, -19.1 and 16.5% of those in 1981 in the respective counties. The results showed 22-550% increases in SOCS in rice (Oryza sativa L.) paddies in the three counties, but 28-33% decreases in dry cropland in Lindian and Hailun Counties. In addition, an increase of 11.4 Mg C ha(-1) in SOCD was observed in state-owned farms (P < 0.05), whereas no significant change was observed in family-owned farms. CONCLUSION: Soil C:N ratio and initial SOCD related to soil groups were important determinants of SOCD changes. Land use and residue returning greatly affected SOC changes in the study region. To increase the topsoil SOCD, the results suggest the conversion of dry croplands to rice paddies and returning of crop residue to soils.

Genetic polymorphism of pharmacogenomic VIP variants in the Deng people from the Himalayas in Southeast Tibet.

Little is known about polymorphic distribution of pharmacogenes among ethnicities, including the Deng people. In this study, we recruited 100 unrelated, healthy Deng people and genotyped them with respect to 76 different single-nucleotide polymorphisms by the PharmGKB database. Our results first indicated that the polymorphic distribution of pharmacogenes of the Deng people is most similar to CHD, suggesting that Deng people have a closest genetic relationship with CHD. Our data will enrich the database of pharmacogenomics and provide a theoretical basis for safer drug administration and individualized treatment plans, promoting the development of personalized medicine.

Analysis of difference of association between polymorphisms in the XRCC5, RPA3 and RTEL1 genes and glioma, astrocytoma and glioblastoma.

BACKGROUND: Gliomas are the most common aggressive brain tumors and have many complex pathological types. Previous reports have discovered that genetic mutations are associated with the risk of glioma. However, it is unclear whether uniform genetic mutations exist difference between glioma and its two pathological types in the Han Chinese population. MATERIALS AND METHODS: We evaluated 20 SNPs of 703 glioma cases (338 astrocytoma cases, 122 glioblastoma cases) and 635 controls in a Han Chinese population using χ(2) test and genetic model analysis. RESULTS: In three case-control studies, we found rs9288516 in XRCC5 gene showed a decreased risk of glioma (OR, 0.85; 95% CI, 0.73-0.99; P = 0.042) and glioblastoma (OR, 0.70; 95% CI, 0.52-0.92; P = 0.001) in the allele model. We identified rs414805 in RPA3 gene showed an increased risk of glioblastoma in allele model (OR, 1.38; 95% CI, 1.00-1.89; P = 0.047) and dominant model (OR, 1.57; 95% CI, 1.05-2.35; P = 0.027), analysis respectively. Meanwhile, rs2297440 in RTEL1 gene showed an increased risk of glioma (OR, 1.30; 95% CI, 1.10-1.54; P = 0.002) and astrocytoma (OR, 1.26; 95% CI, 1.02-1.54; P = 0.029) in the allele model. In addition, we also observed a haplotype of "GCT" in the RTEL1 gene with an increased risk of astrocytoma (P = 0.005). CONCLUSIONS: Polymorphisms in the XRCC5, RPA3 and RTEL1 genes, combinating with previous reaserches, are associated with glioma developing. However, those genes mutations may play different roles in the glioma, astrocytoma and glioblastoma, respectively.

Genetic polymorphism of pharmacogenomic VIP variants in the Deng people from the Himalayas in Southeast Tibet.

Little is known about polymorphic distribution of pharmacogenes among ethnicities, including the Deng people. In this study, we recruited 100 unrelated, healthy Deng people and genotyped them with respect to 76 different single-nucleotide polymorphisms by the PharmGKB database. Our results first indicated that the polymorphic distribution of pharmacogenes of the Deng people is most similar to CHD, suggesting that Deng people have a closest genetic relationship with CHD. Our data will enrich the database of pharmacogenomics and provide a theoretical basis for safer drug administration and individualized treatment plans, promoting the development of personalized medicine.

Association between RTEL1, PHLDB1, and TREH Polymorphisms and Glioblastoma Risk: A Case-Control Study.

BACKGROUND: Glioblastoma (GBM) is a highly invasive, aggressive, and incurable brain tumor. Genetic factors play important roles in GBM risk. The aim of this study was to elucidate the influence of gene polymorphism on GBM susceptibility. MATERIAL AND METHODS: In this case-control study, we included 72 GBM patients and 320 healthy controls to analyze the association between 29 single-nucleotide polymorphisms and GBM cancer risk in the Chinese Han population. The single-nucleotide polymorphisms were determined by Sequenom MassARRAY RS1000 and statistical analysis was performed using SPSS software and SNPStats software. RESULTS: Using the χ(2) test, we found that rs2297440 and rs6010620 in RTEL1 increased risk of GBM. In the recessive model, we also found that the genotypes "CC" of rs2297440 and "GG" of rs6010620 in RTEL1 significantly increased GBM risk. The variant TT genotype of TREH rs17748 and the variant TT genotype of PHLDB1 rs498872 decreased GBM risk in the recessive model. We also found that the TREH rs17748 variant C allele showed an increased risk in males in the dominant model. CONCLUSIONS: Our results suggest a significant association between the RETL1, TREH, and PHLDB1 genes and GBM development in the Han Chinese population.

Genetic polymorphisms of pharmacogenomic VIP variants in the Uygur population from northwestern China.

BACKGROUND: Drug response variability observed amongst patients is caused by the interaction of both genetic and non-genetic factors, and frequencies of functional genetic variants are known to vary amongst populations. Pharmacogenomic research has the potential to help with individualized treatments. We have not found any pharmacogenomics information regarding Uygur ethnic group in northwest China. In the present study, we genotyped 85 very important pharmacogenetic (VIP) variants (selected from the PharmGKB database) in the Uygur population and compared our data with other eleven populations from the HapMap data set. RESULTS: Through statistical analysis, we found that CYP3A5 rs776746, VKORC1 rs9934438, and VKORC1 rs7294 were most different in Uygur compared with most of the eleven populations from the HapMap data set. Compared with East Asia populations, allele A of rs776746 is less frequent and allele A of rs7294 is more frequent in the Uygur population. The analysis of F-statistics (Fst) and population structure shows that the genetic background of Uygur is relatively close to that of MEX. CONCLUSIONS: Our results show significant differences amongst Chinese populations that will help clinicians triage patients for better individualized treatments.

The association between phospholipase C epsilon gene (PLCE1) polymorphisms and colorectal cancer risk in a Chinese Han population: a case-control study.

BACKGROUND: Heritable factors contribute to the development of colorectal cancer (CRC). We investigated the association between single nucleotide polymorphisms in phospholipase C epsilon 1 (PLCE1) and CRC susceptibility. METHODS: We selected eight tag single nucleotide polymorphisms (tSNPs) and investigated whether they were associated with CRC in Chinese Han population. In this study, we used Sequenom MassARRAY technology and genotyped 276 CRC cases and 385 controls. The effects of the polymorphisms on the risk of CRC were expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs), evaluated by different genetic models using unconditional logistic regression analysis adjusted for age and gender. We also analyzed the risk of the eight PLCE1 tSNPs in different histology of CRC. RESULTS: Based on x(2) tests, rs753724 (OR = 1.49, 95% CI: 1.10-2.03, P = 0.010) and rs10882424 (OR = 1.32, 95% CI: 1.02-1.70, P = 0.037) in PLCE1 were associated with CRC. In genetic model analyses, we found that rs753724 in PLCE1 may increase CRC risk (OR = 1.48, 95% CI: 1.09-2.03, P = 0.013) in the log-additive model, and rs11187842 in PLCE1 may increase CRC risk (OR = 3.09, 95% CI: 1.17-8.14, P = 0.018) in the recessive model. Rs753724 TT (OR = 4.31, P = 0.010), rs11187842 TT (OR = 5.78, P = 0.003), and rs10882424 GG (OR = 2.64, P = 0.022) in PLCE1 may increase rectal cancer in a recessive model. CONCLUSIONS: Our results suggest that PLCE1 may be associated with CRC in Han Chinese population.