Genetic polymorphisms of the drug-metabolizing enzyme CYP2C19 in the Uyghur population in northwest China

1.?CYP2C19 is a clinically important enzyme and is involved in the metabolism of approximately 10% of drugs used in daily clinical practice. Previous studies mainly focused on Chinese Han populations or other ethnic groups, little is known about Uyghur populations.

2.?The present study was designed to determine the genetic basis of CYP2C19 polymorphisms.

3.?We used direct sequencing to investigate the promoter, exons and surrounding introns, and 3′-untranslated region of the CYP2C19 gene in 96 unrelated healthy Uyghur individuals.

4.?A total of 31 different CYP2C19 polymorphisms were identified in the Uyghur population, three of which were novel, including two nonsynonymous variants (57807A?>?M, Gln279Pro and 19257G?>?R, Asp262Asn) and one synonymous variants in exon 5 (19184T?>?Y, Leu237Leu). In addition, CYP2C19*1, *2 and *3 alleles showed frequencies of 83.34%, 14.06% and 2.08%, respectively.

5.?This is the first study that systematically screened the polymorphisms of the whole CYP2C19 gene in Uyghur population. Hence, our results provided important information on CYP2C19 polymorphisms in Uyghur population and could be helpful for future personalized medicine studies in Uyghur population generally.     

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

1. 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.

2. 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.

3. 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.

4. 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.

     

Impact of multiple Alcohol Dehydrogenase gene polymorphisms on risk of laryngeal,esophageal, gastric and colorectal cancers in Chinese Han population

Alcohol intake is positively associated with the risk of upper aerodigestive tract (UADT) cancers; but its effect on gastric or colorectal cancer is controversial. Previous study had identified several single nucleotide polymorphisms (SNPs) of Alcohol Dehydrogenase (ADH) genes associated with UADT cancers in European and Japanese populations. We sought to determine if these SNPs associated with laryngeal, esophageal, gastric or colorectal cancer in Chinese population. We conducted a case-control study among 1577 cases and 1013 healthy controls from northwest China. Five SNPs associated with UADT cancers risk were selected from previous genome-wide association studies and genotyped using Sequenom Mass-ARRAY technology. Odds ratios and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for age and gender. We identified that the minor alleles of rs1789924 and rs971074 were associated with decreased risk of laryngeal cancer (OR = 0.311; 95% CI = 0.161-0.602; P < 0.001) and esophagus cancer (OR = 0.711; 95% CI = 0.526-0.962; P = 0.027) in allelic model analysis, respectively. In the genetic model analysis, we found the “C/T” genotype of rs1789924 was associated with decreased laryngeal cancer risk in codominant model (P = 0.046) and overdominant model (P = 0.013); the “C/T-T/T” genotype of rs1789924 was associated with reduced risk of laryngeal cancer under dominant model (P = 0.013). Additionally, none of the SNPs was associated with gastric or colorectal cancer in our study. Our data shed new light on the association between ADH SNPs and respiratory and digestive tract cancers susceptibility in the Han Chinese population.     

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 χ² 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.     

去白细胞悬浮红细胞制剂储存过程中活性氧族及丙二醛含量变化

目的 探讨去白细胞悬浮红细胞制剂储存过程中活性氧族(ROS)含量及丙二醛(MDA)含量的变化.方法 从2013年5～6月于河北省血液中心制备的去白细胞悬浮红细胞制剂中,采用简单随机抽样方法抽取6份去白细胞悬浮红细胞制剂标本作为研究对象.于储存后第0,7,14,28,42天,采用荧光探针2',7'-二氧荧光黄双乙酸盐(DCFH-DA)孵育的方法观察去白细胞悬浮红细胞荧光强度,并对去白细胞悬浮红细胞制剂内ROS含量与MDA含量进行检测.对储存后去白细胞悬浮红细胞制剂内ROS含量、MDA含量分别与储存时间进行相关性分析;并对储存后去白细胞悬浮红细胞制剂内ROS含量与MDA含量进行相关性分析.结果 ①随着储存时间的延长,经荧光探针DCFH-DA孵育的去白细胞悬浮红细胞的荧光强度显著增强;②储存后第0,7,14,28,42天去白细胞悬浮红细胞制剂内ROS含量呈显著增高趋势,第42天去白细胞悬浮红细胞内ROS含量显著高于第0,7,14,28天ROS含量,并且差异均有统计学意义(P＜0.01,0.05,0.05,0.05);且去白细胞悬浮红细胞制剂内ROS含量与储存时间呈正相关关系(r=0.898,P＜0.01);③储存后第0,7,14,28,42天去白细胞悬浮红细胞内MDA含量呈显著增高趋势,第42天去白细胞悬浮红细胞内MDA含量显著高于第0,7,14,28天MDA含量,并且差异均有统计学意义(P＜0.01,0.01,0.01,0.05);且去白细胞悬浮红细胞内MDA含量与储存时间呈正相关关系(r=0.930,P＜0.01);④储存后第0,7,14,28,42天,去白细胞悬浮红细胞制剂内ROS含量均分别与对应时间点MDA含量呈正相关关系(r=0.877,0.872,0.823,0.786,0.907;P＜0.05).去白细胞悬浮红细胞制剂储存后第0,7,14,28,42天,各时间点ROS含量均值与MDA含量均值亦呈正相关性关系(r=0.981,P＜0.01).结论 去白细胞悬浮红细胞制剂储存过程中ROS含量与MDA含量均显著增高,红细胞内氧化应激反应增强,其为导致去白细胞悬浮红细胞制剂储存损伤的重要原因.     

床旁超声对社区获得性肺炎老年患者的诊断价值

目的探讨床旁超声检查对于诊断社区获得性肺炎老年患者的诊断价值。方法选取本院2019年8月~2020年6月收治的120例社区获得性肺炎老年患者作为感染组、60例健康志愿者作为对照组,两组分别接受床旁超声的检查,对比两组的肺部超声征象（A线征象、B线征象、肺实变征象）及肺部超声评分,并根据患者病情程度进行分层对比,采用ROC曲线分析肺部超声评分诊断肺部感染的价值。结果感染组的A线征象、B线征象、肺实变征象检出率及肺部超声评分均高于对照组,差异具有统计学意义（P < 0.05）. CPIS评分>6分的感染组患者的肺实变征象检出率及肺部超声评分均高于CPIS评分≤6分的患者,差异具有统计学意义（P < 0.05）;CPIS评分>6分的感染组患者的A线征象、B线征象与CPIS评分≤6分的患者比较,差异无统计学意义（P> 0.05）;死亡组患者的B线征象、肺实变征象检出率及肺部超声评分均高于存活患者,差异具有统计学意义（P < 0.05）;肺部超声评分诊断肺部感染的敏感度为89.87%,特异性为83.36%,漏诊率为10.13%,误诊率为16.64%,ROC曲线下面积值为0.913。结论床旁超声检查对于诊断社区获得性肺炎老年患者及病情判断均具有较高的临床价值。      

Quasi‐average mean square consensus for wireless sensor networks under three topologies with respect to sleeping‐awaking method

The quasi‐average mean square consensus problem for wireless sensor networks is studied in this paper. The related networks considered are time continuous and linear, and possess the leader–follower structures in which some sensors act as leaders and the others act as followers, with the locale information controlled. Three different leader–follower structures are proposed in this paper. The first one is the topology with fixed leaders and varying followers which arrives at a quasi‐average mean square consensus by applying the sleeping‐awaking method to all cliques of the followers. The second one is the topology with fixed leaders and fixed followers which arrives at a quasi‐average value consensus via the general protocol. The third one is the topology with varying leaders and fixed followers which arrives at a quasi‐average mean square consensus by applying the sleeping‐awaking method to all cliques of the leaders. For mentioned three topologies, some necessity and sufficiency conditions of the related consensus are obtained, respectively. To illustrate the effectiveness of the obtained results, some numerical examples are presented finally. Copyright © 2012 John Wiley & Sons, Ltd.     

CLPTM1L Genetic Polymorphisms and Interaction With Smoking and Alcohol Drinking in Lung Cancer Risk: A Case–Control Study in the Han Population From Northwest China

Genetic variants of cleft lip and palate trans-membrane 1-like (CLPTM1L) genes in the p15.33 region of chromosome 5 were previously identified to influence susceptibility to lung cancer. We examined the association of single nucleotide polymorphisms (SNPs) in CLPTM1L genes with lung cancer and explored their potential effects on the relationship between environmental risk factors (smoking, drinking) and lung cancer in a Chinese Han population.We genotyped 9 single nucleotide polymorphisms (SNPs) of CLPTM1L in a case–control study with 228 lung cancer cases and 301 controls from northwest China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression.We identified that the minor alleles of rs451360, rs402710, and rs31484 in CLPTM1L were associated with a 0.52-fold, 0.76-fold, and 0.70-fold decreased risk of lung cancer in allelic model analysis, respectively. In the genetic model analysis, we found rs402710 and rs401681 were associated with decreased lung cancer risk. Further stratification analysis showed that rs380286 displayed a significantly decreased lung cancer risk (OR = 0.65, P = 0.041) in the non-drinkers. In addition, Haplotype “GTTATCTGT” was found to be associated with decreased lung cancer risk (OR = 0.50, P = 0.033).Our results verified that genetic variants of CLPTM1L contribute to lung cancer susceptibility in the northwest Chinese Han population. Additionally, we found that consumption of alcohol may interact with CLPTM1L polymorphisms to contribute to overall lung cancer susceptibility.