KDR rs1870377基因与经皮冠状动脉介入治疗术后氯吡格雷耐药相关性分析

摘要 目的：探讨与分析KDR rs1870377基因与经皮冠状动脉介入治疗（percutaneous coronary intervention, PCI）术后氯吡格雷耐药相关性。方法：2018年5月到2021年2月选在航天中心医院（北京大学航天临床医学院）老年医学一科住院的冠心病患者97例作为研究对象,所有患者在PCI术后判定氯吡格雷耐药情况,检测KDR rs1870377基因多态性状况并进行相关性分析。结果：在97例患者中,PCI术后氯吡格雷耐药22例(耐药组),耐药率为22.7 %。耐药组的空腹血糖、总胆固醇、甘油三酯等与非耐药组对比差异无统计学意义（P>0.05）。KDR rs1870377基因主要包括AA、CC、CA三种基因型,两组都与Hardy-Weinberg平衡定律相符合,研究对象具有群体代表性。耐药组的KDR rs1870377基因CC基因型高于非耐药组（P<0.05）,耐药组的等位基因C频率高于非耐药组（P<0.05）。Spearsman分析显示KDR rs1870377基因CC基因型、等位基因C与氯吡格雷耐药存在相关性（P<0.05）。多元Logistic回归分析显示KDR rs1870377基因CC基因型、等位基因C为导致PCI术后氯吡格雷耐药的重要因素（P<0.05）。结论：冠心病患者PCI术后氯吡格雷比较常见,也伴随有KDR rs1870377基因多态性,KDR rs1870377基因CC基因型、等位基因C为导致PCI术后氯吡格雷耐药的重要因素。     

Serotonergic genes modulate amygdala activity in major depression

Serotonergic genes have been implicated in the pathogenesis of depression probably via their influence on neural activity during emotion processing. This study used an imaging genomics approach to investigate amygdala activity in major depression as a function of common functional polymorphisms in the serotonin transporter gene (5-HTTLPR) and the serotonin receptor 1A gene (5-HT(1A)-1019C/G). In 27 medicated patients with major depression, amygdala responses to happy, sad and angry faces were assessed using functional magnetic resonance imaging at 3 Tesla. Patients were genotyped for the 5-HT(1A)-1019C/G and the 5-HTTLPR polymorphism, including the newly described 5-HTT-rs25531 single nucleotide polymorphism. Risk allele carriers for either gene showed significantly increased bilateral amygdala activation in response to emotional stimuli, implicating an additive effect of both genotypes. Our data suggest that the genetic susceptibility for major depression might be transported via dysfunctional neural activity in brain regions critical for emotion processing.     

Association between the rs3751143 polymorphism of P2RX7 gene and chronic lymphocytic leukemia: A meta-analysis

Purinergic Signalling - Meta-analysis was used to determine the association between rs3751143 polymorphism of P2RX7 gene and the risk of chronic lymphocytic leukemia (CLL). Search for published...     

A SNP of miR‐146a is involved in bladder cancer relapse by affecting the function of bladder cancer stem cells via the miR‐146a signallings

MiR‐146a‐5p in urine samples was recently reported to be possibly used as a prognostic marker for bladder cancer (BC). Interestingly, YAP1 and COX2 were both demonstrated to function as stem cell regulators in BC. Therefore, in this study, we aimed to establish the molecular mechanism underlying the role of miR‐146a, YAP1 and COX2 in BC relapse. We also studied the possibility of using the C > G genotype of miR‐146a rs2910164 SNP as an indicator of BC relapse. A total of 170 BC patients were assigned into different groups based on their genotypes of rs2910164 SNP. Kaplan‐Meier survival curves were plotted to compare the recurrence‐free rate among these groups. Real‐time PCR, Western Blot, bioinformatic analysis, luciferase assay and IHC assay were conducted to study the role of rs2910164 SNP in the progression of BC. Accordingly, GC/CC‐genotyped patients presented a higher risk of recurrence when compared with GG‐genotyped patients, while the expression of BC regulators was influenced by the presence of rs2910164. COX2 mRNA and YAP1 mRNA were, respectively, validated as direct target genes of miR‐146a, and the expression of YAP1 and COX2 mRNA/protein was both suppressed by miR‐146a precursors. The expression of ALDH1A1 mRNA/protein was inhibited upon the down‐regulation of YAP1, while the expression of let7 and SOX2 mRNA/protein was inhibited upon the down‐regulation of COX2. In conclusion, two signalling pathways, miR‐146a/YAP1/ALDH1A1 and miR‐146a/COX2/PGE2/let7/SOX2, were modulated by miR‐146a. As an SNP regulating the expression of miR‐146a, the rs2910164 G > C SNP could be utilized as a biomarker for BC relapse.     

TNRC9基因rs12443621A/G多态性与中国女性乳腺癌易感性及临床病理关系的研究

目的：研究TNRC9/LOC643714基因rs12443621A/G多态性与乳腺癌易感性及临床病理之间的关系。方法：DNA试剂盒提取321例乳腺癌患者和340例正常女性静脉血全基因组DNA,PCR扩增目的基因片段,提取扩增样本进行DNA测序检测分析rs12443621多态性。应用SPSS17.0软件对实验结果进行统计学分析。结果：应用SPSS17.0软件对TNRC9/LOC643714基因rs12443621A/G多态性AA、AG、GG进行卡方检验分析,结果显示三种基因型分布在病例组及对照组中无统计学意义（X2=1.43,P〉0.05）,与乳腺癌易感性无关,与乳腺癌病理分型、ER、PR、HER-2状态以及淋巴结是否转移无相关性（X2=2.90,P〉0.05;X2=2.25,P〉0.05;X2=1.671,P〉0.05;X2=1.34,P〉0.05;X2=3.24,P〉0.05）。结论：TNRC9基因rs12443621A/G多态性与乳腺癌易感性及临床病理特征无关,不能作为独立的基因标志物对乳腺癌进行早期检测和诊断。     

The interaction of the Chrna5 D398N variant with developmental nicotine exposure

A single nucleotide polymorphism (SNP) in CHRNA5 (rs16969968, change from an aspartic acid [D] to asparagine [N] at position 398 of the human α5 nicotinic acetylcholine receptor subunit) has been associated with increased risk for nicotine dependence. Consequently, carriers of the risk variant may be at elevated risk for in utero nicotine exposure. To assess whether this gene‐environment interaction might impact nicotine intake in developmental nicotine‐exposed offspring, we utilized a mouse expressing this human SNP. D and N dams drank nicotine (100 μg/mL) in 0.2% saccharin water or 0.2% saccharin water alone (vehicle) as their sole source of fluid from 30 days prior to breeding until weaning of offspring. The nicotine (D Nic, N Nic) or vehicle (D Veh, N Veh) exposed offspring underwent a 2‐bottle choice test between postnatal ages of 30 to 46 days. N Nic offspring consumed the most nicotine at the highest concentration (400 μg/mL) compared with all other groups. In contrast, D Nic offspring drank the least amount of nicotine at all concentrations tested. Nicotine‐stimulated dopamine (DA) release measured from striatal synaptosomes was increased in D Nic offspring, while decreased in N Nic offspring relative to their genotype‐matched controls. These data suggest that the α5 variant influences the effect of developmental nicotine exposure on nicotine intake of exposed offspring. This gene‐environment interaction on striatal DA release may provide motivation for increased nicotine seeking in N Nic offspring and reduced consumption in D Nic offspring.     

Association of single nucleotide polymorphism rs2065955 of the <Emphasis Type="Italic">filaggrin</Emphasis> gene with susceptibility to Epstein-Barr virus-associated gastric carcinoma and EBV-negative gastric carcinoma

The relationship between the Filaggrin gene (FLG) rs2065955 polymorphism and susceptibility to Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC) was investigated in Shandong Province, China. We detected the FLG rs2065955 genotype and allele distribution by using PCR and restriction fragment length polymorphism (RFLP) in 64 EBVaGC, 82 EBVnGC, and 111 normal control samples. Immunohistochemistry was used to detect the level of FLG protein in 35 EBVaGC and 51 EBVnGC tumor tissues. Compared with normal controls, the genotype CC and allele C of FLG rs2065955 showed higher frequency in EBVaGC and EBVnGC. There was no significant difference between EBVaGC and EBVnGC in allele distribution of FLG rs2065955, but the genotype CC was found more frequently in EBVaGC than in EBVnGC. The risk of developing either EBVaGC or EBVnGC in genotype CC was higher than in other genotypes. Furthermore, genotype CC of FLG rs2065955 may contribute more to the risk of developing EBVaGC than EBVnGC. There was no significant difference in the expression level of FLG protein between EBVaGC and EBVnGC. In conclusion, the FLG rs2065955 polymorphism was significantly related to gastric carcinoma. Allele C of FLG rs2065955 could be a risk factor for EBVaGC or EBVnGC, while genotype CC of FLG rs2065955 was especially associated with EBVaGC.

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