SNP Identification in α_(2A)-Adrenergic Receptor Gene in Chinese and the Effect on Gene Expression

Objective: To scan single nucleotide polymorphism ( SNP ) in Chinese alpha-2Aadrenergic receptor (α_(2A)-AR) gene and study the effects of the SNP on the gene expression.Methods: The complete sequence of α_(2A)-AR gene was analyzed with automated DNA sequencer to scanSNPs. Genomic DNA was extracted from whole blood and a 239 bp fragment containing the G/Cpolymorphism was amplified with PCR using a pair of. specific primers. PCR-RFLP was used to performthe genotyping of the SNP at the site-1 296 bp of the people in the North of China. Electrophoresismobility shift assay ( EMSA ) was used to study the binding of the 390 bp fragments (- 1 414-1 025bp) with G or C at the site-1 296 bp and nuclear extracts . Results: In our study, two SNPs werefound in α_(2A)-AR gene. Allele frequencies of the SNP at the site-1 296 bp were 0.61 and 0.39 forG and C , and the genotype frequencies were 0.34 , 0.54 and 0.13 for GG, GC and CC respectively fromthe people in the North of China. In the EMSA, a specific binding appeared in the complex ofnuclear extracts and DNA with C at-1 296 bp . Conclusion: Two SNPs exist in α_(2A)-AR gene from thepeople in the North of China , and DNA fragment with allele C of the SNP at the site-1 296 bp couldbind with a specific protein, which could influence the gene expression.

Genetic variations of beta 2-adrenergic receptor gene are associated with essential hypertension in Xinjiang Kazakans

Objective The aims of the present study were to investigate the associations of 46 A〉G, 79 C〉G, 491 C〉T and 659 C〉G genetic variants of the human beta 2-adrenergic receptor （β2-AR）, ADRB2, gene with essential hypertension （EH） in Xinjiang Kazakans population.Methods A gender-matched case-control （271 hypertensive cases and 267 normotensive controls） study was used to investigate the associations of the four variations in the coding region of ADRB2 with EH. The genotypes of the variants were identified by the polymerase chain reaction and restriction fragment length polymorphism （PCR-RFLP） methods. Results 46 A〉G, 79 C〉G and 659 C〉G polymorphisms were common in the Kazakan population, but 491 C〉T was a mutation （frequency ofT allele was only 0.003） and only found in EH group. The fxequency distributions of genotypes and alleles for 659 C〉G between the EH and control groups was significantly different （P〈0.05）, while those for 46 A〉G and 79 C〉G polymorphisms were not statistically different. Logistic regression analysis suggested that the G allele of 659 C〉G polymorphism was a risk factor for hypertension （minor allele vs common homo; odds ratio, 13.240, 95% CI, 4.052-43.274; P〈0.05）. Covariance analysis showed that systolic and diastolic blood pressure levels in GG＋CG group of 659 C〉G were significantly higher than those in the CC group, but no significant difference of blood pressure were found between common homo and minor allele for 46 A〉G and 79C〉G polymorphisms. Haplotype analysis showed that two hyplotypes, HI： 46A-79C-491C-523C（48%）and H5：46A-79C-491C-659G, were associated with EH.Conelusion ADRB2 genetic variants may play independent roles in the molecular genetic mechanism of EH in Xinjiang Kazakans population （d Geriatr Cardio12010; 7：52-57）.

Activation of β_2-Adrenergic Receptor Induced by Three Catecholamine Agonists:a Docking and Molecular Dynamics Study

We studied the activation of β2-adrenergic receptor（β2AR） by norepinephrine, epinephrine and isoprote- renol using docking and molecular dynamics（MD） simulation. The simulation was done on the assumption that β2AR was surrounded with explicit water and infinite lipid bilayer membrane at body temperature. So the result should be close to that under the physiological conditions. We calculated the structure of binding sites in β2AR for the three ac- tivators. We also simulated the change of the conformation ofβ2AR in the transmembrane regions（TMs）, in the mo- lecular switches, and in the conserved DRY（Aspartic acid, Arginine and Tyrosine） motif. This study provides detailed information concerning the structure ofβ2AR during activation process.

Effects ofβ_2-Adrenergic Antagonist on Cytosolic Ca^(2+) in Ventricular Myocytes from Infarcted Rat Heart

Objectives To investigate the effects of β2-adrenergic antagonist on cytosolic Ca^2 ＋ （[Ca^2＋ ]i） in ventricular myocytes from infarcted rat heart. Methods A ligature was placed around left anterior descending coronary artery of rat hearts. Rats in the control group were sham-operated. Cardiomyocytes were dissociated at two, four, eight weeks after myocardial infarction （MI） and [Ca^2＋]i was measured via fura-2 fluorescence. The response of cardiomyocytes to isoproterenol in presence or absence of betal-adrenergic antagonist atenolol, beta2-adrenergic antagonist ICI118, 551 or non-selective β1, 2- adrenergic antagonists propranolol was examined. Results The followings were found that ICI 118, 551 had no significant effects on the rise of [Ca^2＋]i induced by isoproterenol in normal ventricular myocytes （P 〉 0.05）, ICI118, 551 only significantly attenuated the rise of [Ca^2＋]i induced by isoproterenol at four weeks and eight weeks after MI （24.5%±5.7% vs 57.8% ± 13.2%, P〈 0.01; 12.2%±7.9% vs 44.6%±11.3%, P〈 0.01）. Atenolol had suppressive effects only in the control group and the post-MI group of two weeks （P 〈 0.05）, and propranolol had suppressive effects in the control and all the three post-MI groups （P 〈 0.01）. Conclusions Beta2-adrenergic antagonist ICI118, 551 may exert negative effects on Ca^2＋ overload initiated by sympathetic stimulation after MI.

Beta-adrenergic receptor polymorphisms: A basis for pharmacogenetics

Aims: Polymorphisms of the β-adrenergic receptor, the frequency of which may differ in ethnic groups, alters β-receptor function. The aim of this study was to elucidate the frequency of β1 and β2-adrenergic receptor polymorphisms in healthy Greeks and to compare with those of Caucasian European (Euro) and African American (AA) origin. Methods: Ninety-nine individuals with a median age of 63 without clinical evidence of any disease were studied. Blood samples were obtained and common β1 and β2-adrenergic receptor polymorphisms that change the en-coded amino acid were determined by pyrosequencing. Results: The most common β1-adrenergic receptor polymorphism in Greeks is nucleotide substitution cytosine for guanine at position 1165 (1165 C/G) resulting in amino acid substitution arginine for glycine at position 389 (389 Arg/Gly) with a minor allele frequency of 28% (Euro 27%, AA 42%);this polymorphism increases the sensitivity of the β1-receptor. The most common β2-adrenergic receptor polymorphism in Greeks is the nucleotide substitution guanine for adenine at position 46 (46 G/A) resulting in amino acid substitution glycine for arginine at position 16 (16 Gly/Arg) with a minor allele frequency of 38% (Euro 41%, AA 50%);this polymerphism facilitates receptor down-regulation during chronic adrenergic stimulation. Conclusion: The most common β1 and β2-adrenergic receptor polymorphisms in the Greek population are similar to those of other European ancestry, and less common than in those of African origin indicating variability in ethnic groups. This information provides insight into common polymorphisms that may assist in optimizing β-antagonist and agonist therapy.

Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease

AIM： To evaluate the role of genetic factors in the pathogenesis of Crohn＇s disease （CD） and ulcerative colitis （UC）, we investigated the single nucleotide polymorphisms （SNPs） of NOD2/CARD15 （R702W, Gg08R and L1007finsC）, and Toll-like receptor 4 （TLR4） genes （D299G and T399I） in a selected inflammatory bowel disease （IBD） population coming from Southern Italy. METHODS： Allele and genotype frequencies of NOD2/ CARD15 （R702W, Gg08R and L1007finsC） and TLR4 （D299G and T399I） SNPs were examined in 133 CD patients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed. RESULTS： NOD2/CARD15 R702W mutation was significantly more frequent in CD （9.8%） than in controls （2.4%, P = 0.001） and in UC （2.3%, P = 0.03）. No significant difference was found between UC patients and control group （P 〉 0.05）. In CD and UC patients, no significant association with G908R variant was found. L1007finsC SNP showed an association with CD （9.8%） compared with controls （2.9%, P = 0.002） and UC patients （2.3%, P = 0.01）. Moreover, in CD patients, G908R and L1007finsC mutations were significantly associated with different phenotypes compared to CD wild-type patients. No association of IBD with the TLR4 SNPs was found in either cohort （allele frequencies： D299G-controls 3.9%, CD 3.7%, UC 3.4%, P 〉 0.05; T399I-controls 2.9%, CD 3.0%, UC 3.4%, P 〉 0.05）. CONCLUSION： These findings confirm that, in our IBD patients selected from Southern Italy, the NOD2/ CARD15, but not TLR4 SNPs, are associated with increased risk of CD.

β-2 Adrenergic receptor gene polymorphism and response to propranolol in cirrhosis

AIM: To evaluate the association of β-2 adrenergic receptor(β2-AR) gene polymorphism with response of variceal pressure to propranolol in cirrhosis.METHODS: Sixty-four non-related cirrhotic patients participated in this study and accepted variceal pressure measurement before and after propranolol administration. Polymorphism of the β 2-AR gene was determined by directly sequencing of the polymerase chain reaction products from the DNA samples that were prepared from the patients.RESULTS: The prevalence of Gly16-Glu/Gln27 and Arg16-Gln27 homozygotes, and compound heterozygotes was 29.7%, 10.9%, and 59.4%, respectively.Patients with cirrhosis with Gly16-Glu/Gln27 homozygotes had a greater decrease of variceal pressure after propranolol administration than those with Arg16-Gln27 homozygotes or with compound heterozygotes(22.4% ± 2.1%, 13.1% ± 2.7% and 12.5% ± 3.1%,respectively, P < 0.01).CONCLUSION: The variceal pressure response to propranolol was associated with polymorphism of β 2-AR gene. Patients with the Gly16-Glu/Gln27 homozygotes probably benefit from propranolol therapy.

The 5-HT2c receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

It has been postulated that the persistent short intravaginal ejaculation latency time （IELT） of men with lifelong premature ejaculation （LPE） is related to 5-hydroxytryptamine （HT）2c receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2c receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2c receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2c receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were.investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2c receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes （Cys/Cys） is significantly lower （22.6s; 95% CI 18.3-27.8s） than in male homozygous mutants （Ser/Ser） （40.4s; 95% CI 20.3-80.4s） （P = 0.03）. It is concluded that Cys23Ser 5-HT2c receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.

Effect of Dai-Saiko-To (Da-Chai-Hu-Tang) on LDL-Receptor Gene Expression in Human Hepatoma Cell Line (HepG2)

We previously reported that Dai-saiko-to (Da-Chai-Hu-Tang), a traditional Japanese kampo medicine, increased LDL receptor mRNA expression in the liver of the hypercholesterolemic rabbits. In this study, we focused on LDL receptor gene expression in a human hepatoma cell line (HepG2) treated with Dai-saiko-to extract and the extracts of eight herbs presented in Dai-saiko-to. Dai-saiko-to extract significantly increased LDL receptor gene and SREBP2 gene expression compared with the control. The extracts of four herbs, Bupleurum root, Pinellia tuber, Scutellaria root and Peony root significantly increased the LDL receptor gene expression. Whereas, Jujube, Immature orange, Ginger and Rhubarb extracts did not change the gene expression. These results suggest that Dai-saiko-to increased the expression of the cholesterol transport gene (LDL receptor) regulated by SREBP2 gene in the human hepatoma cell line. The pharmacological activity of Dai-saiko-to against hypercholesterolemia and atheromatous lesions related for these four herbal components.

The human δ2 glutamate receptor gene is not mutated in patients with spinocerebellar ataxia

The human glutamate receptor delta 2 gene （GRID2） shares 90%homology with the orthologous mouse gene. The mouse Grid2 gene is involved with functions of the cerebellum and sponta-neous mutation of Grid2 leads to a spinocerebellar ataxia-like phenotype. To investigate whether such mutations occur in humans, we screened for mutations in the coding sequence of GRID2 in 24 patients with familial or sporadic spinocerebellar ataxia and in 52 normal controls. We de-tected no point mutations or insertion/deletion mutations in the 16 exons of GRID2. However, a polymorphic 4 nucleotide deletion （IVS5-121_-118 GAGT） and two single nucleotide polymor-phisms （c.1251G〉T and IVS14-63C〉G） were identiifed. The frequency of these polymorphisms was similar between spinocerebellar ataxia patients and normal controls. These data indicate that spontaneous mutations do not occur in GRID2 and that the incidence of spinocerebellar ataxia in humans is not associated with GRID2 mutation or polymorphisms.

β_2肾上腺素受体基因多态性和支气管哮喘的关系

目的探讨β2肾上腺素受体(β2-adenergicreceptor,β2AR)基因多态性与我国北方汉族支气管哮喘遗传易感性及与哮喘临床表型间的关系。方法采用聚合酶链反应(PCR)—限制性内切酶片段长度多态性(RFLP)和等位基因特异性PCR(ASP)检测16、27、164位β2AR基因多态性在125名哮喘患者和96名健康对照者间的分布;并测定哮喘患者血清的TIgE、肺通气功能(FEV1,FEV1%,FEV1/FVC)、支气管舒张试验、乙酰甲胆碱(Mch)气道激发试验(如果FEV1%>70%)。结果Gly16纯合基因型在哮喘组的频率较健康对照组的频率明显升高(22.4%vs8.3%,P<0.05),优势比(OR)为2.918(95%CI:1.256～6.781);等位基因Gly16的频率在哮喘组明显高于健康对照组(0.26vs0.16,P<0.05);Gly16纯合子在夜间哮喘患者的频率分布较非夜间哮喘患者明显增高(35.3%vs13.5%,P<0.01);Gln27纯合子的个体较Glu27纯合子和Glu/Gln27的杂合子个体气道激发试验所用Mch剂量明显低犤(0.205±0.275)vs(2.11±3.00)vs(1.575±0.828)μmol,P<0.05犦;16,27位β2AR基因型对哮喘患者的气道可逆性的改善、总IgE水平、肺功能的损害无影响。结论Gly16/β2AR纯合基因型与我国北方汉族哮喘患者的遗传易感性有关,并与哮喘患者夜间症状加重明显有关,但不是哮喘发病的独立危险因素;

β_2肾上腺素能受体基因与小儿哮喘的关系

目的 :探讨β2 肾上腺素能受体 (β2 AR)基因与小儿哮喘的关系。方法 :采用聚合酶链反应 (PCR)技术扩增β2 AR 5′端基因片段 ,对 6 5例哮喘患儿和 2 0例正常对照进行分析。结果 :哮喘组中 2 2例及对照组中 6例存在β2 AR基因片段的缺失 ,缺失率分别为 33.8% (2 2 / 6 5 )和 30 % (6 / 2 0 ) ,哮喘组与对照组相比差异无显著性 ,但哮喘组中重度与轻度、中度比较 β2 AR基因缺失率高。结论 :β2 AR基因片段的缺失与哮喘发病无关 ,但与重度哮喘患者的发病有关。

缓激肽β_2受体基因启动子区SSCP带型与新疆哈萨克族人原发性高血压的相关性分析

目的:探讨缓激肽β2 受体基因启动子区 91 位至 7 位基因变异与新疆哈萨克族人原发性高血压的关系。方法:运用聚合酶链反应-单链构象多态性分析(PCR SSCP)方法,对 118 例收缩压≥150 mmHg和/或舒张压≥95 mmHg的哈萨克族原发性高血压病人和 65 例年龄、性别、族别、BMI相匹配的血压<135/85 mmHg的正常血压者,分别进行缓激肽β2 受体基因启动子区 91位至 7位基因多态性检测,观察不同SSCP带型在高血压病人组和正常血压对照组中的分布频率。结果:新疆哈萨克族人缓激肽β2 受体基因启动子区存在 A、B、C 3 种带型,A、B、C带型在原发性高血压病人组和正常血压对照组的分布频率分别为 0.28、0.37; 0.22、0.23; 0.50、0.40。3种带型的分布频率在两组间差异无统计学意义(χ2= 2.002, P=0.367)。结论:新疆哈萨克族人缓激肽β2 受体基因启动子区 91位至 7位存在有3种SSCP带型,提示该区域可能存在有基因变异,但该变异可能与哈萨克族人原发性高血压不相关。

猪β_2-肾上腺素能受体基因的克隆与鉴定

β2 肾上腺素能受体 (β2 adrenergicreceptor ,β2 AR)是 β AR的一种亚型。本研究根据猪的 β2 ARcDNA序列设计了 1对引物 ,以肝脏基因组DNA为模板 ,经PCR获取了一约 1 3kb目的基因片段。将该片段克隆入 pMD18 T载体 ,构建猪 β2 AR基因重组质粒 pMDAR。经PCR反应、酶切鉴定和序列分析证实 β2 AR基因已成功克隆。为进一步研究β2 AR的功能、调控 β2 AR和研制 β2 AR型基因工程疫苗奠定了基础。

β_2-肾上腺素能受体基因+46位多态性与新疆哈萨克族人超重肥胖的关系

目的:通过观察β2-肾上腺素能受体基因(β 2-adrenergic receptor, β 2-AR、ADRB2)+46A→G (Arg16/Gly)多态性与体重指数(BMI)的关系,研究其与哈萨克族人超重肥胖的关系.方法:采集120例35～65岁哈萨克族人的遗传标本,按WHO超重和肥胖划分标准以BMI<25 kg/m 2、25～29.9 kg/m 2、≥30 kg/m 2 将人群划分为正常、超重及肥胖3组,采用allele-specific PCR方法检测和分析该人群β 2-AR基因+46A→G多态性,观察各基因型和等位基因频率在不同BMI水平的分布及其与超重肥胖的关系. 结果:该人群β 2-AR+46位基因型频率为AA 0.39,AG 0.37,GG 0.24;A等位基因频率为0.58,G等位基因频率为0.42;3组间相应AA、AG、GG及A、G基因型和等位基因频率分别为0.37、0.39、0.24、0.56 、0.44;0.47、0.33、0.20、0.63、0.37和0.29、0.38、0.33、0.48、0.52,3组基因型及等位基因频率差异均无统计学意义(P＞0.05). 结论:哈萨克族人群β 2-AR基因存在+46 A→G (Arg16/Gly)多态性,但该位点多态性与哈萨克族人群超重肥胖无关.

Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting β2-adrenergic receptor

Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria baicalensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of biophysical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential b2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.

缓激肽β_2受体基因多态性与ACEI降压疗效个体差异

目的 探讨缓激肽β2 受体基因启动子 -5 8T/C等位基因在原发性高血压患者中的分布频率及其多态性与ACEI降压疗效之间的关系。方法 选择 2 83例 1-2级原发性高血压患者 ,给予血管紧张素转换酶抑制剂 (ACEI)咪达普利或贝那普利治疗 6周 ,观察降压疗效。采用聚合酶链反应 (PCR)结合单链构象多态性 (SSCP)方法检测缓激肽 β2 受体基因型。结果 本研究中三种基因型频率分别为CC 2 6 5 % ,TC 61 5 % ,TT 12 0 % ,等位基因频率为C 0 5 9,T 0 41。ACEI治疗后 ,CC、TC和TT组收缩压下降值分别为 ( 10 9± 11 8)mmHg ,( 15 9± 10 7)mmHg ,( 15 1± 13 2 )mmHg ;舒张压下降值分别为 ( 8 7± 6 0 )mmHg ,( 8 9± 5 9)mmHg ,( 11 2± 5 5 )mmHg ,三组之间比较均有统计学差异 ,P <0 0 1。 结论 缓激肽 β2 受体基因启动子 -5 8T/C多态性与原发性高血压患者ACEI降压疗效相关 。

β_2-AR基因A46G多态性与原发性高血压、2型糖尿病的关系

目的 :探讨 β2 肾上腺素能受体 (Beta 2 adrenergicreceptor,β2 AR)基因A4 6G多态性与原发性高血压和2型糖尿病的关系。方法 :应用聚合酶链反应 限制性片段长度多态性的方法 ,检测 1 2 3例健康人 ,1 0 9例原发性高血压患者及 1 0 8例 2型糖尿病病人的 β2 AR基因型。用生化技术测定研究对象的空腹血糖、总胆固醇、甘油三脂、高密度脂蛋白 胆固醇。结果 :原发性高血压组G等位基因频率 4 6 .3% ,显著高于正常对照组 35 .8% (χ2 =5 .33,P<0 .0 5 ) ,2型糖尿病组G等位基因频率 4 3.5 % ,与对照组差别无显著性意义 (χ2 =3.0 9,P >0 .0 5 )。结论 :β2 AR基因可能是中国武汉汉族人原发性高血压的重要遗传因素 ,但该基因多态性与

新疆哈萨克族β_2肾上腺素能受体基因G252A和C523T多态性与原发性高血压的关系

目的:探讨β2肾上腺素能受体(β2-AR)基因G252A和C523T单核苷酸多态性(SNPs)与新疆哈萨克族原发性高血压(EH)的相关性。方法:采用多聚酶链式反应-限制性酶切片段长度多态性技术(PCR-RFLP),对新疆哈萨克族人进行β2-AR基因G252A、C523T多态性检测,观察G252A与C523T各等位基因、基因型和联合基因型在EH组和正常血压(NT)组中的分布,分析其与该民族高血压的关系。结果:新疆哈萨克族人存在G252A多态及AA、AG、GG3种基因型和C523T多态及TT、TC、CC3种基因型,各基因型在研究人群中的分布均符合Hardy-Weinberg平衡。两位点6种基因型和4种等位基因频率在EH组和NT组间的分布均无统计学差异((P>0.05)。对G252A的GG基因型、C523T的CC基因型组成联合基因型与其他基因型总和进行分析,在收缩压、舒张压、平均动脉压水平方面差异均无统计学意义(P>0.05)。结论:新疆哈萨克族人β2-AR基因存在G252A与C523T多态性,但这两种多态性可能与哈萨克族高血压不相关。

肺腺癌组织中前列腺素内过氧化物合酶2表达水平与表皮生长因子受体基因突变的相关性分析

目的 分析肺腺癌组织中前列腺素内过氧化物合酶2(PTGS2)表达水平与表皮生长因子受体(EGFR)基因突变的相关性。方法 选取57例肺腺癌患者为研究对象,收集肺腺癌组织及其相应癌旁组织。采用实时荧光定量PCR(RT-PCR)法检测癌组织及癌旁组织中PTGS2 mRNA表达水平;采用免疫组织化学法分析PTGS2蛋白表达;采用RT-PCR法检测癌组织及癌旁组织EGFR基因突变情况。分析肺腺癌患者临床病理参数与PTGS2 mRNA水平、EGFR基因突变情况的关系。采用Spearman秩相关分析探讨肺腺癌患者EGFR基因突变情况与PTGS2 mRNA水平的相关性。结果 57例肺腺癌患者中,5例癌旁组织EGFR基因突变型患者,其对应癌组织也均发生突变,且为同一突变类型。26例(45.61%)癌组织EGFR基因突变型患者,未发现双重突变,其中19外显子突变17例(29.82%),均为缺失突变;21外显子突变9例(15.79%),均为L858R点突变。癌组织中PTGS2mRNA表达水平、PTGS2蛋白阳性率及EGFR基因突变型比例高于癌旁组织,EGFR基因野生型比例低于癌旁组织(P<0.01)。肺腺癌患者性别、TNM分期、吸烟与PTGS2 mRNA表达水平、EGFR基因突变情况有关(P<0.05或0.01)。EGFR基因突变型PTGS2 mRNA表达水平高于EGFR基因野生型(P<0.01)。肺腺癌患者EGFR基因突变与PTGS2 mRNA表达水平呈正相关(r=0.512,P<0.01)。结论 肺腺癌患者癌组织中PTGS2mRNA表达水平及PTGS2蛋白阳性率升高,且与EGFR基因突变关系密切,二者可能共同影响疾病进程。