IL-10基因单核苷酸多态性与急性淋巴细胞白血病易感性的相关性研究

目的 探讨IL-10基因单核苷酸多态性与ALL发病易感性的关系.方法 选取2007年1月至2009年12月北京大学第一医院、北京市道培医院115例ALL缓解患者,同时选取323名体检健康者作为对照组.采集ALL患者的骨髓以及健康对照者的外周血标本,提取DNA.设计IL-10启动子区-819C/T、-592A/C引物做PCR,应用限制性内切酶Msl Ⅰ、HpyCH4Ⅲ分析其限制性片段长度多态性,并测序验证;同时分析IL-10基因-819位点、-592位点各基因型构成及等位基因在ALL患者组和健康对照组间的差异.用实时定量PCR检测ALL患者EB病毒DNA和BCR/ABL融合基因,分析IL-10基因-819位点、-592位点各基因型构成及等位基因在EB病毒阳性和阴性组间、BCR/ABL融合基因阳性和阴性组间的差异.结果 ALL患者组IL-10基因-819位点的-819CC、-819TT、-819CT基因型比例分别为14.8%(17/115)、45.2%(52/115)、40.0%(46/115),-592位点的-592AA、-592CC、-592AC基因型比例分别为43.5%(50/115)、16.5%(19/115)、40.0%(46/115);健康对照组-819位点的-819CC、-819TT、-819CT基因型比例分别为9.9%(32/323)、16.4%(53/323)、73.7%(238/323),-592位点的-592AA、-592CC、-592AC基因型比例分别为11.8%(38/323)、15.5%(50/323)、72.8%(235/323),ALL患者组与健康对照组间-819和-592位点基因型构成差异均有统计学意义(x2值分别为46.000和54.550,P均＜0.05＝.ALL患者组-819T等位基因比例为65.2%(150/230),-592A等位基因比例为63.5%(146/230),而健康对照组分别为53.5%(344/646)和48.1%(311/646),差异均有统计学意义(x2值分别为9.877和15.986,P均＜0.05＝.ALL患者中42例检测了EB病毒DNA,其中EB病毒阳性22例,EB病毒阴性20例.EB病毒阳性组-819位点的-819CC、-819TT、-819CT基因型比例分别为9.1%(2/22)、40.9%(9/22)、50.0%(11/22),-592位点的-592AA、-592CC、-592AC基因型比例分别为31.8%(7/22)、13.6%(3/22)、54.5%(12/22),EB病毒阴性组分别为35.0%(7/20)、45.0%(9/20)、20.0%(4/20)和35.0%(7/20)、45.0%(9/20)、20.0%(4/20),2组基因型构成差异均无统计学意义(P均＞0.05).ALL患者中36例进行了BCR/ABL融合基因检测,其中阳性20例,阴性16例.BCR/ABL融合基因阳性组-819位点的-819CC、-819TT、-819CT基因型比例分别为0%(0/20)、45.0%(9/20)、55.0%(11/20),-592位点的-592AA、-592CC、-592AC基因型比例分别为45.0%(9/20)、5.0%(1/20)、50.0%(10/20),BCR/ABL融合基因阴性组分别为18.8%(3/16)、50.0%(8/16)、31.3%(5/16)和50.0%(8/16)、18.8%(3/16)、31.3%(5/16),2组基因型构成差异均无统计学意义(P均＞0.05).结论 IL-10基因-819位点TT基因型和-592位点AA基因型人群易患ALL.

Abstract：

Objective To observe the relationship of IL-10 gene single nucleotide polymorphism and the susceptibility to ALL. Methods The bone marrow and peripheral blood samples from 115 ALL patients and 323 healthy controls were collected in Peking University First Hospital and Beijing Dao-pei Hospital from January 2007 to December 2009. The DNA were extracted from all samples. The primers of -819C/T and -592A/C in the promoter region of IL-10 gene were designed for the PCR. The restrictive fragment length polymorphism of IL-10 gene was analyzed by using restrictive enzyme Msl Ⅰ and HpyCH4 Ⅲ.Sequencing was done in part of these samples to confirm the results of PCR. The differences of genotypes and allele ratio of -819 and -592 sites were analyzed between the ALL patients and healthy controls. Real-time quantitative PCR was performed to detect the EB virus (EBV) infection and the expression of BCR/ABL fusion gene. The differences of genotypes and allele ratio of -819 and -592 sites were analyzed between the positive and negative group. Results The genotype ratios of -819CC, -819TT, - 819CT, -592AA,- 592CC and - 592AC were 14. 8% ( 17/115 ), 45.2% ( 52/115 ), 40. 0% ( 46/115 ), 43.5% ( 50/115 ),16. 5% ( 19/115 ), 40. 0% ( 46/115 ) in ALL patients, and were 9. 9% ( 32/323 ), 16. 4% ( 53/323 ),73.7% ( 238/323 ), 11.8% ( 38/323 ), 15.5% ( 50/323 ), 72. 8% ( 235/323 ) in the healthy controls,respectively. The genotypes of -819 and -592 sites had statistically significant differences between the two groups(x2 values were 46.000 and 54.550, all P ＜ 0. 05 ). The allele ratio of -819T and -592A were (65.2%, 150/230) and (63.5%, 146/230) in ALL patients, while they were 53.5% (344/646) and 48. 1% (311/646)in the healthy controls. There were statistically significant differences between the two groups (x2 values were 9. 877 and 15.986, all P ＜ 0. 05 ). The EBV DNA were detected in 42 ALL patients,among which 22 were positive and 20 were negative. The genotype ratios of -819CC, -819TT, -819CT,-592AA, - 592CC, - 592AC in EBV positive group were 9. 1% ( 2/22 ), 40. 9% ( 9/22 ), 50. 0%(11/22) ,31.8% ( 7/22 ), 13.6% ( 3/22 ), 54. 5% ( 12/22 ), while they were 35.0% ( 7/20 ), 45.0%(9/20) ,20. 0% (4/20) ,35.0% (7/20) ,45.0% (9/20) ,20. 0% (4/20) in the EBV negative group. The genotypes of -819 and -592 sites showed no statistical differences between the two groups( all P ＞ 0. 05 ).The BCR/ABL fusion gene were detected in 36 ALL patients, among which 20 were positive and 16 were negative. The genotype ratios of - 819CC, - 819TT, - 819CT, - 592AA, - 592CC, - 592AC in BCR/ABL positive group were 0% (0/20) ,45.0% (9/20) ,55.0% ( 11/20), 45. 0% (9/20) ,5.0% (1/20) ,50. 0%( 10/20), while they were 18. 8% ( 3/16 ), 50. 0% ( 8/16), 31.3% ( 5/16 ), 50. 0% ( 8/16 ), 18. 8%(3/16), 31.3 % (5/16)in the BCR/ABL negative group. The genotypes of -819 and -592 sites showed no statistical differences between the two groups ( all P ＞ 0. 05 ). Conclusion The population with - 819TT and - 592AA genotype of IL-10 gene shows susceptibility to ALL.     

IL-10基因单核苷酸多态性与急性淋巴细胞白血病易感性的相关性研究

Objective To observe the relationship of IL-10 gene single nucleotide polymorphism and the susceptibility to ALL. Methods The bone marrow and peripheral blood samples from 115 ALL patients and 323 healthy controls were collected in Peking University First Hospital and Beijing Dao-pei Hospital from January 2007 to December 2009. The DNA were extracted from all samples. The primers of -819C/T and -592A/C in the promoter region of IL-10 gene were designed for the PCR. The restrictive fragment length polymorphism of IL-10 gene was analyzed by using restrictive enzyme Msl Ⅰ and HpyCH4 Ⅲ.Sequencing was done in part of these samples to confirm the results of PCR. The differences of genotypes and allele ratio of -819 and -592 sites were analyzed between the ALL patients and healthy controls. Real-time quantitative PCR was performed to detect the EB virus (EBV) infection and the expression of BCR/ABL fusion gene. The differences of genotypes and allele ratio of -819 and -592 sites were analyzed between the positive and negative group. Results The genotype ratios of -819CC, -819TT, - 819CT, -592AA,- 592CC and - 592AC were 14. 8% ( 17/115 ), 45.2% ( 52/115 ), 40. 0% ( 46/115 ), 43.5% ( 50/115 ),16. 5% ( 19/115 ), 40. 0% ( 46/115 ) in ALL patients, and were 9. 9% ( 32/323 ), 16. 4% ( 53/323 ),73.7% ( 238/323 ), 11.8% ( 38/323 ), 15.5% ( 50/323 ), 72. 8% ( 235/323 ) in the healthy controls,respectively. The genotypes of -819 and -592 sites had statistically significant differences between the two groups(x2 values were 46.000 and 54.550, all P ＜ 0. 05 ). The allele ratio of -819T and -592A were (65.2%, 150/230) and (63.5%, 146/230) in ALL patients, while they were 53.5% (344/646) and 48. 1% (311/646)in the healthy controls. There were statistically significant differences between the two groups (x2 values were 9. 877 and 15.986, all P ＜ 0. 05 ). The EBV DNA were detected in 42 ALL patients,among which 22 were positive and 20 were negative. The genotype ratios of -819CC, -819TT, -819CT,-592AA, - 592CC, - 592AC in EBV positive group were 9. 1% ( 2/22 ), 40. 9% ( 9/22 ), 50. 0%(11/22) ,31.8% ( 7/22 ), 13.6% ( 3/22 ), 54. 5% ( 12/22 ), while they were 35.0% ( 7/20 ), 45.0%(9/20) ,20. 0% (4/20) ,35.0% (7/20) ,45.0% (9/20) ,20. 0% (4/20) in the EBV negative group. The genotypes of -819 and -592 sites showed no statistical differences between the two groups( all P ＞ 0. 05 ).The BCR/ABL fusion gene were detected in 36 ALL patients, among which 20 were positive and 16 were negative. The genotype ratios of - 819CC, - 819TT, - 819CT, - 592AA, - 592CC, - 592AC in BCR/ABL positive group were 0% (0/20) ,45.0% (9/20) ,55.0% ( 11/20), 45. 0% (9/20) ,5.0% (1/20) ,50. 0%( 10/20), while they were 18. 8% ( 3/16 ), 50. 0% ( 8/16), 31.3% ( 5/16 ), 50. 0% ( 8/16 ), 18. 8%(3/16), 31.3 % (5/16)in the BCR/ABL negative group. The genotypes of -819 and -592 sites showed no statistical differences between the two groups ( all P ＞ 0. 05 ). Conclusion The population with - 819TT and - 592AA genotype of IL-10 gene shows susceptibility to ALL.     

IL-10基因单核苷酸多态性与急性淋巴细胞白血病易感性的相关性研究

Objective To observe the relationship of IL-10 gene single nucleotide polymorphism and the susceptibility to ALL. Methods The bone marrow and peripheral blood samples from 115 ALL patients and 323 healthy controls were collected in Peking University First Hospital and Beijing Dao-pei Hospital from January 2007 to December 2009. The DNA were extracted from all samples. The primers of -819C/T and -592A/C in the promoter region of IL-10 gene were designed for the PCR. The restrictive fragment length polymorphism of IL-10 gene was analyzed by using restrictive enzyme Msl Ⅰ and HpyCH4 Ⅲ.Sequencing was done in part of these samples to confirm the results of PCR. The differences of genotypes and allele ratio of -819 and -592 sites were analyzed between the ALL patients and healthy controls. Real-time quantitative PCR was performed to detect the EB virus (EBV) infection and the expression of BCR/ABL fusion gene. The differences of genotypes and allele ratio of -819 and -592 sites were analyzed between the positive and negative group. Results The genotype ratios of -819CC, -819TT, - 819CT, -592AA,- 592CC and - 592AC were 14. 8% ( 17/115 ), 45.2% ( 52/115 ), 40. 0% ( 46/115 ), 43.5% ( 50/115 ),16. 5% ( 19/115 ), 40. 0% ( 46/115 ) in ALL patients, and were 9. 9% ( 32/323 ), 16. 4% ( 53/323 ),73.7% ( 238/323 ), 11.8% ( 38/323 ), 15.5% ( 50/323 ), 72. 8% ( 235/323 ) in the healthy controls,respectively. The genotypes of -819 and -592 sites had statistically significant differences between the two groups(x2 values were 46.000 and 54.550, all P ＜ 0. 05 ). The allele ratio of -819T and -592A were (65.2%, 150/230) and (63.5%, 146/230) in ALL patients, while they were 53.5% (344/646) and 48. 1% (311/646)in the healthy controls. There were statistically significant differences between the two groups (x2 values were 9. 877 and 15.986, all P ＜ 0. 05 ). The EBV DNA were detected in 42 ALL patients,among which 22 were positive and 20 were negative. The genotype ratios of -819CC, -819TT, -819CT,-592AA, - 592CC, - 592AC in EBV positive group were 9. 1% ( 2/22 ), 40. 9% ( 9/22 ), 50. 0%(11/22) ,31.8% ( 7/22 ), 13.6% ( 3/22 ), 54. 5% ( 12/22 ), while they were 35.0% ( 7/20 ), 45.0%(9/20) ,20. 0% (4/20) ,35.0% (7/20) ,45.0% (9/20) ,20. 0% (4/20) in the EBV negative group. The genotypes of -819 and -592 sites showed no statistical differences between the two groups( all P ＞ 0. 05 ).The BCR/ABL fusion gene were detected in 36 ALL patients, among which 20 were positive and 16 were negative. The genotype ratios of - 819CC, - 819TT, - 819CT, - 592AA, - 592CC, - 592AC in BCR/ABL positive group were 0% (0/20) ,45.0% (9/20) ,55.0% ( 11/20), 45. 0% (9/20) ,5.0% (1/20) ,50. 0%( 10/20), while they were 18. 8% ( 3/16 ), 50. 0% ( 8/16), 31.3% ( 5/16 ), 50. 0% ( 8/16 ), 18. 8%(3/16), 31.3 % (5/16)in the BCR/ABL negative group. The genotypes of -819 and -592 sites showed no statistical differences between the two groups ( all P ＞ 0. 05 ). Conclusion The population with - 819TT and - 592AA genotype of IL-10 gene shows susceptibility to ALL.     

DNA修复基因XPD、XPA单核苷酸多态性与乳腺癌发病风险的相关性研究

目的探讨人类着色性干皮病基因D(XPD)的rs238406,rs13181,rs3810366,rs1799793,rs50872及着色性干皮病基因A(XPA)的rs1800975单核苷酸多态性与南京地区女性乳腺癌发病风险、病理特征与乳腺癌相关激素受体水平的相关性。方法采用病例-对照研究,选取298例女性乳腺癌患者作为病例组,298例健康女性作为对照组,用Sequenom Mass Array技术检测6个多态性位点的基因型,Logistic回归模型分析不同基因型与乳腺癌发生、病理特征和相关激素受体水平包括雌激素受体(ER)、孕激素受体(PR)及原癌基因人类表皮生长因子受体2(HER2或Cer B-2)的关系。结果 rs3810366(χ2=14.993,P=0.001)、rs1800975(χ2=8.336,P=0.015)、rs50872(χ2=8.735,P=0.013)位点的各基因型在两组中分布差异有统计学意义。rs3810366 CG基因型(OR=0.54,95%CI:0.37~0.78)在乳腺癌组中的频率(31.54%)低于对照组(46.98%),GG/CG基因型发生乳腺癌的风险是健康人的0.71倍(OR=0.71,95%CI:0.51~1.00)。rs1800975位点的AG(OR=0.58,95%CI:0.39~0.85)、AA(OR=0.65,95%CI:0.42~0.90)、AA/AG(OR=0.60,95%CI:0.43~0.86)基因型与乳腺癌的发病风险均呈现负相关(OR1);rs50872 CT(OR=1.64,95%CI:1.16~2.32)及TT/CT(OR=1.66,95%CI:1.18~2.30)是乳腺癌的风险因素。ER及Cer B-2水平可影响rs3810366基因位点在病例组与对照组中分布(P0.01)。PR与Cer B-2水平影响rs1800975基因位点在两组中的分布(P0.05)。对rs50872位点进行分析,在ER、PR及Cer B-2水平正常时,基因型在病例组与对照组中分布差异有统计学意义(P0.01)。结论 XPD基因的rs3810366、rs1800975及rs50872位点的单核苷酸多态性与乳腺癌的发生风险具有相关性。对于不同基因位点,ER、PR及Cer B-2的水平与乳腺癌的发生、发展有关。     

淋巴系统肿瘤发病与EB病毒和IL-10基因多态性的关系

淋巴系统肿瘤与病毒感染有密切关系,EBV(Epstein-Barn Virus)转染正常B细胞会造成B细胞发生类似肿瘤的永生化,是最可疑的致病因素.EBV的Bcrfl编码框又称为病毒IL-10,和人类IL-10同源,具有和IL-10相似的免疫抑制作用.IL-10是一种重要的免疫调节因子,其分泌水平的高低影响着淋巴系统疾病的发生和发展;IL-10启动子区的SNP位点基因型也与IL-10的分泌水平相关.本综述探讨淋巴系统肿瘤,EBV感染以及IL-10基因多态性之间的密切关系.     

IL2RA,IL-10基因单核苷酸多态性与儿童EBV-HLH相关性的研究

目的:探讨IL2RA,IL-10基因单核苷酸多态性(SNPs)与儿童EBV-HLH发病的关系及关联SNPs对患儿预后的影响。方法:对EBV-HLH组(51例),EBV相关传染性单核细胞增多症(EBV-IM)组(48例)和EBV血清阳性的健康儿童组(52例),用SNaPshot基因分型检测技术检测IL2RA基因的rs2104286、rs12722489、rs11594656位点和IL-10基因的rs1800896、rs1800871、rs1800872位点的基因型,分析各SNP的基因型频率、等位基因频率在每组的分布差异;以关联SNPs进行生存分析。结果:IL-10基因rs1800896位点AA基因型在EBV-HLH组的出现频率高于IM组(58.8%vs 25.0%)和健康对照组(58.8%vs 26.9%);A等位基因在EBV-HLH组的出现频率高于IM组(74.5%vs 54.2%)和健康对照组(74.5%vs 57.7%)。IL-2RA基因rs2104286位点AA基因型在EBV-HLH组的出现频率高于IM组(54.9%vs 27.1%)及健康对照组(54.9%vs 25.0%);A等位基因在EBV-HLH组的出现频率高于IM组(70.6%vs 51.0%)及健康对照组(70.6%vs 46.2%)。不同基因型的EBV-HLH患儿的Kaplan-Meier生存曲线,差异无统计学意义。结论:IL-10基因rs1800896位点及IL-2RA基因rs2104286位点多态性可能与儿童EBV-HLH发病相关,两位点的AA基因型、A等位基因可能是儿童EBV-HLH的易感危险因素。     

PALB2基因单核苷酸多态性与乳腺癌易感性的相关性

目的探究乳腺癌易感基因PALB2单核苷酸多态性与乳腺癌及其临床病理学参数的关系。方法收集280例乳腺癌患者作为病例组,288例健康人作为健康人对照组。以Mass ARRAY基因分型技术检测多态性位点rs447529、rs249954和rs120963在病例组和健康人对照组中的基因型分布,采用Logistic回归模型分析各基因型与乳腺癌易感性及其临床病理学参数的关系。结果 rs447529位点各基因型在病例组和健康人对照组中的分布差异无统计学意义(P0.05),rs120963位点的突变基因型TC(OR=2.46,95%CI=1.70~3.56,P0.01)、CC(OR=3.78,95%CI=1.58~9.01,P0.05)及TC/CC(OR=2.61,95%CI=1.82~3.72,P0.01)在病例组的分布频率均显著高于健康人对照组,rs249954位点的突变基因型CT(OR=1.99,95%CI=1.37~2.88,P0.01)、TT(OR=3.22,95%CI=1.75~5.92,P0.01)及CT/TT(OR=2.16,95%CI=1.51~3.09,P0.01)在病例组中的分布频率亦均显著高于健康人对照组。按照月经状态和初潮年龄进行分层分析,这2个多态性位点的各基因型在病例组中分布频率均显著高于健康人对照组(P0.05)。rs120963和rs249954与乳腺癌患者的肿瘤体积及淋巴结转移相关。结论 PALB2基因rs120963和rs249954位点基因多态性是乳腺癌发病的危险因素,并与乳腺癌的病理组织学参数相关。     

血清IL-10水平及其基因-1082A/G位点单核苷酸多态性与胃窦癌恶病质的关系

目的探讨胃窦癌病人血清细胞因子白细胞介素10（IL-10）水平及-1082A/G位点单核苷酸多态性与恶病质发生的关系。方法采用放射免疫学方法检测150例胃窦癌病人及135例健康人（对照组）血清IL-10水平。用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测胃窦癌病人IL-10基因-1082A/G位点单核苷酸多态性。结果胃窦癌病人血清IL-10水平较对照组显著升高（Z=-11.862,P〈0.001）,胃窦癌Ⅲ、Ⅳ期病人血清IL-10水平较Ⅰ、Ⅱ期显著升高（Z=-10.028,P〈0.001）。胃窦癌恶病质病人血清IL-10水平较非恶病质病人显著升高（Z=-10.369,P〈0.001）。Logistic回归分析显示,IL-10为恶病质发生的高风险性因素（OR=1.559,95%CI=1.299-1.870,P〈0.001）。单核苷酸多态性分析显示,胃窦癌恶病质病人IL-10基因-1082G等位基因频率较非恶病质病人显著升高（χ2=3.953,P〈0.05）。胃窦癌恶病质病人IL-10基因-1082AG基因型频率较非恶病质病人显著升高（χ2=4.511,P〈0.05）。Logistic回归分析显示,校正肿瘤分期后,IL-10基因-1082AG基因型为胃窦癌恶病质的高风险性因素（OR=2.295,95%CI=1.029-5.117,P〈0.05）。结论血清IL-10水平高及IL-10基因-1082AG基因型与胃窦癌病人恶病质的发生具有相关性。     

白介素10基因多态性与术后脓毒症发生发展的相关研究

目的研究白介素10（IL-10）基因启动子区域中IL-10-592、IL-10-819、IL-101-082基因多态性与术后严重脓毒症易感性及其预后的相关性。方法采用聚合酶链反应（PCR）结合RsaⅠ、MaeⅢ、MnlⅠ限制性内切酶酶切分析法检测116例术后并发严重脓毒症患者和141例健康献血员（对照组）的IL-10-592、IL-10-819、IL-10-1082基因多态性。结果IL-10-1082等位基因1的频率在脓毒症组为59.9％,对照组为50.4%（P<0.05）;IL-10-1082基因型分布频率在脓毒症组和对照组间有显著性差异（P<0.05）;而IL-10-592、IL-10-819等位基因频率及基因型频率在脓毒症组和对照组间均无显著性差异（P均>0.05）;IL-10-592、IL-10-819、IL-10-1082等位基因频率及基因型频率在死亡的与存活的脓毒症患者间均无显著性差异（P均>0.05）。结论IL-10-1082基因多态性与术后严重脓毒症的易感性有关,与其预后不相关;而IL-10-592、IL-10-819基因多态性与术后严重脓毒症的易感性及预后均不相关。     

通用TaqMan探针技术在apoE基因3937T/C单核苷酸多态性检测中的应用

目的　建立一种基于通用TaqMan探针技术的快速、准确且经济的实时荧光PCR方法 ,用于检测apoE基因第四外显子上的一个单核苷酸多态性 (SNP)位点 (3937T/C)。方法　应用PCR RFLP分型方法建立apoE 3937T/C多态性分析的参考样本 ,同时对部分样本进行PCR产物直接测序以验证PCR RFLP分型结果。选择一对能够有效区分 3937T/C多态性的等位基因特异的上游引物 ,配对进行通用TaqMan探针实时PCR扩增 ,然后通过比较两个平行反应达到阈值时所经历的循环数 (Ct)的大小 ,对apoE 3937T/C多态性进行区分。结果　建立的基于通用TaqMan探针技术的实时荧光PCR方法 ,用于apoE基因第四外显子上 3937T/CSNP分析 ,检测结果与PCR RFLP方法、DNA测序法结果完全一致。结论　在进行PCR扩增条件优化的前提下 ,应用通用TaqMan探针对PCR进行全程监测是可行而且是非常经济的 ;基于通用TaqMan探针技术的等位基因特异的实时荧光PCR方法敏感、简单、快速 ,可实现对apoE基因 3937T/C单核苷酸多态性的快速检测 ,而且在其他的SNP位点高通量分析中具有潜在的应用价值     

The single nucleotide polymorphism and haplotype analysis of MDR1 in Chinese diffuse large B cell lymphoma patients

We investigated whether the MDR1 (multidrug resistance 1) gene single nucleotide polymorphism (SNP) and haplotype variants were associated with the susceptibility to diffuse large B-cell lymphoma (DLBCL). A total of 129 DLBCL patients and 208 healthy controls from Jiangsu Han population were enrolled in this study. They were genotyped by polymerase chain reaction-allele specific primers (PCR-ASP) method or DNA direct sequencing at three common loci: C1236T, G2677T/A and C3435T. At locus G2677T/A, allele G and genotype GT were significantly more common in DLBCL (G: OR = 1.48, 95% CI: 1.08–2.02, Pc = 0.03; GT: OR = 1.96, 95% CI: 1.25–3.07, Pc < 0.01), while genotype AT in this locus seemed to be protective (OR = 0.29, 95% CI: 0.02–0.72, Pc = 0.03). TT genotype at locus C3435T showed a risk factor in DLBCL (OR = 2.38, 95% CI: 1.52–3.74, Pc < 0.01). The frequency of T-G-T haplotype was significantly increased in DLBCL group (OR = 5.21, 95% CI: 2.58–10.54, Pc < 0.01); haplotype of G-T in 2677–3435 and diplotype of 2677GT/3435TT were significantly more frequent in DLBCL group (G-T: OR = 3.97, 95% CI: 2.31–6.85, Pc < 0.01; 2677GT/3435TT: OR = 4.55, 95% CI: 2.02–10.22, Pc < 0.01). Our findings demonstrate that G, GT at locus G2677T/A, and TT at locus C3435T might contribute to the susceptibility to DLBCL, as well as haplotype of T-G-T, G-T in 2677–3435 and diplotype of 2677GT/3435TT, while AT at locus G2677T/A might be a protective genotype. These findings could provide evidence that the MDR1 SNPs may modify the susceptibility to DLBCL and shade new lights in disease association studies.     

葡萄糖激酶基因3个标签单核苷酸多态性位点与2型糖尿病的相关性研究

目的探讨葡萄糖激酶(GCK)基因3个标签单核苷酸多态性(tagSNPs)位点rs2971672、rs2268573、rs2300587与2型糖尿病的关系。方法选取2013年8月至2014年12月在中山大学附属中山医院住院的中国南方汉族2型糖尿病患者499例(2型糖尿病组),同时选择同期在该院康体保健中心体检的汉族健康人499例作为对照组,对GCK基因的3个tagSNPs位点采用改良多重高温连接酶检测反应技术(iMLDR)进行基因分型,应用Hardy-Weinberg平衡规律检测标本代表性,采用χ~2检验、Logistic回归分析比较2型糖尿病组和对照组基因型和等位基因频率的差异,并在加性、显性和隐性3种遗传模型下对各SNP位点进行相关性分析。应用Haploview软件构建GCK基因3个tagSNPs位点的单体型,分析是否存在连锁不平衡(LD)及不同的GCK单体型与2型糖尿病易感性的关系。结果 rs2268573、rs2300587的基因型(χ~2=3.361、2.076,均P0.05)和等位基因频率(χ~2=0.222、1.980,均P0.05)在2型糖尿病组和对照组之间差异均无统计学意义。rs2971672的基因型(χ~2=6.896,P0.01)和等位基因分布(χ~2=4.708,P0.05)在2型糖尿病组和对照组之间差异有统计学意义。在显性遗传模式下以及在加性遗传模式下,rs2971672的基因型分布在2型糖尿病组和对照组之间的差异有统计学意义(显性遗传模式下OR=1.74,95%CI:1.17~2.57,P0.01;加性遗传模式下OR=1.51,95%CI:1.06~2.14,P0.05)。GCK基因3个位点中的rs2971672和rs2300587有一个LD域,其中TC、TA、CA3种主要单体型,单体型TA和CA均降低个体患2型糖尿病的风险,OR值分别为0.81(95%CI:0.66~1.00,P0.05)和0.78(95%CI:0.62~0.98,P0.05)。结论在汉族人群中,GCK基因区域的rs2971672位点与糖尿病遗传易感性密切相关,而rs2268573、rs2300587位点与糖尿病遗传易感性无明确相关性。rs2971672和rs2300587的LD域单体型TA和CA均降低个体患2型糖尿病的风险。     

单核苷酸多态性与胃癌易感性的相关性

目的 探讨单核苷酸多态性与胃癌易感性的相关性.方法 应用基因测序仪对120例胃癌患者与112例健康对照者的血样EZH2rs734004、r734005、rs2072407、rs6464926及rs12670401多态性进行测序,再应用组织芯片技术与免疫组化检测80例同一来源胃癌组织与24例癌旁正常胃黏膜组织EZH2蛋白的表达情况.结果 rs12670401最小等位基因C与rs6464926最小等位基因T增加,其胃癌发生风险较大(OR＞1),而其余三种多态性则会降低胃癌发生风险.经Codominant模型、Dominant模型及Recessive模型分析,rs12670401CC与rs6464926TT构成比显著高于对照组,可增加胃癌的发生风险(OR＞1),胃癌患者中杂合基因rs2072407TC、rs734005TC及rs734004CG构成比均显著低于对照组,可降低胃癌的发生风险(OR＜1).结论 EZH2基因单核苷酸多态性与胃癌易感性存在较为紧密的关系,且不同SNP等位基因对胃癌发生具有不同影响.     

急性心肌梗死与巨细胞病毒感染相关性分析

目的探讨急性心肌梗死发病与人巨细胞病毒感染的关系。方法应用间接酶联免疫吸附试验检测急性心肌梗死患者血清中巨细胞病毒特异性IgM,IgA抗体。结果急性心肌梗死患者血清IgM,IgA搞体分别为69·2%和28·8%,明显高出对照组人群,两组间比较差异非常显著。结论急性心肌梗死发病与巨细胞病毒感染有关。     

脂肪酸合成酶基因单核苷酸多态性与妊娠期糖尿病发病的相关性分析

目的探讨脂肪酸合成酶(FASN)基因单核苷酸多态性(SNP)与妊娠期糖尿病(GDM)发病的相关性。方法选取2016年11月至2019年2月在本院行定期产前检查的450例孕妇作为研究对象,将其分为GDM组(232例,确诊GDM)和对照组(218例,正常妊娠)。通过生物信息学数据库筛选FASN基因的4个候选SNP位点,并通过Sequenom MassARRAY对其进行基因分型。采用多因素Logistic回归模型评估候选SNP位点与GDM发病风险的相关性。结果FASN基因SNP位点rs4485435突变基因型(GC/CC)在GDM组的比例显著低于对照组,差异具有统计学意义(P<0.05)。多因素Logistic回归分析显示,在加性模型下,SNP位点rs4485435基因型与GDM发病风险显著相关,差异具有统计学意义(P<0.05);在显性模型下,携带rs4485435 GC+CC基因型的孕妇GDM发病风险明显低于GG基因型,差异具有统计学意义(P<0.05)。结论FASN基因SNP位点rs4485435多态性与GDM发病风险有关。     

血管紧张素原基因单核苷酸多态性与心房颤动的相关性及临床价值研究

目的探讨血管紧张素原(AGT)基因rs5046、rs2148582单核苷酸多态性(SNP)与心房颤动(房颤)的相关性,为临床对房颤的早期诊断及治疗提供参考依据。方法以100例健康体检者为房颤组,108例房颤患者为对照组,并提取两组全血基因组,对血管紧张素原基因rs5046、rs2148582多态性位点进行序列扩增,继而对AGT基因这两个位点的扩增序列进行一代测序分析;并对AGT基因的rs5046、rs2148582位点多态性与房颤的患病风险进行关联分析。结果房颤组rs5046位点的CT、TT基因型频率明显高于对照组(P<0.05),TT基因型对房颤的影响大于CT基因型,C和T等位基因频率比较,差异有统计学意义(P<0.05)。结论 AGT基因rs5046多态性位点与房颤易感性相关,其等位基因T可增加房颤患病的风险。     

DNA修复基因XRCC1单核苷酸多态性与SLE的相关性

目的 分析中国汉族人群SLE患者与健康对照人群中DNA修复基因X线修复交叉互补基因1(XRCC1)的单核苷酸多态性(SNP)分布,探讨其对SLE易感性的影响及与临床表现、实验室指标的关联程度。 方法 用等位基因特异性PCR(AS-PCR)检测39例中国汉族SLE患者和40例中国汉族健康人的XRCC1基因多态位点Arg194Trp、Arg280His和Arg399G1n的SNP型别。 结果 SLE组XRCC1多态位点Arg399G1n等位基因和基因型频率分布与健康人对照组比较具有显著性差异(P<0.05)。XRCC1多态位点Arg194Trp与SLE患者的血液系统损害及抗SS-A抗体的存在相关(P<0.05)。 结论 XRCC1基因SNP与SLE发生及临床表现和自身抗体可能相关。