河北汉族终末期肾功能衰竭患者HLA-A、B位点基因多态性分析
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摘要
目的:研究河北汉族终末期肾功能衰竭患者HLA-A、B位点基因多态性,寻找HLA-A、B位点与终末期肾功能衰竭相关基因。方法:采用聚合酶链反应序列特异性引物(PCR-SSP)分型方法对河北汉族490例终末期肾功能衰竭患者进行HLA-A、B位点基因分型,计算基因频率,利用Haldane相对危险度修正公式计算该基因与终末期肾功能衰竭发生的相对危险度,相对危险度与1的显著性检测利用Fisher精确P值法计算,为避免偶然性造成的显著性差异,乘以该位点所比较的抗原总数对P进行修正。结果:490例终末期肾功能衰竭患者中共检出HLA-A位点抗原15个,检出频率最高的等位基因为A*02(0.341155),其次是A*24(0.212161)、A*11(0.203201)、A*30(0.077001)、A*03(0.053136)、A*01(0.050996);HLA-B位点抗原35个,基因频率最高的为B*13(0.146657),其次是B*4002G(0.080303)、B*1501G(0.077001)、B*51(0.068252)、B*4001G(0.066078)、B*35(0.062825),以上12个基因为HLA-A、B位点常见等位基因(基因频率GF>0.05)。患者组A*11、A*24、B*13的RR与1的显著性检测结果差异有统计学意义,且其RR均>1,证明这3个基因与终末期肾功能衰竭的发生显著关联。结论:推测A*11、A*24、B*13是河北汉族终末期肾功能衰竭的易感基因。
Objective:To investigate the polymorphism of HLA-A and B loci in patients with end-stage renal disease(ESRD)in Hebei Han nationality and find related genes of HLA-A,B loci and ESRD.Method:HLA-A and B loci were genotyped in 490 patients with ESRD by polymerase chain reaction sequence specific primer(PCR-SSP)typing method,then calculated the gene frequency,and the Haldane corrected Formula was used to calculate the relative risk of the gene and the occurrence of the disease,the relative risk of significant test using Fisher's exact P value calculation,in order to avoid significant differences caused by chance,revised the Pvalue by multiplied the total number of antigens.Result:A total of 15 HLA-A site antigens detected in 490 patients with ESRD.The highest frequency of alleles was A*02(0.341155),followed by A*24(0.212161),A*11(0.203201),A*30(0.077001),A*03(0.053136)and A*01(0.050996).And 35 HLA-B site antigens were detected.The highest frequency of alleles was B*13(0.146657),followed by B*4002 G(0.080303),B*1501 G(0.077001),B*51(0.068252),B*4001 G(0.066078)and B*35(0.062825).There was a significant difference between RR and 1 in A*11,A*24 and B*13 patients,and all 3 genes RR>1,which proved that these 3 genes were significantly associated with ESRD.Conclusion:It is speculated that A*11,A*24 and B*13 are susceptible genes of ESRD in Hebei Han nationality.
Objective:To investigate the polymorphism of HLA-A and B loci in patients with end-stage renal disease(ESRD)in Hebei Han nationality and find related genes of HLA-A,B loci and ESRD.Method:HLA-A and B loci were genotyped in 490 patients with ESRD by polymerase chain reaction sequence specific primer(PCR-SSP)typing method,then calculated the gene frequency,and the Haldane corrected Formula was used to calculate the relative risk of the gene and the occurrence of the disease,the relative risk of significant test using Fisher's exact P value calculation,in order to avoid significant differences caused by chance,revised the Pvalue by multiplied the total number of antigens.Result:A total of 15 HLA-A site antigens detected in 490 patients with ESRD.The highest frequency of alleles was A*02(0.341155),followed by A*24(0.212161),A*11(0.203201),A*30(0.077001),A*03(0.053136)and A*01(0.050996).And 35 HLA-B site antigens were detected.The highest frequency of alleles was B*13(0.146657),followed by B*4002 G(0.080303),B*1501 G(0.077001),B*51(0.068252),B*4001 G(0.066078)and B*35(0.062825).There was a significant difference between RR and 1 in A*11,A*24 and B*13 patients,and all 3 genes RR>1,which proved that these 3 genes were significantly associated with ESRD.Conclusion:It is speculated that A*11,A*24 and B*13 are susceptible genes of ESRD in Hebei Han nationality.
引文
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[7]欧剑锋,任晖,张茜,等.西北高原汉族人群人类白细胞抗原-A、B、DRB1基因多态性与慢性肾功能衰竭相关性分析[J].临床肾脏病杂志,2014,14(10):590-593.
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[9]夏家安,曹奎杰,李王霞,等.肺结核病患者与HLADRB1等位基因的关联[J].临床血液学杂志(输血与检验),2014,27(10):842-844.
[10]罗欢,高宏君.HLA基因多态性与慢性肾衰竭的相关性研究进展[J].医学综述,2013,19(22):4049-4051.
[2]赵桐茂.HLA分型原理及应用[M].上海:上海科学技术出版社,1984:209-211.
[3]肖露露,于立新,陈洪涛,等.慢性肾小球肾炎与HLA免疫遗传强关联[J].中华泌尿外科杂志,1999,20(10):592-594.
[4]刘伟,李代红.肾移植与HLA基因多态性研究[J].广东医学,2013,34(9):1361-1364.
[5]刘楠,袁方,梁飞,等.人类白细胞抗原多态性与慢性肾功能衰竭的遗传易性研究[J].军事医学科学院院刊,2009,33(1):33-36.
[6]韩志明,肖露露,于立新,等.南方汉族等候肾移植终末期肾功能衰竭患者HLA基因多态性分析[J].现代泌尿外科杂志,2010,15(2):110-113.
[7]欧剑锋,任晖,张茜,等.西北高原汉族人群人类白细胞抗原-A、B、DRB1基因多态性与慢性肾功能衰竭相关性分析[J].临床肾脏病杂志,2014,14(10):590-593.
[8]倪文旭,郑山根,夏琳.406例肾移植受者HLA-ABDR基因频率分析[J].临床血液学杂志(输血与检验),2011,24(12):704-706.
[9]夏家安,曹奎杰,李王霞,等.肺结核病患者与HLADRB1等位基因的关联[J].临床血液学杂志(输血与检验),2014,27(10):842-844.
[10]罗欢,高宏君.HLA基因多态性与慢性肾衰竭的相关性研究进展[J].医学综述,2013,19(22):4049-4051.