HLA-DQA_1基因多态性与妊娠期肝内胆汁淤积症的相关性研究
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摘要
目的探讨遵义地区部分妊娠期肝内胆汁淤积症(intrahepatic cholestasis ofpregnancy,ICP)与人类白细胞抗原-DQA_1(human leucocyte antigen-DQA_1,HLA-DQA_1)等位基因多态性的关系,寻找遵义地区部分ICP患者的HLA-DQA_1易感基因或保护基因,为ICP的预防及治疗提供一定的依据。方法对研究对象抽取静脉血,提取DNA,采用聚合酶链反应—序列特异性引物(PCR-SSP)法研究遵义地区20个ICP孕妇和10个正常孕妇的HLA-DQA_1等位基因的多态性。结果所有标本共检出11种HLA-DQA_1基因表型,ICP患者HLA-DQA_1*0302基因频率高于正常孕妇(34.21%与15.79%),但二者差异无显著性(P＞0.05)。结论HLA-DQA_1等位基因可能与遵义地区部分ICP患者的发病无明显关联性。
Objective To investigate the relationship between human leucocyte antigen -DQA_1 Polymorphism distribution in intrahepatic cholestasis of pregnancy in zun yi district.Methods The HLA-DQA_1 typing were analysed in blood samples using polymerase chain reaction with sequence-specific primer(PCR-SSP)in twenty patients and ten healthy pregnant women.Results Eleven types of HLA-DQA_1 alleles were detected. Frequency of HLA-DQA_1 * 0302 in ICP is more than healthy pregancy(34.21%,15.79 %),but the analysis showed no statistically significant difference between the two groups (P＞0.05).Conclusion It is unlikely that an HLA-DQA_1 allele is primarily associated with susceptibility or resistance to ICP in Zunyi district.
Objective To investigate the relationship between human leucocyte antigen -DQA_1 Polymorphism distribution in intrahepatic cholestasis of pregnancy in zun yi district.Methods The HLA-DQA_1 typing were analysed in blood samples using polymerase chain reaction with sequence-specific primer(PCR-SSP)in twenty patients and ten healthy pregnant women.Results Eleven types of HLA-DQA_1 alleles were detected. Frequency of HLA-DQA_1 * 0302 in ICP is more than healthy pregancy(34.21%,15.79 %),but the analysis showed no statistically significant difference between the two groups (P＞0.05).Conclusion It is unlikely that an HLA-DQA_1 allele is primarily associated with susceptibility or resistance to ICP in Zunyi district.
引文
[1]章崇娟,主编.医学免疫学纲要.四川:四川大学出版社,2007:54-56
[2]乐杰,主编.妇产科学.第六版.北京:人民卫生出版社,2004:107-108
[3]Savander M,Ropponen A,Avela K,et al.Genetic evidence of beterogeeity in intrahatic choiestasis of pregnecy.Gut.2003;52(7):1025-1029
[4]Lammert F,Marsehall H U,GlantzA,et al.Intrahepaticcholestasis of pregnancy:molecul arpathogenesis,diagnosis and management.JHepatol 2000,33(6):1012-1021
[5]Scheuer P,Chambers J,Rogers A.Intrahepatic cholestasis of pregnancy.Br Med J,1995,310(1):260
[6]龚非力,主编.医学免疫学.第二版.北京:科学出版社,2003:118-134
[7]曾常茜,张逢春主编.医学免疫学.北京:人民军医出版社,2006:106
[8]Reyes H,WegnannME,SegoviaN,et al HLA in Chileans with intrahepatie cholestasis of pregnancy.Hepatology,1982;2:463-466
[9]周小玲,曹来英,魏敏.妊娠肝内胆汁淤积的病因学研究进展.国外医学妇幼保健分册,2004:15(3):167-169
[10]陈富强,范丽安,许铃娣,等.HLA-DQBI等位基因与妊娠肝内胆汁淤积症的相关性研究.中华围产医学杂志,2003:6(1):39-40
[11]彭兵,刘淑芸,王晓东,等.人类白细胞抗原G、E与肝内胆汁淤积症的相关性研究.四川大学学报(医学版)2007;38(5)776-782
[12]彭冰,陈强,张力,等.成都地区妊娠期肝内胆汁淤积症与人类白细胞抗原-DQA_1的相关性研究.中华医学遗传学杂志,2006:5(23):555-557
[13]李玲,胡琼,郑艺,等.HLA-DQA。等位基因与妊娠期肝内胆汁淤积症的相关性研究.中国妇幼保健,2008:23(34):4904-4905
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[14]彭冰,刘淑芸.辅助性T淋巴细胞亚型与妊娠期肝内胆汁淤积症发病的关系.中华妇产科杂志,2002,37(9):516-518.
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[16]刘义明,高卉,莫伟.乙型肝炎病毒感染与妊娠期肝内胆汁淤积症相关性的探讨.中国热带医学,2008,8(9):1547.
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[22]Savander M,Ropponen A,Avela K,et al.Genetic evidence of heterogeneity in intrahepatic eholestasis of pregnancy.Gut,2003,52(7):1025-1029.
[23]刘玉凌,乔福元,刘海意,等.妊娠肝内胆汁淤积症患者MDR3基因突变的研究.中华妇产科杂志,2006,41(4):266-267.
[24]宫磊,朱延玲,胡卫华,等.ABCB4基因外显子12和23突变与妊娠期肝内胆汁淤积症的关系实用医学杂志 2007,23(12):1782.
[25]Van Mil SW,Van Ort MM,Van den Berg IE.et al.FIC1 is expressed at apical membranes of different epithelial cells in the digestive tract and is induced in the small intestine during po- stnatal development of mice.Pediatr Res,2004;56(6):981-987.
[26]Harris M J,Arias M.FIC1,a P-type ATPase linked cholestatic liver disease,has homo logues(ATPSB2 and ATP8B3)express throughout the body.Biochimica et Biophysica A eta,2003;1633(2):127-131.
[27]Mullenbach R,Bennett A,Tetlow N,et al.ATP8B1 mutations in British eases within trahepatic cholestasis of pregnancy.Gut,2005;54(6):829-834.
[28]Eloranta ML,Hldi T,Hiltunen M,et al.Association of single nucleotide polymorphisms of the bile salt export pump gene with intrahepatic cholestasis of pregnancy.Scand J Gastroenterol,2003,38(6):648-652.
[29]Pauli-Magnus C,Lang T,Meier Y,et al.Sequence analysis of bile salt export pump(ABCB11)and multidrug resistance pglycoprotein 3(ABCB4,MDR3)in patients with intrahepatic cholestasis of pregnaney.Pharmacogenetics,2004,14(2):91-102.
[30]Meier Y,Zodan T,Lang C,et al.Increased susceptibility for intra-hepatie cholestasis of pregnancy and contraceptive-induced cholestasis in carders of the polymorphism in the bile salt export pump.World J Gastroenterol,2008,14(1):38-45.
[31]Stieger B,Meier Y,Meier PJ.The bile salt export pump.Pflugers Arch,2007,453(5):611-620.
[32]Reyes H,Wegnarm ME,Segovia N,et al.HLA in Chileans with intrahepatic cholestasis of pregnancy.Hepatology,1982;2:463-466.
[33]周小玲,曹来英,魏敏.妊娠肝内胆汁淤积的病因学研究进展.国外医学妇幼保健分册,2004;15(3):167-169.
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[35]彭冰,陈强,张力,等.成都地区妊娠期肝内胆汁淤积症与人类白细胞抗原-DQA_1的相关性研究.中华医学遗传学杂志,2006;5(23):555-557.
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[2]乐杰,主编.妇产科学.第六版.北京:人民卫生出版社,2004:107-108
[3]Savander M,Ropponen A,Avela K,et al.Genetic evidence of beterogeeity in intrahatic choiestasis of pregnecy.Gut.2003;52(7):1025-1029
[4]Lammert F,Marsehall H U,GlantzA,et al.Intrahepaticcholestasis of pregnancy:molecul arpathogenesis,diagnosis and management.JHepatol 2000,33(6):1012-1021
[5]Scheuer P,Chambers J,Rogers A.Intrahepatic cholestasis of pregnancy.Br Med J,1995,310(1):260
[6]龚非力,主编.医学免疫学.第二版.北京:科学出版社,2003:118-134
[7]曾常茜,张逢春主编.医学免疫学.北京:人民军医出版社,2006:106
[8]Reyes H,WegnannME,SegoviaN,et al HLA in Chileans with intrahepatie cholestasis of pregnancy.Hepatology,1982;2:463-466
[9]周小玲,曹来英,魏敏.妊娠肝内胆汁淤积的病因学研究进展.国外医学妇幼保健分册,2004:15(3):167-169
[10]陈富强,范丽安,许铃娣,等.HLA-DQBI等位基因与妊娠肝内胆汁淤积症的相关性研究.中华围产医学杂志,2003:6(1):39-40
[11]彭兵,刘淑芸,王晓东,等.人类白细胞抗原G、E与肝内胆汁淤积症的相关性研究.四川大学学报(医学版)2007;38(5)776-782
[12]彭冰,陈强,张力,等.成都地区妊娠期肝内胆汁淤积症与人类白细胞抗原-DQA_1的相关性研究.中华医学遗传学杂志,2006:5(23):555-557
[13]李玲,胡琼,郑艺,等.HLA-DQA。等位基因与妊娠期肝内胆汁淤积症的相关性研究.中国妇幼保健,2008:23(34):4904-4905
[1]Lammert F,Marschall HU,Glantz A,etal.Intrahepatic cholestasis of pregnancy:molecular pathogenesis,diagnosis and management.Hepatol 2000,33(6):1012-1021
[2]Scheuer P,Chambers J,Rogers A.Intrahepatic cholestasis of pregnancy.Br Med,1995,310(1):260
[3]王琼,郑文东,郑文南,等.妊娠期肝内胆汁淤积症的病因及发病机制研究进展.中国医学文摘.计划生育和妇产科学,2004,1:73-75
[4]Leslie KK,Reznikov L,Simon FR,et al.Estrogens in intrahepatie eholestasis of pregnaney.Obstet Gynecol,2000,95(3):372-376
[5]李健伟,刘建.雌激素与妊娠期肝内胆汁淤积症发病关系的研究进展.国际检验医学杂志,2006,27(6):508.
[6]古航,胡电.妊娠期肝内胆汁淤积症.中华妇产科杂志 2003,38(2):121
[7]Pineda G,Aguayo J,Ribalta J,et al.Thyroid function tests in normal pregnant women(third trimester)and in pregnant women with intrahepatic cholestasis of pregnancy or with acute hepatitis.Rev MedChil,2000,128(1):35-43.
[8]Elferink RO,Groen AK.Genetic defects in hepatobiliary transport.Bioehim B iophys Acta,2002,1586(2):129-145
[9]Millkiewicz P,Elias E,Williamson C,et al.Obstetric Cholestasis.BMJ,2002,324(7330):123-124.
[10]Savande M,Ropponen A,Avela K,et al.Genetic evidence of heterogeneity in intrahepatic cholestasis of pregnancy.Gut,2003,52(7):1025-1029.
[11]何凤芝,曹恒萍.控制胆固醇饮食减少妊娠期肝内胆汁淤积症 2004,7:.2172.
[12]Wang Z,Dong M,Chu H,et al.Inereased serum levels of neopterin and soluble interleukin-2 receptor in intrahepatic cholestasis of pregnancy.Acta Obstet Gynecol Stand,2004,83(11):1067-1070.
[13]袁佩,虞斌,王秋伟,等.妊娠期肝内胆汁淤积症患者淋巴细胞亚群分析.江苏大学学报·医学版,2004,14(1):49-50.
[14]彭冰,刘淑芸.辅助性T淋巴细胞亚型与妊娠期肝内胆汁淤积症发病的关系.中华妇产科杂志,2002,37(9):516-518.
[15]丁依玲,谭辉,王丽琼.乙型肝炎病毒感染与妊娠肝内胆汁淤积症的相关性研究.中国实用妇科与产科杂志,2004,20(1):33.
[16]刘义明,高卉,莫伟.乙型肝炎病毒感染与妊娠期肝内胆汁淤积症相关性的探讨.中国热带医学,2008,8(9):1547.
[17]李小明,董春娥.妊娠期无症状乙型肝炎病毒携带者肝内胆汁淤积症的研究.国际医药卫生导报,2008,14(8):35.
[18]Oude Elferink R P,Paulusma C.Function and pathophysiologieal importance of ABCB4(MDR3 Pglyeoprotein) Pflugers Arch,2007,453(5):601-610.
[19]Jacquemin E,Cresteil D,Manouvrier S,et al.Heterozygous nonsense mutation of the MDR3 gene in familial intrahepatie cholestasis of pregnancy Lancet,1999,353(9148):210-211.
[20]Gendrot C,Bacq Y,Brechot MC,et al.A second heterozygous MDR3 nonsense mutation associated with intrahepatic cholestasis of pregnancy.J Med Genet,2003,40:32.
[21]Mullenbaeh R,Linton K J,Wiltshire S,et al.ABCB4 gene sequence variation in women with intrahepatie eholestasis of pregnancy.Med Genet,2003,40(5):70.
[22]Savander M,Ropponen A,Avela K,et al.Genetic evidence of heterogeneity in intrahepatic eholestasis of pregnancy.Gut,2003,52(7):1025-1029.
[23]刘玉凌,乔福元,刘海意,等.妊娠肝内胆汁淤积症患者MDR3基因突变的研究.中华妇产科杂志,2006,41(4):266-267.
[24]宫磊,朱延玲,胡卫华,等.ABCB4基因外显子12和23突变与妊娠期肝内胆汁淤积症的关系实用医学杂志 2007,23(12):1782.
[25]Van Mil SW,Van Ort MM,Van den Berg IE.et al.FIC1 is expressed at apical membranes of different epithelial cells in the digestive tract and is induced in the small intestine during po- stnatal development of mice.Pediatr Res,2004;56(6):981-987.
[26]Harris M J,Arias M.FIC1,a P-type ATPase linked cholestatic liver disease,has homo logues(ATPSB2 and ATP8B3)express throughout the body.Biochimica et Biophysica A eta,2003;1633(2):127-131.
[27]Mullenbach R,Bennett A,Tetlow N,et al.ATP8B1 mutations in British eases within trahepatic cholestasis of pregnancy.Gut,2005;54(6):829-834.
[28]Eloranta ML,Hldi T,Hiltunen M,et al.Association of single nucleotide polymorphisms of the bile salt export pump gene with intrahepatic cholestasis of pregnancy.Scand J Gastroenterol,2003,38(6):648-652.
[29]Pauli-Magnus C,Lang T,Meier Y,et al.Sequence analysis of bile salt export pump(ABCB11)and multidrug resistance pglycoprotein 3(ABCB4,MDR3)in patients with intrahepatic cholestasis of pregnaney.Pharmacogenetics,2004,14(2):91-102.
[30]Meier Y,Zodan T,Lang C,et al.Increased susceptibility for intra-hepatie cholestasis of pregnancy and contraceptive-induced cholestasis in carders of the polymorphism in the bile salt export pump.World J Gastroenterol,2008,14(1):38-45.
[31]Stieger B,Meier Y,Meier PJ.The bile salt export pump.Pflugers Arch,2007,453(5):611-620.
[32]Reyes H,Wegnarm ME,Segovia N,et al.HLA in Chileans with intrahepatic cholestasis of pregnancy.Hepatology,1982;2:463-466.
[33]周小玲,曹来英,魏敏.妊娠肝内胆汁淤积的病因学研究进展.国外医学妇幼保健分册,2004;15(3):167-169.
[34]陈富强,范丽安,许铃娣,等.HLA-DQB_1等位基因与妊娠肝内胆汁淤积症的相关性研究.中华围产医学杂志,2003;6(1):39-40.
[35]彭冰,陈强,张力,等.成都地区妊娠期肝内胆汁淤积症与人类白细胞抗原-DQA_1的相关性研究.中华医学遗传学杂志,2006;5(23):555-557.
[36]彭冰,刘淑芸,王晓东,等.人类白细胞抗原G、E与妊娠期肝内胆汁淤积症的相关性研究.四川大学学报(医学版),2007;38(5)779-782.
[37]Leclercq IA,Farrell GC,Schriemer R,et al.Leptin is essential for the hepatic fibrogenic response to chronic liver injury.J Hepatol,2002,37(2):206-213.
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