云南汉族多形性日光疹HLA-DQB1、DPB1等位基因相关性研究
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摘要
目的:探讨多形性日光疹(PLE)与HLA-DQB1、DPB1等位基因的关系,拟明确HLA-DQB1、DPB1基因在PLE发病机制中的作用。
方法:采用经典酚-氯仿从38例PLE患者和45例健康人外周静脉血白细胞提取基因组DNA,应用聚合酶链反应-直接测序(PCR-SBT)的方法对PLE患者和健康对照组进行HLA-DQB1、DPB1等位基因的检测。
结果:38例PLE患者和45例正常对照组PCR产物测序结果均可在最新的HLA-DQB1、DPB1等位基因序列中匹配到相应基因型,它们频率、相对危险率统计学分析结果表明,PLE患者组HLA-DQB1*050301等位基因频率较正常人对照组明显增高,差异有显著性(x~2=5.691,P＜0.05),其余均无统计学意义。
结论:推测HLA-DQB1*050301可能是云南汉族PLE的易感基因或与实际的易感基因连锁,未发现PLE患者HLA-DPB1的易感或保护基因,HLA-DPB1可能与PLE发病无关。
objective To explore the relationship between the allele of HLA-DQB1、DPB1 and polymorphous light eruption of the Han Nationality in Yunnan.
Method:Classical phenol-chloroform method was applied to extract DNA from vein blood of 38 PLE patients and 45 healthy people,then PCR-SBT was used to examine the HLA-DQB1、DPB1 allele gene of the people mentioned above.
Result:All sequence results of PCR product of 38 PLE patients and 45 control can be find the relevant gene type in the latest HLA-DQB1、DPB1 sequence.Statistics of their frequency,relative risk frequency indicate that the frequency of HLA-DQB1*050301 in PLE is higher than in control,and diversity is remarkable(x~2=5.691,P＜0.05),but the rest has no significance.
Conclusion:Inferring that HLA-DQB1*050301 may be the susceptible gene or linkage disequilibrium with the real susceptible gene of PLE of the Han Nationality in Yunnan.No susceptible gene or protective gene of HLA-DPB1 was discovered,and maybe that HLA- DPB1 has no association with PLE.
方法:采用经典酚-氯仿从38例PLE患者和45例健康人外周静脉血白细胞提取基因组DNA,应用聚合酶链反应-直接测序(PCR-SBT)的方法对PLE患者和健康对照组进行HLA-DQB1、DPB1等位基因的检测。
结果:38例PLE患者和45例正常对照组PCR产物测序结果均可在最新的HLA-DQB1、DPB1等位基因序列中匹配到相应基因型,它们频率、相对危险率统计学分析结果表明,PLE患者组HLA-DQB1*050301等位基因频率较正常人对照组明显增高,差异有显著性(x~2=5.691,P＜0.05),其余均无统计学意义。
结论:推测HLA-DQB1*050301可能是云南汉族PLE的易感基因或与实际的易感基因连锁,未发现PLE患者HLA-DPB1的易感或保护基因,HLA-DPB1可能与PLE发病无关。
objective To explore the relationship between the allele of HLA-DQB1、DPB1 and polymorphous light eruption of the Han Nationality in Yunnan.
Method:Classical phenol-chloroform method was applied to extract DNA from vein blood of 38 PLE patients and 45 healthy people,then PCR-SBT was used to examine the HLA-DQB1、DPB1 allele gene of the people mentioned above.
Result:All sequence results of PCR product of 38 PLE patients and 45 control can be find the relevant gene type in the latest HLA-DQB1、DPB1 sequence.Statistics of their frequency,relative risk frequency indicate that the frequency of HLA-DQB1*050301 in PLE is higher than in control,and diversity is remarkable(x~2=5.691,P＜0.05),but the rest has no significance.
Conclusion:Inferring that HLA-DQB1*050301 may be the susceptible gene or linkage disequilibrium with the real susceptible gene of PLE of the Han Nationality in Yunnan.No susceptible gene or protective gene of HLA-DPB1 was discovered,and maybe that HLA- DPB1 has no association with PLE.
引文
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2.Morison WL,Stern RS.Polymorphous light eruption:a common reaction uncommonly recognized.Acta Derm Venereol(Stockholm) 1982;62:237-240.
3.Ros AM,Wennersten G.Current aspects of polymorphous light eruption in Sweden.Photodermatology 1986;3:298-302.
4.Jansen CT.The natural history of polymorphous light eruptions.Arch Dermatol 1979;115:165-169.
5.Norris PG,Hawk JLM.The idiopathic photodermatoses:polymorphiclight eruption,actinic prurigo and hydroa vacciniforme.in:Hawk JLM,ed.Photodermatology.London:Arnold,1999;178-190.
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7.Khoo SW,Tay YK,Tham SN.Photodermatoses in a Singapore skin referral center.Clin Exp Dermatol 1996;21:263-268.
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9.邓丹琪,韩云涛,陈浩等.云南省不同地区多形性日光疹、慢性光线性皮炎患病率调查[J].中华皮肤科杂志,2005;38(7):451-452.
10.Epstein S.Studies in abnormal human sensitivity to light.Ⅳ.Photoallergic concept of prurigo aestivalis.J Invest Dermatol 1942;5:289-298.
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13.McFadden JP,Norris PG,Cerio R,et al.Heat shock protein 65 immunoreactivity in experimentally induced polymorphic light eruption.Acta Derm Venereol 1994;74:283-285.
14.Herbert H(o|¨)nigsmann.Polymorphous light eruption Photodermatology,Photoimmunology &Photomedicine 24;155-161.
15.Bansal I,Kerr H,Janiga JJ,et al.Pinpoint papular variant of polymorphous light eruption:clinical and pathological correlation.J Eur Acad Dermatol Venereol.2006 Apr;20(4):406-10.
16.Van Praag MC,Boom BW,Vermeer BJ.Diagnosis and treatment of polymorphous light eruption.Int J Dermatol 1994;33:233-239.
17.K(o|¨)lgen W,Van Weelden H,Den Hengst S,et al.CD11b1 cells and ultraviolet-B-resistant CDlal cells in skin of patients with polymorphous light eruption.J Invest Dermatol 1999;113:4-10.
18.K(o|¨)lgen W,van Meurs M,Jongsma M,et al.Differential expression of cytokines in UV-B-exposed skin of patients with polymorphous light eruption:correlation with Langerhans cell migration and immunosuppression.Arch Dermatol 2004;140:295-302.
19.S.Lembo,J.Fallon,P.O'Kelly and G.M.Murphy Polymorphic light eruption and skin cancer prevalence:is one protective against the other? British Journal of Dermatology 2008.159,pp1342-1347.
20.农祥、何黎.昆明山海棠抗接触变应性光皮炎的研究[J].中华皮肤科杂志,2004;37(10):592-594.
21.舒虹,何黎.复方昆明山海棠颗粒剂治疗豚鼠光变应性接触性皮炎的药效学研究[J].中国皮肤性病学杂志,2007;21(10):586-589.
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24.Bataille V,MacGregor A,McGregor JM,et al.The heritability of Photosensitivity in monozygous and dizygous twins.Br J Dermatol,1998,;138(4):734.
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28.范丽安,周光炎.人类基因组MHC测序及其免疫学意义,上海免疫学杂志1999;19(6):321-323.
29.陈慰峰.医学免疫学[M].人民卫生出版社.
30.Schreuder G M,Hurley C K,Marsh S G,et al.HLA Dictionary2004:Summary of HLA-A,-B,-C,-DRB 1/3/4/5-DQB1 A12 leles and Their Association wit h Serologically DefmedHLA-A,-B --C,-DR,and-DQ Antigens[J].Hum Immunol,2005;66(2):170-210.
31.Nishimaki K,Kawamura T,Inada H,et al.HLA DPB 1 3 0201 gene confers disease susceptibility in japanese with childhood onset type Ⅰ diabetes independent of HLA2DR and DQ genotypes.Diabetes Res Clin Pract,2000;47(1):49-55.
32.Wang Z,White PS,Petrovic M,et al.Differential susceptibilities to chronic beryllium disease contributed by different GLU69 HLA2DPB1 and DPA1 alleles.J Immunol,1999;163(3):1647-1653.
33.张雄鹰,秦雄伟.山西汉族类风湿关节炎与HLA-DPB1基因相关性研究初探长治医学院学报.2008;22(1)24-25.
34.单岩东 张昆南 视神经脊髓炎患者HLA-DPB1等位基因多态性的研究 实用临床医学2008,9(5):11-12.
35.谭建明,周永昌,唐孝达.组织配型技术与临床应用[M].JE京:人民卫生出版社.2002;363-366.
36.Petersdorf EW.HLA matching jn allogeneic stem celI transplantation.Curr Opin Hematol 2004;11(6):386-391.
37.Adms SD,Barracchini KC,Simonis TB,et al.High thoughput HLA seqence based typing (SBT) utilizing the ABI PRISM 3700 DNA Analyzer[J].Tumori,2001,87(2):40-43.
38.Rozemuller EH,van der Zwam AW,Voorter CE,et al.DPB1~*8501,a novel DPB1 variant in the US Black poulation[J],Tissue Antigens,2000,56(3):282-284.
39.郝桂琴,肖露露.分子生物学技术在HLA分型中的应用[J]。中国实验血液学杂志,2002;10(3)268-272.
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42.Grabczynska SA,McGregor JM,Kondeatis E,et al.Actinic prurigo and polymorphic light eruption:common pathogenesis and the importance of HLA-DR4/DRB1~*0407.Br J Dermatol.1999 Feb;140(2):232-236.
1 Millard TP,Bataille V,Snieder H,et al.The heritability of polymorphic light eruption.J Invest Dermato12000;115(3):467-470.
2 胡卫红.博士研究生学位论文,云南五个少数民族HLA-DPB1基因多态性的研究,云大生命科学院,2005.
3 Ramal LM,L(?)pez-Nevot MA,Sabio JM,et al.Systemic lupus erythematosus in southern Spain:a comparative clinical and genetic study between Caucasian and Gypsy patients.Lupus.2004;13(12):934-40.
4 Shankarkumar U,Ghosh K,Badakere SS,et al.HLA-DRB1~*03 and DQB1~*0302associations in a subset of patients severely affected with systemic lupus erythematosus from western India.Ann Rheum Dis.2003 Jan;62(1):92-93.
5 Chan MT,Owen P,Dunphy J et al.Associations of erosive arthritis with anti-cyclic citrullinated peptide antibodies and MHC Class Ⅱ alleles in systemic lupus erythematosus.J Rheumatol.2008;35(1):77-83.
6 Grabczynska SA,McGregor JM,Kondeatis E,et al.Actinic prurigo and polymorphic light eruption:common pathogenesis and the importance of HLA-DR4/DRB1~*0407.Br J Dermatol.1999 Feb;140(2):232-6.
7 Lee E,Lendas KA,Chow S,et al.Disease relevant HLA class Ⅱ alleles isolated by genotypic,haplotypic,and sequence analysis in North American Caucasians with pemphigus vulgaris.Hum Immunol,2006;67(12):125-139.
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9 单岩东,张昆南.视神经脊髓炎患者HLA-DPB1等位基因多态性的研究.实用临床医学2008;9(5):11-12.
10 张雄鹰,秦雄伟.山西汉族类风湿关节炎与HLA-DPB1基因相关性研究初探.长治医学院学报 2008;22(1)24-25.
1.Lie BA,Thorsby E.Several genes in the extended human MHC contribute to predisposition to antoimmune diseases.Current Opinion in Immunology,2005,17:526-531.
2.Beck S,TrowsdaleJ.The human major histocom-patibility complex:lessons from the DNA sequence.Annu Rev Genomics Hum Genet 2000,1:117-37.htrp://www-inimuno.pathxam.ac.uk/～in3muno/mhc/mhc.html.
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13.Chan MT,Owen P,Dunphy J et al.Associations of erosive arthritis with anti-cyclic citrullinated peptide antibodies and MHC Class Ⅱ alleles in systemic lupus erythematosus.J Rheumatol.2008,35(1):77-83
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16.Miyagawa S,Niizeki H,Yamashina Y,et al.Genotyping for HLA-A,B and C alleles in Japanese patients with pemphigus:prevalence of Asian alleles of the HLA-B15 family.Br J Dermatol,2002,146(1):52-58.
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18.Lee E,Lendas KA,Chow S,et al.Disease relevant HLA class Ⅱ alleles isolated by genotypic,haplotypic,and sequence analysis in North American Caucasians with pemphigus vulgaris.Hum Immunol,2006,67(12):125-139
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24.Bansal I,Kerr H,Janiga JJ,et al.Pinpoint papular variant of polymorphous light eruption:clinical and pathological correlation.J Eur Acad Dermatol Venereol.2006Apr;20(4):406-10.
25.Grabczynska SA,McGregor JM,Kondeatis E,et al.Actinic prurigo and polymorphic light eruption:common pathogenesis and the importance of HLA-DR4/DRB 1*0407.Br J Dermatol.1999 Feb;140(2):232-6.
2.Morison WL,Stern RS.Polymorphous light eruption:a common reaction uncommonly recognized.Acta Derm Venereol(Stockholm) 1982;62:237-240.
3.Ros AM,Wennersten G.Current aspects of polymorphous light eruption in Sweden.Photodermatology 1986;3:298-302.
4.Jansen CT.The natural history of polymorphous light eruptions.Arch Dermatol 1979;115:165-169.
5.Norris PG,Hawk JLM.The idiopathic photodermatoses:polymorphiclight eruption,actinic prurigo and hydroa vacciniforme.in:Hawk JLM,ed.Photodermatology.London:Arnold,1999;178-190.
6.Pao C,Norris PG,Corbett M,et al.Poly morphic light eruption:prevalence in Australia and England[J].Br J Dermatol 1994;130:62-64.
7.Khoo SW,Tay YK,Tham SN.Photodermatoses in a Singapore skin referral center.Clin Exp Dermatol 1996;21:263-268.
8.赵辨.临床皮肤病学[M].南京,江苏科学技术出版社,2001;585-587.
9.邓丹琪,韩云涛,陈浩等.云南省不同地区多形性日光疹、慢性光线性皮炎患病率调查[J].中华皮肤科杂志,2005;38(7):451-452.
10.Epstein S.Studies in abnormal human sensitivity to light.Ⅳ.Photoallergic concept of prurigo aestivalis.J Invest Dermatol 1942;5:289-298.
11.Norris PG,Morris J,McGibbon DM,et al.Polymorphic light eruption:an immunopathological study of evolving lesions.Br JDermatol 1989;120:173-183.
12.Norris PG,Barker JNWN,Allen M,et al.Adhesion molecule expression in polymorphic light eruption.J Invest Dermatol 1992;99:504-508.
13.McFadden JP,Norris PG,Cerio R,et al.Heat shock protein 65 immunoreactivity in experimentally induced polymorphic light eruption.Acta Derm Venereol 1994;74:283-285.
14.Herbert H(o|¨)nigsmann.Polymorphous light eruption Photodermatology,Photoimmunology &Photomedicine 24;155-161.
15.Bansal I,Kerr H,Janiga JJ,et al.Pinpoint papular variant of polymorphous light eruption:clinical and pathological correlation.J Eur Acad Dermatol Venereol.2006 Apr;20(4):406-10.
16.Van Praag MC,Boom BW,Vermeer BJ.Diagnosis and treatment of polymorphous light eruption.Int J Dermatol 1994;33:233-239.
17.K(o|¨)lgen W,Van Weelden H,Den Hengst S,et al.CD11b1 cells and ultraviolet-B-resistant CDlal cells in skin of patients with polymorphous light eruption.J Invest Dermatol 1999;113:4-10.
18.K(o|¨)lgen W,van Meurs M,Jongsma M,et al.Differential expression of cytokines in UV-B-exposed skin of patients with polymorphous light eruption:correlation with Langerhans cell migration and immunosuppression.Arch Dermatol 2004;140:295-302.
19.S.Lembo,J.Fallon,P.O'Kelly and G.M.Murphy Polymorphic light eruption and skin cancer prevalence:is one protective against the other? British Journal of Dermatology 2008.159,pp1342-1347.
20.农祥、何黎.昆明山海棠抗接触变应性光皮炎的研究[J].中华皮肤科杂志,2004;37(10):592-594.
21.舒虹,何黎.复方昆明山海棠颗粒剂治疗豚鼠光变应性接触性皮炎的药效学研究[J].中国皮肤性病学杂志,2007;21(10):586-589.
22.Millard TP,Bataille V,Snieder H,et al.The heritability of polyrnorphic light eruption.J Invest Dermatol,2000;115(3):467-470.
23.McGregor JM,Grabczynska S,Vaughan R,et al.Genetic modeling of abnormal photosensitivity in families with polymorphic light eruption and actinic prurigo.J Invest Dermatol,2000;115(3):471-476.
24.Bataille V,MacGregor A,McGregor JM,et al.The heritability of Photosensitivity in monozygous and dizygous twins.Br J Dermatol,1998,;138(4):734.
25.赵辨.临床皮肤病学[M].南京,江苏科学技术出版社.
26.Lie BA,Thorsby E.Several genes in the extended human MHC contribute to predisposition to antoimmune diseases.Current Opinion in Immunology,2005;17:526-531.
27.Beck S,TrowsdaleJ.The human major histocom-patibility complex:lessons from the DNA sequence.AnnuRevGenomicsHumGenet2000;1:117-37.http://www-immuno.path.cam.ac.uk/-immuno/mhc/mhc.html.
28.范丽安,周光炎.人类基因组MHC测序及其免疫学意义,上海免疫学杂志1999;19(6):321-323.
29.陈慰峰.医学免疫学[M].人民卫生出版社.
30.Schreuder G M,Hurley C K,Marsh S G,et al.HLA Dictionary2004:Summary of HLA-A,-B,-C,-DRB 1/3/4/5-DQB1 A12 leles and Their Association wit h Serologically DefmedHLA-A,-B --C,-DR,and-DQ Antigens[J].Hum Immunol,2005;66(2):170-210.
31.Nishimaki K,Kawamura T,Inada H,et al.HLA DPB 1 3 0201 gene confers disease susceptibility in japanese with childhood onset type Ⅰ diabetes independent of HLA2DR and DQ genotypes.Diabetes Res Clin Pract,2000;47(1):49-55.
32.Wang Z,White PS,Petrovic M,et al.Differential susceptibilities to chronic beryllium disease contributed by different GLU69 HLA2DPB1 and DPA1 alleles.J Immunol,1999;163(3):1647-1653.
33.张雄鹰,秦雄伟.山西汉族类风湿关节炎与HLA-DPB1基因相关性研究初探长治医学院学报.2008;22(1)24-25.
34.单岩东 张昆南 视神经脊髓炎患者HLA-DPB1等位基因多态性的研究 实用临床医学2008,9(5):11-12.
35.谭建明,周永昌,唐孝达.组织配型技术与临床应用[M].JE京:人民卫生出版社.2002;363-366.
36.Petersdorf EW.HLA matching jn allogeneic stem celI transplantation.Curr Opin Hematol 2004;11(6):386-391.
37.Adms SD,Barracchini KC,Simonis TB,et al.High thoughput HLA seqence based typing (SBT) utilizing the ABI PRISM 3700 DNA Analyzer[J].Tumori,2001,87(2):40-43.
38.Rozemuller EH,van der Zwam AW,Voorter CE,et al.DPB1~*8501,a novel DPB1 variant in the US Black poulation[J],Tissue Antigens,2000,56(3):282-284.
39.郝桂琴,肖露露.分子生物学技术在HLA分型中的应用[J]。中国实验血液学杂志,2002;10(3)268-272.
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