广西汉族狼疮性肾炎与HLA-DQA1等位基因相关性研究
摘要
目的:探讨广西地区汉族系统性红斑狼疮( Systemic lupus erythematosus, SLE)患者与HLA-DQA1等位基因的相关性。
方法:用聚合酶链式反应-序列特异性引物(PCR-SSP)法对64例广西汉族SLE患者及60例汉族健康人群的HLA-DQA1频率进行检测。
结果:1.用12对DQA1引物检出HLA-DQA1*0101、0102、0103、0104、0201、0301、0302、0401、0501、0601共10个亚型;SLE组HLA-DQA1*0101、0102等位基因频率较正常对照组显著升高(χ2 =8.627 , P=0.003,RR=3.421及χ2=8.965,P=0.003,RR=3.314);狼疮性肾炎(Lupus nephritis,LN)组HLA-DQA1*0102等位基因频率较无LN表现的SLE组显著升高(χ2 =6.418 , P=0.011,RR=4.688);LN组HLA-DQA1*0501等位基因频率较无LN表现的SLE组显著降低(χ2 =6.130 , P=0.013,RR=0.172);未发现与LN病理类型显著相关的HLA-DQA1等位基因。
结论:DQA1*0101、0102可能是广西汉族SLE的易感基因;DQA1*0101可能是广西汉族LN的易感基因,HLA-DQA1*0501可能是广西汉族LN的保护基因;未发现与LN病理类型显著相关的HLA-DQA1等位基因。
Objective: To explore the association of HLA-DQA1 alleles with Systemic lupus erythematosus of Han nationality in Guangxi.
Methods:Polymerase chain reaction-sequence specific primers technique(PCR-SSP)was used to comparatively study the allelic genes in HLA-DQA1 locus in 64 patients with SLE and 60 selected unrelated healthy controls of Han subjects.
Results: Twelve pairs primers amplified out 10 isoforms within HLA-DQA1 region:HLA-DQA1*0101、0102、0103、0104、0201、0301、0302、0401、0501、0601。The allelic frequencies of HLA-DQA1*0101、0102 was significantly increased in SLE patients than those of the controls(χ2=8.627,P=0.003 ,RR=3.421;χ2=8.965,P=0.003 ,RR=3.314); The allelic frequencies of HLA-DQA1*0102 was significantly increased in LN patients than those of the non-LN SLE patients(χ2 =6.418 , P=0.011, RR=4.688),but the allelic frequencies of HLA-DQA1*0501 was significantly decreased in LN patients than those of the non-LN SLE patients(χ2 =6.130 , P=0.013,RR=0.172);We have no found the association of HLA-DQA1 alleles with the renal pathologic of LN.
Conclusion:The HLA-DQA1*0101、0102 allele may be susceptible gene for SLE in Guangxi Han nationality.The HLA-DQA1*0101 may be susceptible gene for LN in Guangxi Han Nationality. The HLA-DQA1*0501 may be protecting gene for LN in Guangxi Han Nationality. We have no found the association of HLA-DQA1 alleles with the pathologic of LN.
方法:用聚合酶链式反应-序列特异性引物(PCR-SSP)法对64例广西汉族SLE患者及60例汉族健康人群的HLA-DQA1频率进行检测。
结果:1.用12对DQA1引物检出HLA-DQA1*0101、0102、0103、0104、0201、0301、0302、0401、0501、0601共10个亚型;SLE组HLA-DQA1*0101、0102等位基因频率较正常对照组显著升高(χ2 =8.627 , P=0.003,RR=3.421及χ2=8.965,P=0.003,RR=3.314);狼疮性肾炎(Lupus nephritis,LN)组HLA-DQA1*0102等位基因频率较无LN表现的SLE组显著升高(χ2 =6.418 , P=0.011,RR=4.688);LN组HLA-DQA1*0501等位基因频率较无LN表现的SLE组显著降低(χ2 =6.130 , P=0.013,RR=0.172);未发现与LN病理类型显著相关的HLA-DQA1等位基因。
结论:DQA1*0101、0102可能是广西汉族SLE的易感基因;DQA1*0101可能是广西汉族LN的易感基因,HLA-DQA1*0501可能是广西汉族LN的保护基因;未发现与LN病理类型显著相关的HLA-DQA1等位基因。
Objective: To explore the association of HLA-DQA1 alleles with Systemic lupus erythematosus of Han nationality in Guangxi.
Methods:Polymerase chain reaction-sequence specific primers technique(PCR-SSP)was used to comparatively study the allelic genes in HLA-DQA1 locus in 64 patients with SLE and 60 selected unrelated healthy controls of Han subjects.
Results: Twelve pairs primers amplified out 10 isoforms within HLA-DQA1 region:HLA-DQA1*0101、0102、0103、0104、0201、0301、0302、0401、0501、0601。The allelic frequencies of HLA-DQA1*0101、0102 was significantly increased in SLE patients than those of the controls(χ2=8.627,P=0.003 ,RR=3.421;χ2=8.965,P=0.003 ,RR=3.314); The allelic frequencies of HLA-DQA1*0102 was significantly increased in LN patients than those of the non-LN SLE patients(χ2 =6.418 , P=0.011, RR=4.688),but the allelic frequencies of HLA-DQA1*0501 was significantly decreased in LN patients than those of the non-LN SLE patients(χ2 =6.130 , P=0.013,RR=0.172);We have no found the association of HLA-DQA1 alleles with the renal pathologic of LN.
Conclusion:The HLA-DQA1*0101、0102 allele may be susceptible gene for SLE in Guangxi Han nationality.The HLA-DQA1*0101 may be susceptible gene for LN in Guangxi Han Nationality. The HLA-DQA1*0501 may be protecting gene for LN in Guangxi Han Nationality. We have no found the association of HLA-DQA1 alleles with the pathologic of LN.
引文
1. Trowsdale J Major histocopatibility complex.Res-Immunol,1997,148(6):425-426.
2. 李晓岚,冒长峙,洪坤学,等.云南汉族系统性红斑狼疮与 HLA-DRB1、DQA1、DQB1 相关性研究.中华医学遗传学杂志,2001,18(5):408-409.
3. 李峰,冒长峙,邵剑春,等.云南白族系统性红斑狼疮与 HLA-DR、DQ 相 关性的研究.中华遗传学杂志,1999,16(6):612-413.
4. 李峰,冒长峙,邵剑春,等.云南白族系统性红斑狠疮患者 HLA-DR、DQ 多态性研究.中华皮肤科杂志,2000,33(1):33.
5. Martin-Villa JM, Martinez-laso J, Moreno - Pelayo MA, et al. Differential contribution of HLA-DR,DQ,and TAP2 allelesto systemic lupus erythematosus susceptibility in Spanish patients role of TAP2*01 alleles in Roautoantibody production.Ann Rheum Dis, 1998, 57(4):214-219.
6. Reveille JD,Moulds JM,Ahn C,et al.Systemic lupus erythe- matosus in three ethnic groups:The effects of HLA classⅡ,C4,and CR1 alleles,socioeconomic factors,and ethnicity at disease onset. Arthritis Rheum,1998,41(7):1161-1172.
7. 王敏,董怡,赵怡,等.人类白细胞抗原 DR 基因与狼疮性肾炎的相关性探讨.中华肾脏病杂志,1997,3(6):323-326.
8. 彭学标综述.HLA-Ⅱ类基因与系统性红斑狼疮易感性.国外医学皮肤性病学分册,1996,12:18-21.
9. 施为,刘稚然,谢红付. 系统性红斑狼疮患者 HLA-DQ 基因与自身抗体及肾脏受累的研究.中华皮肤科杂志,2001,34(3):222-223.
10. 熊平,杨颖,龚非力.一种新的 HLA-Ⅱ类基因分型方法----PCR-SSP 技术的建立.免疫学杂志,1996,12940:258-261.
11. Marsh SGE,Bodmer JG.HLA class region nucleotide sequences. TissueAntigens,1995,46:258-280.
12. 龙桂芳,阿卜迪,李卫,等.应用序列特异引物 PCR 法对广西壮族 HLA-DQA1 进行基因分型.中华血液学杂志,1995,16(10):532-534.
13. 刘栋华,梁伶,苏家光,等.广西地区壮族系统性红斑狼疮与 HLA-DQA1 等位基因的相关性研究.中国皮肤性病学杂志,2004,8(18):449-450.
14. Skarsvag S,Hansen KE,Holst, et al.Distribution of HLA class Ⅱalleles among Scandinavian patients with systemic lupus erythe- matosus. Scand J Immunol,1995,42(5):564-571
15. Yao Z,Kimura a,Hartung K et al. Polomorphism of HLA-DQA1 promoter region(QAP)and DRB1,QAP,DQA1,DQB1 haplotypes in SLE,SLE Study Group Members.Immunogenetics,1993,38(6):421-429.
16. 潘星华,陆建荣,猪子英俊,等.中国汉人 HLA-DQAl 基因对系统性红斑狼疮的遗传易感性研究.中国免疫学杂志,1995,11(1):19-22.
17. 查旭山,禤国维,陈红,等.广东籍汉人 HLA-DQA DQB 基因与 SLE 的易感性研究.中国皮肤性病学杂志,2004,2(7):86-87.
18. Marchini M,Antonioli R,Lleo A,et al.HLA class Ⅱ antigens associated with lupus nephritis in Intalian SLE patients.Hum Immunol,2003,64(4):462-468.
19. Azizah MR,Aninoi SS,Kuak SH et al.The association of the HLA class II antigens with clinical and autoantibody expression in Malaysian Chinese patients with systemic lupus erythematosus. Asian Pac J auergy Immunol,2001,19(2):93-100.
20. 谢尚葵、冯树芳、沈福民,等.系统性红斑狼疮临床表现与 HLA-Ⅱ类单倍型关联的研究.中华微生物和免疫学杂志,2000,20(1):66-69.
21. MorimotoS, HashimotoH, YamanakaK, etal. Multicenter cooperative study of HLA class Ⅱ alleles in Japanese patients with SLE, Morden Rheumatology,2000,22(2):71-76.
1 Trowsdale J. Major histocopatibility complex .Res-Immunol,1997,148(6):425-426.
2 曹孟德,秦东春,孙含笑..HLA 分子生物学及临床应用,郑州:河南医科大学出版社.1998:147-150.
3 李霞,朱运良. HLA 与自身免疫性疾病研究进展. 国外医学免疫学分册,1999,22(2):75-78.
4 周光严.主要组织相容性复合体和特异性免疫应答.中华消化内科杂志,1995,15(2):100-102.
5 Galeazzi M, Annunziata P, Sebastiani GD, et al. Anti-GM1 in a large cohort of European patient with SLE and HLA class Ⅱ gene associations. J Rheumatol. 2002,27(1):135-141.
6 Lee AH, Bateman AC, Tumer SJ, et al. HLA class Ⅱ DRB1 and DQB1 allelic polymorphism and sclerosing lymphocytic lobulitis of the breast. J Clin Pathol, 1999,52(6):445-449.
7 Skarsvag S,Hansen KE,Holst, et al.Distribution of HLA class Ⅱalleles among Scandinavian patients with systemic lupus erythematosus. Scand J Immunol,1995,42(5):564-571.
8 Reveille JD,Schrohenloher RE,Acton RT, et al.DNA analysis of HLA-DR and DQ genes in Americans blacks with systemic lupus erythematosus .Arthritis Rheum,1989,32(10):1243-1251.
9 Yao Z,Kimura a,Hartung K et al. Polomorphism of HLA-DQA1 promoter region(QAP)and DRB1,QAP,DQA1,DQB1 haplotypes in SLE,SLE Study Group Members.Immunogenetics,1993,38(6): 421-429.
10 Dong RP,Kimura A,Hashimoto H,et al.Difference in HLA linked genetic backgroud between MCTD and SLE.Tissue Antigens,1993,41(1):20-25.
11 Doherty DG,Ireland R,Demaine AG,et al.MHC and susceptibility to SLE in southern Chinese.Arthritis Rheum,1992,35(6):641-646.
12 De Juan,Maritin JM,Gomez Reino JJ,et al. Differential contribution of C4 and HLA-DQ genes to systemic lupus erythematosus susceptibility. Hum Genet,1993 ,91(6):579-584.
13 张咸宁,潘星华,朱定良,等.中国南方汉族人群 HLA-DQB1 基因对系统性红斑狼疮的易感性研究.中国免疫学杂志,1997,13(1):37-39.
14 郑文军,梁伶,苏家光,等.广西地区汉族系统性红斑狼疮与 HLA-DRB1 等位基因的相关性研究.广西医科大学学报,2004,21(3):336-338.
15 刘栋华,梁伶,苏家光,等. 广西地区壮族系统性红斑狼疮与HLA-DQA1等位基因的相关性研究.中国皮肤性病学杂志,2004,8(18):449-450.
16 曹秀菁,叶冬青,李向培,等.皖籍汉人 HLA-DQA1 基因型与 SLE 相关性研究.中国皮肤性病学杂志,2004,18(2):83-85.
17 Marchini M,Antonioli R,Lleo A,et al.HLA class Ⅱ antigens associated with lupus nephritis in Intalian SLE patients.Hum Immunol,2003,64(4):462-468.
18 Azizah MR,Aninoi SS,Kuak SH et al. The association of the HLA class II antigens with clinical and autoantibody expression inMalaysian Chinese patients with systemic lupus erythematosus.Asian Pac J auergy Immunol;2001,19(2):93-100.
19 MorimotoS, HashimotoH, YamanakaK, et al. Multicenter cooperative study of HLA class Ⅱ alleles in Japanese patients with SLE, Morden Rheumatology,2000,22(2):71-76.
20 Kim TG, Kim HY, Lee SH, et al. systemic lupus erythematosus with nephritis is strongly associated with the TNFB*2 hemozygote in Korean population.Hum Immunol,1996,46(1):10-17.
21 王敏,董怡,赵怡,等.人类白细胞抗原 DR 基因与狼疮性肾炎的相关性探讨.中华肾脏病杂志,1997,3(6):323-326.
22 谢尚葵,冯树芳,沈福民,等.系统性红斑狼疮临床表现与 HLA-Ⅱ类单倍型关联的研究.中华微生物和免疫学杂志,2000,20(1):66-69.
23 David Lawrence. The single nucleotide polymorphism of PCDG-1 in European patients with SLE. Lancet, 2002,320:1399-1405.
24 冯学兵,沈南,陈顺乐等. 中国人群 16 号染色体 q12 区存在系统性红斑狼疮易感基因.中华医学遗传学杂志,2003,20(1):27-30.
2. 李晓岚,冒长峙,洪坤学,等.云南汉族系统性红斑狼疮与 HLA-DRB1、DQA1、DQB1 相关性研究.中华医学遗传学杂志,2001,18(5):408-409.
3. 李峰,冒长峙,邵剑春,等.云南白族系统性红斑狼疮与 HLA-DR、DQ 相 关性的研究.中华遗传学杂志,1999,16(6):612-413.
4. 李峰,冒长峙,邵剑春,等.云南白族系统性红斑狠疮患者 HLA-DR、DQ 多态性研究.中华皮肤科杂志,2000,33(1):33.
5. Martin-Villa JM, Martinez-laso J, Moreno - Pelayo MA, et al. Differential contribution of HLA-DR,DQ,and TAP2 allelesto systemic lupus erythematosus susceptibility in Spanish patients role of TAP2*01 alleles in Roautoantibody production.Ann Rheum Dis, 1998, 57(4):214-219.
6. Reveille JD,Moulds JM,Ahn C,et al.Systemic lupus erythe- matosus in three ethnic groups:The effects of HLA classⅡ,C4,and CR1 alleles,socioeconomic factors,and ethnicity at disease onset. Arthritis Rheum,1998,41(7):1161-1172.
7. 王敏,董怡,赵怡,等.人类白细胞抗原 DR 基因与狼疮性肾炎的相关性探讨.中华肾脏病杂志,1997,3(6):323-326.
8. 彭学标综述.HLA-Ⅱ类基因与系统性红斑狼疮易感性.国外医学皮肤性病学分册,1996,12:18-21.
9. 施为,刘稚然,谢红付. 系统性红斑狼疮患者 HLA-DQ 基因与自身抗体及肾脏受累的研究.中华皮肤科杂志,2001,34(3):222-223.
10. 熊平,杨颖,龚非力.一种新的 HLA-Ⅱ类基因分型方法----PCR-SSP 技术的建立.免疫学杂志,1996,12940:258-261.
11. Marsh SGE,Bodmer JG.HLA class region nucleotide sequences. TissueAntigens,1995,46:258-280.
12. 龙桂芳,阿卜迪,李卫,等.应用序列特异引物 PCR 法对广西壮族 HLA-DQA1 进行基因分型.中华血液学杂志,1995,16(10):532-534.
13. 刘栋华,梁伶,苏家光,等.广西地区壮族系统性红斑狼疮与 HLA-DQA1 等位基因的相关性研究.中国皮肤性病学杂志,2004,8(18):449-450.
14. Skarsvag S,Hansen KE,Holst, et al.Distribution of HLA class Ⅱalleles among Scandinavian patients with systemic lupus erythe- matosus. Scand J Immunol,1995,42(5):564-571
15. Yao Z,Kimura a,Hartung K et al. Polomorphism of HLA-DQA1 promoter region(QAP)and DRB1,QAP,DQA1,DQB1 haplotypes in SLE,SLE Study Group Members.Immunogenetics,1993,38(6):421-429.
16. 潘星华,陆建荣,猪子英俊,等.中国汉人 HLA-DQAl 基因对系统性红斑狼疮的遗传易感性研究.中国免疫学杂志,1995,11(1):19-22.
17. 查旭山,禤国维,陈红,等.广东籍汉人 HLA-DQA DQB 基因与 SLE 的易感性研究.中国皮肤性病学杂志,2004,2(7):86-87.
18. Marchini M,Antonioli R,Lleo A,et al.HLA class Ⅱ antigens associated with lupus nephritis in Intalian SLE patients.Hum Immunol,2003,64(4):462-468.
19. Azizah MR,Aninoi SS,Kuak SH et al.The association of the HLA class II antigens with clinical and autoantibody expression in Malaysian Chinese patients with systemic lupus erythematosus. Asian Pac J auergy Immunol,2001,19(2):93-100.
20. 谢尚葵、冯树芳、沈福民,等.系统性红斑狼疮临床表现与 HLA-Ⅱ类单倍型关联的研究.中华微生物和免疫学杂志,2000,20(1):66-69.
21. MorimotoS, HashimotoH, YamanakaK, etal. Multicenter cooperative study of HLA class Ⅱ alleles in Japanese patients with SLE, Morden Rheumatology,2000,22(2):71-76.
1 Trowsdale J. Major histocopatibility complex .Res-Immunol,1997,148(6):425-426.
2 曹孟德,秦东春,孙含笑..HLA 分子生物学及临床应用,郑州:河南医科大学出版社.1998:147-150.
3 李霞,朱运良. HLA 与自身免疫性疾病研究进展. 国外医学免疫学分册,1999,22(2):75-78.
4 周光严.主要组织相容性复合体和特异性免疫应答.中华消化内科杂志,1995,15(2):100-102.
5 Galeazzi M, Annunziata P, Sebastiani GD, et al. Anti-GM1 in a large cohort of European patient with SLE and HLA class Ⅱ gene associations. J Rheumatol. 2002,27(1):135-141.
6 Lee AH, Bateman AC, Tumer SJ, et al. HLA class Ⅱ DRB1 and DQB1 allelic polymorphism and sclerosing lymphocytic lobulitis of the breast. J Clin Pathol, 1999,52(6):445-449.
7 Skarsvag S,Hansen KE,Holst, et al.Distribution of HLA class Ⅱalleles among Scandinavian patients with systemic lupus erythematosus. Scand J Immunol,1995,42(5):564-571.
8 Reveille JD,Schrohenloher RE,Acton RT, et al.DNA analysis of HLA-DR and DQ genes in Americans blacks with systemic lupus erythematosus .Arthritis Rheum,1989,32(10):1243-1251.
9 Yao Z,Kimura a,Hartung K et al. Polomorphism of HLA-DQA1 promoter region(QAP)and DRB1,QAP,DQA1,DQB1 haplotypes in SLE,SLE Study Group Members.Immunogenetics,1993,38(6): 421-429.
10 Dong RP,Kimura A,Hashimoto H,et al.Difference in HLA linked genetic backgroud between MCTD and SLE.Tissue Antigens,1993,41(1):20-25.
11 Doherty DG,Ireland R,Demaine AG,et al.MHC and susceptibility to SLE in southern Chinese.Arthritis Rheum,1992,35(6):641-646.
12 De Juan,Maritin JM,Gomez Reino JJ,et al. Differential contribution of C4 and HLA-DQ genes to systemic lupus erythematosus susceptibility. Hum Genet,1993 ,91(6):579-584.
13 张咸宁,潘星华,朱定良,等.中国南方汉族人群 HLA-DQB1 基因对系统性红斑狼疮的易感性研究.中国免疫学杂志,1997,13(1):37-39.
14 郑文军,梁伶,苏家光,等.广西地区汉族系统性红斑狼疮与 HLA-DRB1 等位基因的相关性研究.广西医科大学学报,2004,21(3):336-338.
15 刘栋华,梁伶,苏家光,等. 广西地区壮族系统性红斑狼疮与HLA-DQA1等位基因的相关性研究.中国皮肤性病学杂志,2004,8(18):449-450.
16 曹秀菁,叶冬青,李向培,等.皖籍汉人 HLA-DQA1 基因型与 SLE 相关性研究.中国皮肤性病学杂志,2004,18(2):83-85.
17 Marchini M,Antonioli R,Lleo A,et al.HLA class Ⅱ antigens associated with lupus nephritis in Intalian SLE patients.Hum Immunol,2003,64(4):462-468.
18 Azizah MR,Aninoi SS,Kuak SH et al. The association of the HLA class II antigens with clinical and autoantibody expression inMalaysian Chinese patients with systemic lupus erythematosus.Asian Pac J auergy Immunol;2001,19(2):93-100.
19 MorimotoS, HashimotoH, YamanakaK, et al. Multicenter cooperative study of HLA class Ⅱ alleles in Japanese patients with SLE, Morden Rheumatology,2000,22(2):71-76.
20 Kim TG, Kim HY, Lee SH, et al. systemic lupus erythematosus with nephritis is strongly associated with the TNFB*2 hemozygote in Korean population.Hum Immunol,1996,46(1):10-17.
21 王敏,董怡,赵怡,等.人类白细胞抗原 DR 基因与狼疮性肾炎的相关性探讨.中华肾脏病杂志,1997,3(6):323-326.
22 谢尚葵,冯树芳,沈福民,等.系统性红斑狼疮临床表现与 HLA-Ⅱ类单倍型关联的研究.中华微生物和免疫学杂志,2000,20(1):66-69.
23 David Lawrence. The single nucleotide polymorphism of PCDG-1 in European patients with SLE. Lancet, 2002,320:1399-1405.
24 冯学兵,沈南,陈顺乐等. 中国人群 16 号染色体 q12 区存在系统性红斑狼疮易感基因.中华医学遗传学杂志,2003,20(1):27-30.