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中国汉族人群中 HLA Ⅰ类和Ⅱ类等位基因与大疱性类天疱疮的关联。

Association of HLA class I and class II alleles with bullous pemphigoid in Chinese Hans.

机构信息

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, China.

Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.

出版信息

J Dermatol Sci. 2018 Mar;89(3):258-262. doi: 10.1016/j.jdermsci.2017.11.014. Epub 2017 Dec 2.

Abstract

BACKGROUND

Bullous pemphigoid (BP) is one of the most common autoimmune skin diseases. Associations of genes, especially human leukocyte antigen (HLA)-DQ alleles, with BP indicate that genetic predisposition contributes to the disease.

OBJECTIVES

To evaluate the association of HLA class I and HLA class II alleles with susceptibility to BP in the northern Chinese Han population.

METHODS

We performed genotype for HLA-A, -B, -C, -G, -DPA1, -DPB1, -DQA1, -DQB1 and -DRB1 loci in 105 patients with BP by Sanger sequence-based typing (SBT) method. These data were compared with a local control cohort of 420 age- and sex-matched cases.

RESULTS

Among the HLA alleles described herein, the susceptibility alleles associated with a high prevalence of BP were A11:01 (OR = 1.9 Pc = 0.017); B37:01 (OR = 8, Pc = 1.811 × 10); G01:01 (OR = 3.61, Pc = 2.839 × 10) and G01:06 (OR = 2.22, Pc = 0.025); DQA101:05 (OR = 4.87, Pc = 5.822 × 10), DQA105:05 (OR = 2.64, Pc = 9.114 × 10), and DQA105:08 (OR = 10.2, Pc = 0.016); DQB103:01 (OR = 1.69, Pc = 0.048) and DQB105:01 (OR = 3.42, Pc = 7.28 × 10); and DRB110:01 (OR = 6.85, Pc = 2.63 × 10). To the contrary, HLA-DQA101:02 (OR = 0.46, Pc = 8.603 × 10) and DQA101:03 (OR = 0.38, Pc = 0.048); DQB102:02 (OR = 0.28, Pc = 0.016); and DRB107:01 (OR = 0.26, Pc = 0.004) had significant associations with protection against BP. In addition, the frequency of haplotype HLA-DRB113-DQA105-DQB1*03 (OR = 12.32, Pc = 0.026) in BP patients was significantly higher than those in controls.

CONCLUSION

Our data demonstrated that the alleles and haplotypes found in this study may be important differential genetic markers for susceptibility to or protection against BP in individuals of northern Chinese Han population.

摘要

背景

大疱性类天疱疮(BP)是最常见的自身免疫性皮肤病之一。基因,尤其是人类白细胞抗原(HLA)-DQ 等位基因与 BP 的关联表明遗传易感性是疾病的一个重要因素。

目的

评估 HLA Ⅰ类和 HLA Ⅱ类等位基因与中国北方汉族人群 BP 易感性的关系。

方法

我们采用 Sanger 测序(SBT)方法对 105 例 BP 患者和 420 名年龄和性别匹配的本地对照者的 HLA-A、-B、-C、-G、-DPA1、-DPB1、-DQA1、-DQB1 和-DRB1 基因座进行基因分型。

结果

在所描述的 HLA 等位基因中,与 BP 高患病率相关的易感等位基因包括 A11:01(OR=1.9,Pc=0.017);B37:01(OR=8,Pc=1.811×10);G01:01(OR=3.61,Pc=2.839×10)和 G01:06(OR=2.22,Pc=0.025);DQA101:05(OR=4.87,Pc=5.822×10),DQA105:05(OR=2.64,Pc=9.114×10)和 DQA105:08(OR=10.2,Pc=0.016);DQB103:01(OR=1.69,Pc=0.048)和 DQB105:01(OR=3.42,Pc=7.28×10);和 DRB110:01(OR=6.85,Pc=2.63×10)。相反,HLA-DQA101:02(OR=0.46,Pc=8.603×10)和 DQA101:03(OR=0.38,Pc=0.048);DQB102:02(OR=0.28,Pc=0.016);和 DRB107:01(OR=0.26,Pc=0.004)与 BP 具有显著的保护作用。此外,BP 患者 HLA-DRB113-DQA105-DQB1*03 单体型的频率(OR=12.32,Pc=0.026)明显高于对照组。

结论

本研究发现的等位基因和单体型可能是中国北方汉族人群 BP 易感性或保护性的重要遗传标志。

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