中国南方汉族重型斑秃与HLA-DRB1等位基因的相关性研究
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摘要
研究背景
斑秃(alopecia areata)是一种常见的毛发疾病,呈局限性斑片状脱发,常表现为多灶性。本病在一般人群的患病率约为0.1-0.2%,约占皮肤科门诊初诊患者的2%,其中5%-7%患者病情严重,可发展为全秃(alopecia totalis, AT)和普秃(alopecia universalis, AU)。斑秃尤其是重型斑秃不仅仅是美容问题,还会给患者带来很大的精神负担,激发感情脆弱,丧失自信等心理问题,常严重影响患者的工作和生活。目前,斑秃尤其是重型斑秃治疗比较困难,而且病情容易反复,迁延,是近年来毛发疾病研究的热点和难点。
斑秃的病因尚不明确。目前普遍认为斑秃是一种T淋巴细胞介导的针对毛囊的自身免疫性疾病,是在遗传素质和环境诱发因素相互作用下产生的一种多基因疾病。近来的研究表明斑秃和HLA-Ⅱ类等位基因有很强的关联性,而HLA-Ⅱ类分子中以DRB1最具多态性,对于免疫应答起决定性作用,且迄今所建立的HLA分型技术对HLA-DRB1多态性的分析最为成熟。国内外通过对斑秃的研究发现,某些HLA-DRB1等位基因与斑秃的轻重程度有相关性,而且在不同的种族和地区人群中存在着差异。目前关于中国南方汉族重型斑秃与HLA-DRB1等位基因相关性的报道较少。
研究目的
探讨中国南方汉族人群重型斑秃与HLA-DRB1等位基因的相关性。
研究方法
采用直接测序分型-聚合酶链反应(PCR-SBT)技术对已确诊的72例中国南方地区汉族重型斑秃和40例轻型斑秃患者进行HLA-DRB1基因多态性分析。正常对照采用已知的中国南方汉族5645例健康患者HLA-DRB1等位基因频率。采用χ2检验比较各等位基因频率的差异。
研究结果
轻型斑秃组HLA-DRB1*03等位基因频率较正常对照组显著升高(χ2 =15.729,P=0.000,OR=11.802),而重型斑秃组与正常对照组比差异无显著性意义。
重型斑秃组HLA-DRB1*04等位基因频率较正常对照组显著升高(χ2=24.358,P=0.000,OR=3.057),轻型斑秃组与正常对照组比差异无显著意义。
HLA-DRB1*07等位基因频率在重型斑秃组明显降低(χ2 =5.033,P=0.025,OR=0.143),而轻型斑秃组与正常对照组比差异无显著性意义。
HLA-DRB1*09等位基因频率在重型斑秃组也明显降低(χ2 =4.114,P=0.043,OR=0.558),轻型斑秃组与正常对照组比差异无显著性意义。
重型、轻型斑秃的HLA-DRB1*01、05、08、11、12、13、14、15、16等位基因频率与正常对照组比差异无统计学意义。
结论
HLA-DRB1*03、04、07、09等位基因与中国南方汉族斑秃病情严重程度相关。重型斑秃中HLA-DRB1*07、09等位基因频率明显降低,可能是重型斑秃的保护基因;而HLA-DRB1*04等位基因的频率升高,可能是重型斑秃的易感基因。轻型斑秃组HLA-DRB1*03等位基因频率升高。
Background
Alopecia aerata (AA) is an disease that presents as well defined patches of nonscarring hair loss with no overt epidermal changes. The lifetime prevalence of alopecia areata is estimated to be 0.1-0.2% of population in USA. It represents about 2% of the total dermatology outpatients in China. It is estimated that 5-7% of alopecia areata patients are severe cases. These patients can develop into alopecia totalis (AT) and alopecia universalis (AU). Severe alopecia areata is not only affect patient’s apperance, but also leading to psychological problems. Currently, it is difficult for treatments. Thus, severe alopecia areata is still a therapeutic challenge for dermotologists.
The etiopathogenesis of AA is not completely understood. Alopecia areata (AA) is a follicular T cell-mediated, multigene, multifactorial and autoimmune disease. The susceptibility of AA depends on the interaction of multiple genes. Previous studies have shown that HLA-Ⅱi s closely related to AA. Among HLA-Ⅱs ubtype, DRB1 is the highest genetic polymorphism and play critical roles in immune response. Furthermore, analysis of genetic polymorphism of HLA-DRB1 has been well developed. Previous studies have shown that HLA-DRB1 is related to the severity of AA, and expressions of HLA-DRB1 are different among peoples in different races and regions. Currently, there are only limited data on association of severe AA and HLA-DRB1 alleles in Southern Chinese Han.
Objective
This study was to investigate the association between severe alopecia areata and HLA-DRB1 alleles in Southern Chinese Han.
Methods
A total of 72 patients with severe alopecia areata and 40 patients with mild alopecia areata were recruited from the same ethnic group (Han nationality) and different parts of Southern Chinese and related laboratory tests HLA typing (HLA-DRB1) was performed by polymerase chain reaction (PCR) using sequence based typing (SBT). Their HLA typing results were compared with control population of the same ethnic group and the same area (published data). The frequency of DRB1 alleles from patients and controls were compared using chi square analysis of 2 x 2 tables and strength of associations was estimated by odd ratio (OR).
Results
There was significant statistical between mild AA group and control group in the frequency of HLA-DRB1*03, whereas, the frequency of HLA-DRB1*03 in severe AA group show no significantly difference as compared with control group.
The frequency of HLA-DRB1*04 in mild AA group was no difference, whereas, there was significantly statistical difference betwwen severe AA group and control group in the frequency of HLA-DRB1*04.
The frequency of HLA-DRB1*07 decreased in severe AA, appearing a statistical difference between severe AA and control (χ2=5.033, P=0.025, OR=0.143), wheras between mild AA and control, there was no difference.
The frequency of HLA-DRB1*09 decreased in severe AA, showing a considerable difference between severe AA and control group (χ2=4.114, P=0.043, OR=0.558), between mild AA and control, there was no difference.
No significant association was found between HLA-DRB1*01, 05, 08, 11, 12, 13, 14, 15, 16.
Conclusion
There was a relationship between severity of disease and HLA-DRB1*03, 04, 07, 09 in Southern Chiense Han alopecia areata. The frequency of HLA-DRB1*07, 09 were decreased in severe AA. Wheras, the frequency of HLA-DRB1*04 were increased in severe AA. These results suggested that HLA-DRB1*04 may be high risk genes for severe AA. HLA-DRB1*07, 09 may be protective genes for severe AA. The frequency of HLA-DRB1*03 was increased in mild alopecia areata.
斑秃(alopecia areata)是一种常见的毛发疾病,呈局限性斑片状脱发,常表现为多灶性。本病在一般人群的患病率约为0.1-0.2%,约占皮肤科门诊初诊患者的2%,其中5%-7%患者病情严重,可发展为全秃(alopecia totalis, AT)和普秃(alopecia universalis, AU)。斑秃尤其是重型斑秃不仅仅是美容问题,还会给患者带来很大的精神负担,激发感情脆弱,丧失自信等心理问题,常严重影响患者的工作和生活。目前,斑秃尤其是重型斑秃治疗比较困难,而且病情容易反复,迁延,是近年来毛发疾病研究的热点和难点。
斑秃的病因尚不明确。目前普遍认为斑秃是一种T淋巴细胞介导的针对毛囊的自身免疫性疾病,是在遗传素质和环境诱发因素相互作用下产生的一种多基因疾病。近来的研究表明斑秃和HLA-Ⅱ类等位基因有很强的关联性,而HLA-Ⅱ类分子中以DRB1最具多态性,对于免疫应答起决定性作用,且迄今所建立的HLA分型技术对HLA-DRB1多态性的分析最为成熟。国内外通过对斑秃的研究发现,某些HLA-DRB1等位基因与斑秃的轻重程度有相关性,而且在不同的种族和地区人群中存在着差异。目前关于中国南方汉族重型斑秃与HLA-DRB1等位基因相关性的报道较少。
研究目的
探讨中国南方汉族人群重型斑秃与HLA-DRB1等位基因的相关性。
研究方法
采用直接测序分型-聚合酶链反应(PCR-SBT)技术对已确诊的72例中国南方地区汉族重型斑秃和40例轻型斑秃患者进行HLA-DRB1基因多态性分析。正常对照采用已知的中国南方汉族5645例健康患者HLA-DRB1等位基因频率。采用χ2检验比较各等位基因频率的差异。
研究结果
轻型斑秃组HLA-DRB1*03等位基因频率较正常对照组显著升高(χ2 =15.729,P=0.000,OR=11.802),而重型斑秃组与正常对照组比差异无显著性意义。
重型斑秃组HLA-DRB1*04等位基因频率较正常对照组显著升高(χ2=24.358,P=0.000,OR=3.057),轻型斑秃组与正常对照组比差异无显著意义。
HLA-DRB1*07等位基因频率在重型斑秃组明显降低(χ2 =5.033,P=0.025,OR=0.143),而轻型斑秃组与正常对照组比差异无显著性意义。
HLA-DRB1*09等位基因频率在重型斑秃组也明显降低(χ2 =4.114,P=0.043,OR=0.558),轻型斑秃组与正常对照组比差异无显著性意义。
重型、轻型斑秃的HLA-DRB1*01、05、08、11、12、13、14、15、16等位基因频率与正常对照组比差异无统计学意义。
结论
HLA-DRB1*03、04、07、09等位基因与中国南方汉族斑秃病情严重程度相关。重型斑秃中HLA-DRB1*07、09等位基因频率明显降低,可能是重型斑秃的保护基因;而HLA-DRB1*04等位基因的频率升高,可能是重型斑秃的易感基因。轻型斑秃组HLA-DRB1*03等位基因频率升高。
Background
Alopecia aerata (AA) is an disease that presents as well defined patches of nonscarring hair loss with no overt epidermal changes. The lifetime prevalence of alopecia areata is estimated to be 0.1-0.2% of population in USA. It represents about 2% of the total dermatology outpatients in China. It is estimated that 5-7% of alopecia areata patients are severe cases. These patients can develop into alopecia totalis (AT) and alopecia universalis (AU). Severe alopecia areata is not only affect patient’s apperance, but also leading to psychological problems. Currently, it is difficult for treatments. Thus, severe alopecia areata is still a therapeutic challenge for dermotologists.
The etiopathogenesis of AA is not completely understood. Alopecia areata (AA) is a follicular T cell-mediated, multigene, multifactorial and autoimmune disease. The susceptibility of AA depends on the interaction of multiple genes. Previous studies have shown that HLA-Ⅱi s closely related to AA. Among HLA-Ⅱs ubtype, DRB1 is the highest genetic polymorphism and play critical roles in immune response. Furthermore, analysis of genetic polymorphism of HLA-DRB1 has been well developed. Previous studies have shown that HLA-DRB1 is related to the severity of AA, and expressions of HLA-DRB1 are different among peoples in different races and regions. Currently, there are only limited data on association of severe AA and HLA-DRB1 alleles in Southern Chinese Han.
Objective
This study was to investigate the association between severe alopecia areata and HLA-DRB1 alleles in Southern Chinese Han.
Methods
A total of 72 patients with severe alopecia areata and 40 patients with mild alopecia areata were recruited from the same ethnic group (Han nationality) and different parts of Southern Chinese and related laboratory tests HLA typing (HLA-DRB1) was performed by polymerase chain reaction (PCR) using sequence based typing (SBT). Their HLA typing results were compared with control population of the same ethnic group and the same area (published data). The frequency of DRB1 alleles from patients and controls were compared using chi square analysis of 2 x 2 tables and strength of associations was estimated by odd ratio (OR).
Results
There was significant statistical between mild AA group and control group in the frequency of HLA-DRB1*03, whereas, the frequency of HLA-DRB1*03 in severe AA group show no significantly difference as compared with control group.
The frequency of HLA-DRB1*04 in mild AA group was no difference, whereas, there was significantly statistical difference betwwen severe AA group and control group in the frequency of HLA-DRB1*04.
The frequency of HLA-DRB1*07 decreased in severe AA, appearing a statistical difference between severe AA and control (χ2=5.033, P=0.025, OR=0.143), wheras between mild AA and control, there was no difference.
The frequency of HLA-DRB1*09 decreased in severe AA, showing a considerable difference between severe AA and control group (χ2=4.114, P=0.043, OR=0.558), between mild AA and control, there was no difference.
No significant association was found between HLA-DRB1*01, 05, 08, 11, 12, 13, 14, 15, 16.
Conclusion
There was a relationship between severity of disease and HLA-DRB1*03, 04, 07, 09 in Southern Chiense Han alopecia areata. The frequency of HLA-DRB1*07, 09 were decreased in severe AA. Wheras, the frequency of HLA-DRB1*04 were increased in severe AA. These results suggested that HLA-DRB1*04 may be high risk genes for severe AA. HLA-DRB1*07, 09 may be protective genes for severe AA. The frequency of HLA-DRB1*03 was increased in mild alopecia areata.
引文
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