1型糖尿病患者自身抗体与HLA-A等位基因的关系
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国家自然科学基金资助项目(30671010)


Relationship between islet autoantibodies and HLA-A gene in type 1 diabetes mellitus
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    摘要:

    目的:探讨急性起病的1型糖尿病(T1DM)患者血清谷氨酸脱羧酶抗体(GADA)-胰岛细胞抗体(ICA)-胰岛素自身抗体(IAA)与HLA-A等位基因之间的关系-方法:采用酶联免疫吸附法(ELISA)定性检测104例江苏地区汉族T1DM患者与110例正常对照的GADA-ICA和IAA-从外周血中提取细胞基因组DNA,运用聚合酶链反应-寡核苷酸探针序列特异性引物(PCR-SSO)技术,检测T1DM患者和正常对照的HLA-A基因频率-应用SPSS11.0软件进行T1DM发病年龄及自身抗体与HLA-A基因频率的相关性分析-结果:T1DM组与正常对照组相比,A*03-A*24频率明显升高,A*01-A*11-A*31频率明显下降-起病年龄20岁以下的急性起病T1DM患者与20岁以上患者比较,携带HLA-A*24基因型频率增高,而 HLA-A*31等位基因频率减少-携带HLA-A*03等位基因的急性起病T1DM患者GADA-ICA阳性率高于不携带A*03者;携带HLA-A*24等位基因的急性起病T1DM者ICA阳性率高于不携带A*24者-结论:本研究发现在江苏地区急性起病的T1DM患者中,A*03-A*24是易感基因,而A*01-A*11-A*31是保护性基因,A*31可能延缓1型糖尿病的发病;A*31与发病年龄正相关,ICA-A*24与发病年龄负相关;A*03-A*24与GADA正相关,A*24与ICA正相关-

    Abstract:

    Objective:To explore the relationship between islet autoantibodies of glutamic acid decarboxylase antibody (GADA), islet cell antibody(ICA) and insulin autoantibody(IAA) and HLA-A gene in patients with type 1 diabetes mellitus(T1DM) in Jiangsu province. Methods: One hundred and four patients with type 1 diabetes in Chinese Han of Jiangsu area and 110 healthy controls were recruited and measured for GADA, IAA, ICA by ELISA. HLA-A typing was performed by polymerase chain reaction-sequence specific oligonucleotide primer(PCR-SSO) technology after extracted genomic DNA from peripheral blood cells. The HLA-A alleles frequencies were studied by Arlequin software. Then an analysis was made on the correlation between islet autoantibodies of GADA, IAA, ICA and HLA-A alleles in type 1 diabetes mellitus by SPSS 11.0. Results: The positivity frequencies of GADA, ICA and IAA in 104 type 1 diabetes patients were 64.4%, 39.4% and 37.5%, respectively. The frenquencies of HLA-A*03 and HLA-A*24 alleles in the patients were significantly higher than that in healthy control group. The frenquencies of HLA-A*01, HLA-A*11, HLA-A*31 alleles in the patients of acute autoimmune diabetes were significantly lower than those in the healthy control group. In patients, whose onset age <20 years, the frequency of A*24 alleles was higher than that in the patients with onset age ≥20 years, but the frequency of A*31 alleles in acute-onset autoimmune diabetes with onset age <20 years was lower than that in the patients with onset age ≥20 years. The frequencies of GADA, ICA positivity were higher in those patients with A*03 alleles than those in patients lacking it; the frequency of ICA positivity was higher in those patients with A*24 alleles than those in patients lacking it. Conclusion: Our findings show that HLA-A*03 and A*24 are susceptibility to acute-onset autoimmune diabetes, whereas HLA-A*01, A*11 and A*31 are protective in Jiangsu province. A*31 may delay the onset of acute-onset autoimmune diabetes, A*31 is correlated positively with age at onset; while ICA, A*24 are negatively correlated with age at onset. A*3, A*24 are positively correlated with GADA, and A*24 is positively correlated with ICA.

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罗 娜,朱 妍,张真稳,王 艳,王知笑,杨 涛.1型糖尿病患者自身抗体与HLA-A等位基因的关系[J].南京医科大学学报(自然科学版),2010,(11):1580-1583

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  • 收稿日期:2010-04-15
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