等位基因與中國人第一型糖尿病的關係

等位基因與中國人第一型糖尿病的關係

Relationship Between HLA-DMA, DMB Alleles and Type 1 Diabetes in Chinese
HLA-DMA、DMB

YM Sang, C Yan, C Zhu, GC Ni, YM Hu

Department of Endocrinology, Beijing Children's Hospital affiliated to Capital University of Medicine Science Fuxingmenwai, Nanlishi Road 56, Beijing 100045, China

YM Sang ( 桑艷梅 ) MD
C Yan ( 顏純 ) BSc
C Zhu ( 朱逞 ) BSc
GC Ni ( 倪桂臣 ) BSc
YM Hu ( 胡亞美 ) BSc

Correspondence to: Dr YM Sang

Received March 24, 2004

Abstract

The Human Leucocyte Antigen (HLA)-DMA and DMB genes are located in the HLA-D region between DQ and DP. HLA-DM molecules play an important role in the process of peptide loading to HLA class II antigens, both in regulating the dissociation of class II-associated invariant chain peptides (CLIP) and the subsequent binding of exogenous peptides to HLA class II molecules. In order to investigate the immunogenetic heterogeneity within the HLA-D region, we designed this study to explore the relationship between HLA-DMA, DMB, and genetic susceptibility to type 1 diabetes in Chinese. Our results showed that HLA-DMA*0103 and HLA-DMB*0103 alleles contributed to the predisposition, while HLA-DMA*0102 and HLA-DMB*0101 alleles conferred protection to type 1 diabetes in Chinese. HLA-DMA*0101/0102 and DMB*0101/0101 genotypes were significantly increased in the controls, HLA-DMB*0103/0103 and DMA*0101/0103 genotypes were significantly increased in the patients. In Chinese, HLA-DMA*0102/DMB*0101 heterodimer confers protection to type 1 diabetes, while HLA-DMA*0103/DMB*0102, DMA*0103/DMB*0103 and DMA*0103/DMB*0101 heterodimers confer susceptibility to type 1 diabetes. In general, our study suggests that HLA-DMA and DMB genes may be associated with the susceptibility to type 1 diabetes in Chinese.

人類白細胞抗原（HLA）-DMA 和 DMB 基因位於 HLA-D 區 DQ 和 DP 之間。HLA-DM 分子在多定位於 HLAII 型抗原的過程中起重要作用，既調節 II 型抗原相關差異性鏈（CLIP）的分離，又調節隨後的外源性多與 HLAII 型分子的結合。我們研究了 HLA-DMA、DMB 和中國人一型糖尿病的基因易感性的關係，以便考察 HLA-D 區內的免疫遺傳學異源性。結果顯示 HLA-DMA*0103 和 HLA-DMB*0103 等位基因與中國人第一型糖尿病易感有關，而 HLA-DMA*0102 和 HLA-DMB*0101 等位基因則有保護作用。HLA-DMA*0101/0102 和 HLA-DMB*0101/0101 基因型在對照組中顯著性升高。HLA-DMB*0103/0103 和 HLA-DMA*0101/0103 基因型在病人組中顯著升高。在中國人中，HLA-DMA*0102/DMB*0101 異源二聚體對一型糖尿病有保護作用，而 HLA-DMA*0103/DMB*0102、 HLA-DMA*0103/DMB*0103 和 HLA-DMA*0103/DMB*0101 異源二聚體與 I 型糖尿病易感性有關。總而言之，我們的研究提示 HLA-DMA 和 DMB 基因可能與中國人第一型糖尿病易感性有關。

Keyword : Human leucocyte antigen; Non-classical gene; Type 1 diabetes

關鍵詞：人類白細胞抗原、非經典基因、I 型糖尿病、第一型糖尿病

HK J Paediatr (New Series)
Vol 10. No. 1, 2005

Lipoxen plc, of London, has entered into a materials transfer agreement for SuliXen with the Barbara Davis Center for Childhood Diabetes. Under the terms of the agreement, Lipoxen will provide the center with SuliXen for initial preclinical studies in models of diabetes. The evaluation is designed to explore whether SuliXen has the potential to reverse, limit or prevent the development of Type I diabetes. A similar evaluation will be conducted with Lantus (Sanofi-Aventis).