Esposito L, Lampasona V, Bonifacio E, Bosi E, Ferrari M
Department of Laboratory Medicine of the Istituto Scientifico San Raffaele, Milan, Italy.
J Autoimmun. 1997 Aug;10(4):395-400. doi: 10.1006/jaut.1997.0144.
Considerable evidence exists that the genes coding for the HLA class II DQ molecules in the MHC region are major contributors to genetic susceptibility in insulin-dependent diabetes. Located centromeric to the DQ loci are the genes encoding DMA and DMB, two class II-like molecules which play an essential role in the pathway leading to antigen presentation by HLA class II. In this study we have examined the distribution of the DMB allele and studied HLA DQA1-DQB1-TAP2-DMB haplotypes in 52 IDDM families and 65 un-related controls. DMB allele frequencies in IDDM and control subjects were not significantly different. DMB0101 was present in 85% of patients vs. 76% of controls, DMB0102 in 12 vs. 17%, DMB0103 in 3 vs. 5%, DMB0104 in 0 vs. 2%. The IDDM-susceptible MHC DQA1-DQB1 haplotypes found by analysis of IDDM families were not associated with specific DMB alleles. We conclude that the described DMB polymorphisms are not associated with IDDM susceptibility and DMB genotyping is unlikely to improve the assessment of genetic risk for IDDM.
有大量证据表明,位于主要组织相容性复合体(MHC)区域的编码HLA - II类DQ分子的基因是胰岛素依赖型糖尿病遗传易感性的主要因素。在DQ基因座着丝粒方向的是编码DMA和DMB的基因,这两种II类样分子在HLA - II类分子提呈抗原的途径中起重要作用。在本研究中,我们检测了52个胰岛素依赖型糖尿病(IDDM)家系和65名无关对照中DMB等位基因的分布,并研究了HLA DQA1 - DQB1 - TAP2 - DMB单倍型。IDDM患者和对照人群中DMB等位基因频率无显著差异。DMB0101在85%的患者中出现,对照中为76%;DMB0102在患者中为12%,对照中为17%;DMB0103在患者中为3%,对照中为5%;DMB0104在患者中为0,对照中为2%。通过对IDDM家系分析发现的IDDM易感MHC DQA1 - DQB1单倍型与特定的DMB等位基因无关。我们得出结论,所描述的DMB多态性与IDDM易感性无关,DMB基因分型不太可能改善IDDM遗传风险的评估。