Rani R, Sood A, Lazaro A M, Stastny P
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8886, USA.
Hum Immunol. 1999 Jun;60(6):524-31. doi: 10.1016/s0198-8859(99)00032-4.
Thirty-four insulin-dependent diabetes mellitus (IDDM) patients from North India were studied with respect to their HLA class II alleles including those of the DRB1, DQA1, DQB1 and DPB1 loci, using the polymerase chain reaction (PCR) and hybridization with sequence-specific oligonucleotide probes (SSOP). They were compared with the class II alleles of 94 normal adult controls from the same ethnic background. The results show a statistically significant increase of DRB103011 (p < 0.00001), DQB10201 (p < 0.007), DQA10501 (0.0027) and DPB12601 (p < 0.0042) in patients compared to controls. DR04 was not significantly increased. However, homozygosity for DRB103011 was increased more than expected. DRB11501 and 1502 did not show a significant decrease in the patients. However, DRB10701 was decreased significantly, but this difference did not remain significant when the p value was corrected for the number of alleles tested. Similarly, DPB12601 was increased significantly in the patients but did not remain significant after p was corrected for the number of alleles tested. However, DPB12601 was increased, and remained significant after correction, in patients not having HLA-DR3. We also studied the possible role of aspartic acid at codon 57 of the DQ beta chain in protection against development of diabetes, and arginine at codon 52 of the DQ alpha chain in susceptibility. We observed an increase in non-Asp57 alleles in DQ beta and Arg52 in DQ alpha in the patients, however, this effect seems to be due to the fact that the most prevalent haplotype in diabetic patients: DRB103011-DQA10501-DQB10201, has DQB1 and DQA1 alleles which carry non-Asp57 and Arg52, respectively.
我们使用聚合酶链反应(PCR)以及与序列特异性寡核苷酸探针(SSOP)杂交的方法,对来自印度北部的34名胰岛素依赖型糖尿病(IDDM)患者的HLA II类等位基因进行了研究,这些等位基因包括DRB1、DQA1、DQB1和DPB1位点的等位基因。我们将他们与94名来自相同种族背景的正常成年对照者的II类等位基因进行了比较。结果显示,与对照组相比,患者中DRB103011(p < 0.00001)、DQB10201(p < 0.007)、DQA10501(0.0027)和DPB12601(p < 0.0042)的频率有统计学意义的显著增加。DR04没有显著增加。然而,DRB103011的纯合性增加超过预期。DRB11501和1502在患者中没有显示出显著下降。然而,DRB10701显著下降,但在根据检测的等位基因数量校正p值后,这种差异不再显著。同样,DPB12601在患者中显著增加,但在根据检测的等位基因数量校正p值后不再显著。然而,在没有HLA-DR3的患者中,DPB12601增加,并且在校正后仍然显著。我们还研究了DQβ链第57位密码子的天冬氨酸在预防糖尿病发生中的可能作用,以及DQα链第52位密码子的精氨酸在易感性中的作用。我们观察到患者中DQβ链非Asp57等位基因和DQα链Arg52增加,然而,这种效应似乎是由于糖尿病患者中最常见的单倍型:DRB103011-DQA10501-DQB10201,其DQB1和DQA1等位基因分别携带非Asp57和Arg52。