Henson V, Maclaren N, Riley W, Wakeland E K
Immunogenetics. 1987;25(3):152-60. doi: 10.1007/BF00344028.
The restriction fragment length polymorphism (RFLP) of DQ beta was assessed in a panel of control and insulin-dependent diabetes (IDD) patients who were serologically typed as HLA-DR4 homozygotes or HLA-DR3, DR4 heterozygotes. Digestions of genomic DNA with Bam HI, Bgl II, Pst I, Xba I, and Hind III revealed a total of 15 RFLPs in the panel of 71 HLA-DR4 chromosomes. These RFLPs were organized into six allelic groups on the basis of segregation analysis in families. Complete RFLP haplotypes for the 5 restriction enzymes could be constructed for 42 of the HLA-DR4 chromosomes. This analysis revealed 18 RFLP haplotypes of DQ beta associated with the DR4 chromosomes tested. Two of these haplotypes, designated DQ3.DR4. a and DQ3.DR4.b, accounted for over 50% of the DR4 chromosomes analyzed. These two haplotypes were antithetical for the RFLPs detected by all five enzymes, indicating that they represent very distinct forms of DQ beta. The remaining 16 haplotypes were infrequent or unique and were closely related to either a DQ3.DR4.a or DQ3.DR4.b. Two of the RFLPs detected, a 5.8 kb Bgl II fragment and a 10.5 kb Bam HI fragment, had increased frequencies in disease-associated chromosomes. However, none of the RFLPs we detected exhibited a statistically significant increase in IDD or control populations. In contrast, the DQ3.DR4.b DQ beta haplotype was significantly decreased in IDD-associated DR4 chromosomes (P = 0.04). These results suggest that the DQ3.DR4.b DQ beta allele may be protective for the development of IDD.
在一组对照者和胰岛素依赖型糖尿病（IDD）患者中评估了DQβ的限制性片段长度多态性（RFLP），这些患者血清学分型为HLA - DR4纯合子或HLA - DR3、DR4杂合子。用Bam HI、Bgl II、Pst I、Xba I和Hind III对基因组DNA进行酶切，在71条HLA - DR4染色体组成的样本中总共发现了15种RFLP。根据家系中的分离分析，这些RFLP被分为6个等位基因组。对于42条HLA - DR4染色体，可以构建出这5种限制性酶的完整RFLP单倍型。该分析揭示了与所检测的DR4染色体相关的18种DQβ的RFLP单倍型。其中两种单倍型，命名为DQ3.DR4.a和DQ3.DR4.b，占所分析的DR4染色体的50%以上。这两种单倍型在所有5种酶检测到的RFLP方面是相反的，表明它们代表了非常不同的DQβ形式。其余16种单倍型很少见或很独特，并且与DQ3.DR4.a或DQ3.DR4.b密切相关。所检测到的两种RFLP，一个5.8 kb的Bgl II片段和一个10.5 kb的Bam HI片段，在疾病相关染色体中的频率增加。然而，我们检测到的RFLP在IDD患者群体或对照群体中均未表现出统计学上的显著增加。相反，在与IDD相关的DR4染色体中，DQ3.DR4.b DQβ单倍型显著减少（P = 0.04）。这些结果表明，DQ3.DR4.b DQβ等位基因可能对IDD的发生具有保护作用。
