Maclaren N, Riley W, Skordis N, Atkinson M, Spillar R, Silverstein J, Klein R, Vadheim C, Rotter J
Department of Pathology, University of Florida College of Medicine, Gainesville 32610.
Autoimmunity. 1988;1(3):197-205. doi: 10.3109/08916938808997164.
Of the HLA allelic associations with insulin-dependent diabetes (IDD) reported to date. DR3 and DR4 have been the most positive and DR2 the most negative. In 952 Caucasian proband patients reported here, only 57 or 6% had no DR3 or DR4 alleles. When these 57 patients were compared to 249 Caucasian controls similarly lacking DR3 and DR4 antigens, there were excesses of DR1 (P = 0.13) and DRW8 (P = 0.01) and deficiencies of DR2 (P = 0.03) and DR5 (P = 0.03) in the patient group. The most common phenotype in this group of patients was DR1/DR7 (12.3%). Only four DR-homozygous patients involving alleles other than DR3 and DR4 were found by genotyping, and all were DR1 homozygotes. Among 506 patients wuth DR3/DRX or DR4/DRX phenotypes, DR1 was more frequent (P = 0.001; Bonferronni P = 0.006), and DR2 (P = 0.001) and DR5 (P = 0.001) less frequent than 243 HLA-matched controls. Of 187 patients with a single DR3 and no DR4, DR1 was more frequent (P = 0.02), with DR2 (P = 0.001) and DR5 (P = 0.02) less frequent than 94 HLA DR-compatible controls. Among 319 patients with a single DR4 but no DR3, DR1 was again more frequent (P = 0.01) and DR2 (P = 0.001) and DR5 (P = 0.001) less frequent than 149 HLA-matched controls. We conclude that DR1 is an additional risk DR allele for IDD to that of DR3 and DR4, and DR5 an additional protective DR allele to that of DR2.
在迄今报道的与胰岛素依赖型糖尿病（IDD）相关的HLA等位基因中，DR3和DR4呈最显著正相关，DR2呈最显著负相关。在本文报道的952名白种人先证者患者中，只有57名（6%）没有DR3或DR4等位基因。当将这57名患者与同样缺乏DR3和DR4抗原的249名白种人对照进行比较时，患者组中DR1（P = 0.13）和DRW8（P = 0.01）增多，DR2（P = 0.03）和DR5（P = 0.03）减少。该组患者中最常见的表型是DR1/DR7（12.3%）。通过基因分型仅发现4名涉及DR3和DR4以外等位基因的DR纯合子患者，且均为DR1纯合子。在506名具有DR3/DRX或DR4/DRX表型的患者中，DR1比243名HLA匹配对照更常见（P = 0.001；Bonferronni P = 0.006），而DR2（P = 0.001）和DR5（P = 0.001）则较少见。在187名仅有一个DR3且无DR4的患者中，DR1比94名HLA DR相容对照更常见（P = 0.02），DR2（P = 0.001）和DR5（P = 0.02）则较少见。在319名仅有一个DR4但无DR3的患者中，DR1同样比149名HLA匹配对照更常见（P = 0.01），DR2（P = 0.001）和DR5（P = 0.001）则较少见。我们得出结论，对于IDD而言，DR1是除DR3和DR4之外的另一个风险DR等位基因，而DR5是除DR2之外的另一个保护性DR等位基因。
