多腺体功能衰竭的早发与HLA - DRB1*03相关。

Early onset of polyglandular failure is associated with HLA-DRB1*03.

作者信息

Dittmar Manuela, Ide Maximilian, Wurm Michael, Kahaly George J

机构信息

Department of Medicine I, Gutenberg University Hospital, Mainz 55101, Germany.

出版信息

Eur J Endocrinol. 2008 Jul;159(1):55-60. doi: 10.1530/EJE-08-0082. Epub 2008 Apr 7.

DOI:10.1530/EJE-08-0082

PMID:18390988

Abstract

OBJECTIVES

Polyglandular failure or autoimmunity (PGA) involves at least two endocrine diseases. Several genes may play a role in its etiology. This study analyzed 1) whether HLA-DRB1, HLA-DQB1, and MHC class I chain-related gene A (MICA) polymorphisms are associated in PGA and 2) whether PGA patients display stronger associations with these immune genes than patients with monoglandular autoimmunity (MGA).

DESIGN

Association study.

METHODS

HLA-DRB1, HLA-DQB1, and MICA alleles were analyzed in 73 patients with PGA, 283 with MGA, and 206 healthy controls. The HLA-DRB1 and HLA-DQB1 polymorphisms were determined with PCR-amplified DNA being hybridized with PCR-sequence-specific oligonucleotide probes. MICA microsatellites were typed by PCR amplification and fragment size analysis on a DNA sequencer.

RESULTS

HLA-DRB103 was strongly increased in patients with PGA (50.7%) versus both controls (21.8%, P(c)<0.0001; RR=2.32, 95% CI=1.62-3.33) and MGA (11.4%, P(c)<0.0001). HLA-DRB103 was highly prevalent in PGA patients with early versus late disease onset (P<0.05, logistic regression analysis). HLA-DRB104 allele carriers were more present in PGA versus controls (53.4% vs 22.4%, P(c)<0.0001, RR=2.38, 95% CI=1.68-3.38). Further, HLA-DQB102 was increased in PGA versus controls (P(c)<0.01), whereas HLA-DQB106 was decreased (P(c)<0.001). Patients with PGA showed more MIC A5.1 and less MIC A6 allele carriers than controls (NS). Presence of the MIC A5.1 allele was not associated with the HLA-DRB103 or HLA-DQB1 alleles.

CONCLUSIONS

HLA-DRB1*03 is a stronger genetic marker in PGA than in MGA, foremost in those with early disease onset.

摘要

目的

多腺体功能衰竭或自身免疫（PGA）涉及至少两种内分泌疾病。多种基因可能在其病因中起作用。本研究分析了1）HLA - DRB1、HLA - DQB1和MHC I类链相关基因A（MICA）多态性是否与PGA相关，以及2）与单腺体自身免疫（MGA）患者相比，PGA患者是否与这些免疫基因有更强的关联。

设计

关联研究。

方法

对73例PGA患者、283例MGA患者和206例健康对照者进行HLA - DRB1、HLA - DQB1和MICA等位基因分析。采用PCR扩增DNA与PCR序列特异性寡核苷酸探针杂交的方法测定HLA - DRB1和HLA - DQB1多态性。通过PCR扩增和在DNA测序仪上进行片段大小分析对MICA微卫星进行分型。

结果

与对照组（21.8%，P(c)<0.0001；RR = 2.32，95% CI = 1.62 - 3.33）和MGA组（11.4%，P(c)<0.0001）相比，PGA患者中HLA - DRB103显著增加。HLA - DRB103在疾病早期发病的PGA患者中高度流行（P<0.05，逻辑回归分析）。与对照组相比，PGA患者中HLA - DRB104等位基因携带者更多（53.4%对22.4%，P(c)<0.0001，RR = 2.38，95% CI = 1.68 - 3.38）。此外，与对照组相比，PGA患者中HLA - DQB102增加（P(c)<0.01），而HLA - DQB106减少（P(c)<0.001）。与对照组相比，PGA患者中携带MICA 5.1的更多，携带MICA 6等位基因的更少（无统计学意义）。MICA 5.1等位基因的存在与HLA - DRB103或HLA - DQB1等位基因无关。