成人自身免疫性多腺体综合征的发生与HLA II类基因多态性之间的关联，以及在这些综合征背景下慢性肾上腺功能不全发生的易感性。

The association between the development of autoimmune polyglandular syndrome in adults and polymorphism of HLA class II genes and the predisposition to the development of chronic adrenal insufficiency in the context of these syndromes.

作者信息

Larina A A, Troshina E A, Ivanova O N

机构信息

National Medical Research Center of Endocrinology, Ministry of Health of Russia, Moscow, Russia.

出版信息

Ter Arkh. 2018 Nov 22;90(10):23-29. doi: 10.26442/terarkh2018901023-29.

DOI:10.26442/terarkh2018901023-29

PMID:30701791

Abstract

AIM

To consider association of chronic adrenal insufficiency in patients with APS of adults with polymorphism of class II HLA genes, -CTLA-4 and PTPN-22.

MATERIALS AND METHODS

The case-control study involved 78 patients with APS 2, 3, 4 types and 109 healthy subjects). Alleles of the HLA class II genes, CTLA-4 and PTPN-22 were identified by the multiprimer allele-specific PCR method. The statistical analysis was carried out using the exact two-sided Fisher test. The association of the chronic adrenal insufficiency in patients with APS was determined by the value of the odds ratio (OR - odd's ratio), the value of 95% confidence interval (95% CI - confidence interval).

RESULTS

Haplotypes DR3-DQ2 (OR = 4.06), DR4-DQ8 (OR = 5.78), genotype DR3/DR4 (OR = 19.7), DQA1 * 0301 allele (OR = 4.27), as well as genotype DQA1 * 0301 / DQA1 * 0501 (OR = 13.89) predispose to the development of APS of adults compared to the control group. APS patients were divided into two groups according to the presence of chronic adrenal insufficiency (APS 2 and 4 types - in one group and type 3 APS in the other group). Haplotype DR3-DQ2 (DRB1 * 17-DQA1 * 0501 -DQB1 * 0201) (OR = 2.6), as well as the genotype DR3/DR4 (OR = 4.28) found the strongest association with the development of adrenal insufficiency in patients with APS of adults. Protective haplotypes DRB1 * 01-DQA1 * 0101-DQB1 * 0501 (p<0.01, OR = 0.07), as well as the DRB1 * 01 allele (p<0.01, OR = 0.08) have been identified with respect to the development of adrenal insufficiency in adult APS patients.

CONCLUSION

Examination of patients with APS of adults without chronic adrenal insufficiency for the presence of protective genes for the development of adrenal insufficiency will allow better predicting the risks of developing of the disease within the syndrome.

摘要

目的

探讨成人抗磷脂综合征（APS）患者慢性肾上腺功能不全与Ⅱ类人类白细胞抗原（HLA）基因、细胞毒性T淋巴细胞相关抗原4（CTLA-4）及蛋白酪氨酸磷酸酶非受体型22（PTPN-22）基因多态性之间的关联。

材料与方法

本病例对照研究纳入了78例2型、3型、4型APS患者及109名健康对照者。采用多重引物等位基因特异性聚合酶链反应（PCR）法鉴定Ⅱ类HLA基因、CTLA-4及PTPN-22的等位基因。采用双侧精确Fisher检验进行统计学分析。通过比值比（OR）及95%置信区间（95%CI）评估APS患者慢性肾上腺功能不全的相关性。

结果

与对照组相比，单倍型DR3-DQ2（OR = 4.06）、DR4-DQ8（OR = 5.78）、基因型DR3/DR4（OR = 19.7）、DQA10301等位基因（OR = 4.27）以及基因型DQA10301/DQA10501（OR = 13.89）易导致成人APS的发生。根据是否存在慢性肾上腺功能不全，将APS患者分为两组（2型和4型APS为一组，3型APS为另一组）。单倍型DR3-DQ2（DRB117-DQA10501 -DQB10201）（OR = 2.6）以及基因型DR3/DR4（OR = 4.28）与成人APS患者肾上腺功能不全的发生关联最为密切。已鉴定出对成人APS患者肾上腺功能不全发生具有保护作用的单倍型DRB101-DQA10101-DQB10501（p<0.01，OR = 0.07）以及DRB101等位基因（p<0.01，OR = 0.08）。