HLA-B*27:04 与附着点炎和发病年龄较小相关，以及泰国强直性脊柱炎患者的 HLA-B 等位基因谱：一项横断面研究。

HLA-B*27:04 associated with enthesitis and younger age of onset, and HLA-B allele profile in patients with ankylosing spondylitis in Thailand: A cross-sectional study.

机构信息

Division of Rheumatology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Division of Medical Genetics, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.

出版信息

Int J Rheum Dis. 2021 Mar;24(3):411-417. doi: 10.1111/1756-185X.14055. Epub 2021 Jan 15.

DOI:10.1111/1756-185X.14055

PMID:33448675

Abstract

AIM

The aims of this study were to estimate human leukocyte antigen (HLA)-B allele frequency, to identify alleles associated with ankylosing spondylitis (AS), and to explore manifestations in various HLA-B*27 in Thai AS patients.

METHODS

This was a cross-sectional study. Thai patients older than 18 years with diagnosed AS according to modified New York criteria who visited Siriraj Hospital (Bangkok, Thailand) were consecutively enrolled. HLA-B alleles were determined by reverse sequence-specific oligonucleotide assays, and were assigned at a 4-digit resolution. HLA-B alleles of 334 unrelated healthy Thai donors who participated in a previous phase 2b dengue vaccine clinical trial were included as controls. Odds ratio (OR) and Fisher's exact test were used to estimate association between allele and AS. The P value significance threshold was calculated according to Bonferroni.

RESULTS

Among the 88 patients who were recruited, 34 HLA-B alleles were identified, and all patients were heterozygous. The prevalence of HLA-B27 was 89.8%, and 4 alleles of HLA-B27 were identified. HLA-B27:04 (OR: 39.4, P < .0001) and HLA-B27:05 (OR: 13.8, P = .0011) were associated with AS. In contrast, HLA-B27:06 was not found to be associated with AS (OR: 0.4, P = .241). AS patients carrying HLA-B27:04 were more likely to have enthesitis and younger age at onset than those carrying HLA-B*27:05.

CONCLUSIONS

HLA-B27:04 and HLA-B27:05 were both found to be strongly associated with Thai AS. HLA-B27:06 showed a neutral allele for Thai AS. AS patients with HLA-B27:04 had more enthesitis and younger age at onset than those with HLA-B*27:05.

摘要

目的

本研究旨在估计人类白细胞抗原（HLA）-B 等位基因频率，鉴定与强直性脊柱炎（AS）相关的等位基因，并探讨泰国 AS 患者中不同 HLA-B*27 等位基因的表现。

方法

这是一项横断面研究。连续纳入了年龄大于 18 岁、根据改良纽约标准诊断为 AS 且在泰国 Siriraj 医院就诊的泰国患者。通过反向序列特异性寡核苷酸测定法确定 HLA-B 等位基因，并以 4 位分辨率分配。将之前参加 2b 期登革热疫苗临床试验的 334 名无关健康泰国供体的 HLA-B 等位基因作为对照。使用比值比（OR）和 Fisher 确切检验估计等位基因与 AS 的相关性。根据 Bonferroni 计算 P 值显著性阈值。

结果

在招募的 88 名患者中，共鉴定出 34 个 HLA-B 等位基因，所有患者均为杂合子。HLA-B27 的流行率为 89.8%，鉴定出 4 个 HLA-B27 等位基因。HLA-B27:04（OR：39.4，P<.0001）和 HLA-B27:05（OR：13.8，P=.0011）与 AS 相关。相反，未发现 HLA-B27:06 与 AS 相关（OR：0.4，P=.241）。携带 HLA-B27:04 的 AS 患者比携带 HLA-B*27:05 的患者更易出现附着点炎和发病年龄更小。