Dataset Information

Human leukocyte antigens and systemic lupus erythematosus: a protective role for the HLA-DR6 alleles DRB113:02 and 14:03.

ABSTRACT: Many studies on associations between human leukocyte antigen (HLA) allele frequencies and susceptibility to systemic lupus erythematosus (SLE) have been performed. However, few protective associations with HLA-DRB1 alleles have been reported. Here, we sought protective, as well as predispositional, alleles of HLA-DRB1 in Japanese SLE patients. An association study was conducted for HLA-DRB1 in Japanese SLE patients. Relative predispositional effects were analyzed by sequential elimination of carriers of each allele with the strongest association. We also explored the association of DRB1 alleles with SLE phenotypes including the presence of autoantibody and clinical manifestations. Significantly different carrier frequencies of certain DRB1 alleles were found to be associated with SLE as follows: increased DRB1*15:01 (P?=?5.48×10?¹?, corrected P (Pc)?=?1.59×10??, odds ratio [OR] 2.17, 95% confidence interval [CI] 1.69-2.79), decreased DRB1*13:02 (P?=?7.17×10??, Pc?=?0.0020, OR 0.46, 95% CI 0.34-0.63) and decreased DRB1*14:03 (P?=?0.0010, Pc?=?0.0272, OR 0.34, 95% CI 0.18-0.63). Additionally, the "*15:01/*13:02 or *14:03" genotype tended to be negatively associated with SLE (P?=?0.4209, OR 0.66), despite there being significant positive associations with *15:01 when present together with alleles other than *13:02 or *14:03 (P?=?1.79×10?¹¹, OR 2.39, 95% CI 1.84-3.10). This protective effect of *13:02 and *14:03 was also confirmed in SLE patients with different clinical phenotypes. To the best of our knowledge, this is the first report of a protective association between the carrier frequencies of HLA-DRB1*13:02 and *14:03 and SLE in the Japanese population.

SUBMITTER: Furukawa H

PROVIDER: S-EPMC3912000 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Human leukocyte antigens and systemic lupus erythematosus: a protective role for the HLA-DR6 alleles DRB113:02 and 14:03.

Furukawa Hiroshi H Kawasaki Aya A Oka Shomi S Ito Ikue I Shimada Kota K Sugii Shoji S Hashimoto Atsushi A Komiya Akiko A Fukui Naoshi N Kondo Yuya Y Ito Satoshi S Hayashi Taichi T Matsumoto Isao I Kusaoi Makio M Amano Hirofumi H Nagai Tatsuo T Hirohata Shunsei S Setoguchi Keigo K Kono Hajime H Okamoto Akira A Chiba Noriyuki N Suematsu Eiichi E Katayama Masao M Migita Kiyoshi K Suda Akiko A Ohno Shigeru S Hashimoto Hiroshi H Takasaki Yoshinari Y Sumida Takayuki T Nagaoka Shouhei S Tsuchiya Naoyuki N Tohma Shigeto S

PloS one 20140203 2

Many studies on associations between human leukocyte antigen (HLA) allele frequencies and susceptibility to systemic lupus erythematosus (SLE) have been performed. However, few protective associations with HLA-DRB1 alleles have been reported. Here, we sought protective, as well as predispositional, alleles of HLA-DRB1 in Japanese SLE patients. An association study was conducted for HLA-DRB1 in Japanese SLE patients. Relative predispositional effects were analyzed by sequential elimination of car ...[more]

PMID: 24498373

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Project description:Background and objectivesTo study human leukocyte antigen (HLA) allele associations in anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis.MethodsA multiethnic cohort of 269 patients with anti-LGI1 encephalitis and 1,359 controls was included. Four-digit HLA sequencing and genome wide association single-nucleotide polymorphism typing imputation (0.99 concordance) were used for HLA typing. Significance of primary and secondary associations was tested using χ2, Fisher exact tests, or logistic regression with the control of population stratification covariates when applicable.ResultsDRB1*07:01 and DQA1*02:01, 2 alleles in strong linkage disequilibrium, were associated with the disease (90% vs 24%, OR = 27.8, p < 10e-50) across ethnicity independent of variation at DRB3 and DQB1, 2 flanking HLA loci. DRB1*07:01 homozygosity was associated with a doubling of risk (OR = 2.1, p = 0.010), suggesting causality. DRB1*07:01 negative subjects were younger (p = 0.003) and more frequently female (p = 0.015). Three patients with malignant thymomas did not carry DRB1*07:01, whereas patients with other tumors had high DRB1*07:01 frequency, suggesting that the presence of tumors other than thymomas may be coincidental and not causal. In both DRB1*07:01 heterozygous individuals and DRB1*07:01 negative subjects, DRB1*04:02 was associated with anti-LGI1 encephalitis, indicating an independent effect of this allele (OR = 6.85, p = 4.57 × 10-6 and OR = 8.93, p = 2.50 × 10-3, respectively). DRB1*04:02 was also independently associated with younger age at onset (β = -6.68, p = 9.78 × 10-3). Major histocompatibility complex peptide-binding predictions using LGI1-derived peptides revealed divergent binding propensities for DRB1*04:02 and DRB1*07:01 alleles, suggesting independent pathogenic mechanisms.DiscussionIn addition to the established primary DRB1*07:01 association in anti-LGI1 encephalitis, we observe a secondary effect of DRB1*04:02 with lower age at onset. Our study provides evidence for secondary effects within HLA locus that correlate with clinical phenotypes in anti-LGI1 encephalitis.

Dataset Information

Human leukocyte antigens and systemic lupus erythematosus: a protective role for the HLA-DR6 alleles DRB113:02 and 14:03.

Publications

Human leukocyte antigens and systemic lupus erythematosus: a protective role for the HLA-DR6 alleles DRB113:02 and 14:03.

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Human leukocyte antigens and systemic lupus erythematosus: a protective role for the HLA-DR6 alleles DRB1*13:02 and *14:03.

Publications

Human leukocyte antigens and systemic lupus erythematosus: a protective role for the HLA-DR6 alleles DRB1*13:02 and *14:03.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Human leukocyte antigens and systemic lupus erythematosus: a protective role for the HLA-DR6 alleles DRB113:02 and 14:03.

Human leukocyte antigens and systemic lupus erythematosus: a protective role for the HLA-DR6 alleles DRB113:02 and 14:03.