Author:
Oka Shomi,Higuchi Takashi,Furukawa Hiroshi,Shimada Kota,Hashimoto Atsushi,Komiya Akiko,Matsui Toshihiro,Fukui Naoshi,Suematsu Eiichi,Ohno Shigeru,Kono Hajime,Katayama Masao,Nagaoka Shouhei,Migita Kiyoshi,Tohma Shigeto
Abstract
AbstractMixed connective tissue disease (MCTD) is a rare systemic autoimmune disease characterized by the production of anti-U1 ribonucleoprotein antibodies and systemic symptoms similar to those of some other autoimmune diseases. HLA-DRB1 polymorphisms are important genetic risk factors for MCTD, but precise associations of DRB1 genotypes with MCTD have not been reported in Japanese people. Genotyping of HLA-DRB1 and -DQB1 was performed in Japanese MCTD patients (n = 116) and controls (n = 413). Associations of specific allele carriers and genotype frequencies with MCTD were analyzed.The following alleles were found to be associated with predisposition to MCTD: HLA-DRB1*04:01 (P = 8.66 × 10–6, Pc = 0.0003, odds ratio [OR] 7.96, 95% confidence interval [CI] 3.13‒20.24) and DRB1*09:01 (P = 0.0189, Pc = 0.5468, OR 1.73, 95% CI 1.12‒2.67). In contrast, the carrier frequency of the DRB1*13:02 allele (P = 0.0032, Pc = 0.0929, OR 0.28, 95% CI 0.11‒0.72) was lower in MCTD patients than in controls. The frequencies of heterozygosity for HLA-DRB1*04:01/*15 (P = 1.88 × 10–7, OR 81.54, 95% CI 4.74‒1402.63) and DRB1*09:01/*15 (P = 0.0061, OR 2.94, 95% CI 1.38‒6.25) were also higher in MCTD patients. Haplotype and logistic regression analyses suggested a predisposing role for HLA-DRB1*04:01, DQB1*03:03, and a protective role for DRB1*13:02. Increased frequencies of HLA-DRB1*04:01/*15 and DRB1*09:01/*15 heterozygous genotypes were found in Japanese MCTD patients.
Funder
Japan Society for the Promotion of Science
National Hospital Organization
Daiwa Securities Health Foundation
Japan Research Foundation for Clinical Pharmacology
The Nakatomi Foundation
Takeda Science Foundation
Mitsui Sumitomo Insurance Welfare Foundation
Bristol-Myers Squibb Co.
the Ministry of Health, Labour, and Welfare of Japan
Japan Agency for Medical Research and Development
Abbott Japan Co., Ltd.
Astellas Pharma Inc.
Chugai Pharmaceutical Co., Ltd.
Eisai Co., Ltd.
Mitsubishi Tanabe Pharma Corporation
Merck Sharp and Dohme Inc.
Pfizer Japan Inc.
Takeda Pharmaceutical Company Limited
Teijin Pharma Limited
Publisher
Springer Science and Business Media LLC