Predisposition of HLA-DRB1*04:01/*15 heterozygous genotypes to Japanese mixed connective tissue disease
Abstract Mixed 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,...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
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Nature Portfolio
2022-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-14116-x |
| _version_ | 1818236906484269056 |
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| author | Shomi Oka Takashi Higuchi Hiroshi Furukawa Kota Shimada Atsushi Hashimoto Akiko Komiya Toshihiro Matsui Naoshi Fukui Eiichi Suematsu Shigeru Ohno Hajime Kono Masao Katayama Shouhei Nagaoka Kiyoshi Migita Shigeto Tohma |
| author_facet | Shomi Oka Takashi Higuchi Hiroshi Furukawa Kota Shimada Atsushi Hashimoto Akiko Komiya Toshihiro Matsui Naoshi Fukui Eiichi Suematsu Shigeru Ohno Hajime Kono Masao Katayama Shouhei Nagaoka Kiyoshi Migita Shigeto Tohma |
| author_sort | Shomi Oka |
| collection | DOAJ |
| description | Abstract Mixed 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. |
| first_indexed | 2024-12-12T12:17:18Z |
| format | Article |
| id | doaj.art-27f6456424f146ffae89b214d1954ff4 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-12T12:17:18Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-27f6456424f146ffae89b214d1954ff42022-12-22T00:24:45ZengNature PortfolioScientific Reports2045-23222022-06-011211910.1038/s41598-022-14116-xPredisposition of HLA-DRB1*04:01/*15 heterozygous genotypes to Japanese mixed connective tissue diseaseShomi Oka0Takashi Higuchi1Hiroshi Furukawa2Kota Shimada3Atsushi Hashimoto4Akiko Komiya5Toshihiro Matsui6Naoshi Fukui7Eiichi Suematsu8Shigeru Ohno9Hajime Kono10Masao Katayama11Shouhei Nagaoka12Kiyoshi Migita13Shigeto Tohma14Department of Clinical Research, National Hospital Organization Tokyo National HospitalDepartment of Clinical Research, National Hospital Organization Tokyo National HospitalDepartment of Clinical Research, National Hospital Organization Tokyo National HospitalDepartment of Rheumatology, National Hospital Organization Sagamihara National HospitalDepartment of Rheumatology, National Hospital Organization Sagamihara National HospitalClinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National HospitalClinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National HospitalClinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National HospitalDepartment of Internal Medicine and Rheumatology, Clinical Research Institute, National Hospital Organization Kyushu Medical CenterCenter for Rheumatic Diseases, Yokohama City University Medical CenterDepartment of Internal Medicine, Teikyo UniversityDepartment of Internal Medicine, National Hospital Organization Nagoya Medical CenterDepartment of Rheumatology, Yokohama Minami Kyosai HospitalClinical Research Center, National Hospital Organization Nagasaki Medical CenterDepartment of Clinical Research, National Hospital Organization Tokyo National HospitalAbstract Mixed 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.https://doi.org/10.1038/s41598-022-14116-x |
| spellingShingle | Shomi Oka Takashi Higuchi Hiroshi Furukawa Kota Shimada Atsushi Hashimoto Akiko Komiya Toshihiro Matsui Naoshi Fukui Eiichi Suematsu Shigeru Ohno Hajime Kono Masao Katayama Shouhei Nagaoka Kiyoshi Migita Shigeto Tohma Predisposition of HLA-DRB1*04:01/*15 heterozygous genotypes to Japanese mixed connective tissue disease Scientific Reports |
| title | Predisposition of HLA-DRB1*04:01/*15 heterozygous genotypes to Japanese mixed connective tissue disease |
| title_full | Predisposition of HLA-DRB1*04:01/*15 heterozygous genotypes to Japanese mixed connective tissue disease |
| title_fullStr | Predisposition of HLA-DRB1*04:01/*15 heterozygous genotypes to Japanese mixed connective tissue disease |
| title_full_unstemmed | Predisposition of HLA-DRB1*04:01/*15 heterozygous genotypes to Japanese mixed connective tissue disease |
| title_short | Predisposition of HLA-DRB1*04:01/*15 heterozygous genotypes to Japanese mixed connective tissue disease |
| title_sort | predisposition of hla drb1 04 01 15 heterozygous genotypes to japanese mixed connective tissue disease |
| url | https://doi.org/10.1038/s41598-022-14116-x |
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