PMID- 31977282 OWN - NLM STAT- MEDLINE DCOM- 20201110 LR - 20201110 IS - 1544-0591 (Electronic) IS - 0022-0345 (Linking) VI - 99 IP - 3 DP - 2020 Mar TI - A Targeted Genetic Association Study of the Rare Type of Osteomyelitis. PG - 271-276 LID - 10.1177/0022034520901519 [doi] AB - Chronic nonbacterial osteomyelitis is a rare bone disorder that can be found in the jaw. It is often associated with systemic conditions, including autoimmune deficiencies. However, little is known about how the genetic and immunologic background of patients influences the disease. Here, we focus on human leukocyte antigen (HLA), killer cell immunoglobulin-like receptors (KIRs), and their specific combinations that have been difficult to analyze owing to their high diversity. We employed a recently developed technology of simultaneous typing of HLA alleles and KIR haplotype and investigated alleles of the 35 HLA loci and KIR haplotypes composed of centromeric and telomeric motifs in 18 cases and 18 controls for discovery and 472 independent controls for validation. We identified an amino acid substitution of threonine at position 94 of HLA-C in combination with the telomeric KIR genotype of haplotype tA01/tB01 that had significantly higher frequency (>20%) in the case population than in both control populations. Multiple logistic regression analysis based on a dominant model with adjustments for age and sex revealed and validated its statistical significance and high predictive accuracy (C-statistic >/=0.85). Structure-based analysis revealed that the combination of the amino acid change in HLA-C and the telomeric genotype tA01/tB01 could be associated with lower stability of HLA-C. This is the first case-control study of a rare disease that employed the latest sequencing technology enabling simultaneous typing and investigated amino acid polymorphisms at HLA loci in combination with KIR haplotype. FAU - Yahara, H AU - Yahara H AD - Department of Molecular Immunology and Inflammation, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. FAU - Horita, S AU - Horita S AD - Department of Bioregulation and Pharmacological Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan. FAU - Yanamoto, S AU - Yanamoto S AD - Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. FAU - Kitagawa, Y AU - Kitagawa Y AD - Department of Oral Diagnosis and Medicine, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan. FAU - Asaka, T AU - Asaka T AD - Department of Oral Diagnosis and Medicine, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan. FAU - Yoda, T AU - Yoda T AD - Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. FAU - Morita, K AU - Morita K AD - Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. AD - Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan. FAU - Michi, Y AU - Michi Y AD - Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. FAU - Takechi, M AU - Takechi M AD - Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. FAU - Shimasue, H AU - Shimasue H AD - Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. FAU - Maruoka, Y AU - Maruoka Y AD - Department of Oral and Maxillofacial Surgery, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan. FAU - Kondo, E AU - Kondo E AD - Department of Dentistry and Oral Surgery, School of Medicine, Shinshu University, Matsumoto, Japan. FAU - Kusukawa, J AU - Kusukawa J AD - Dental and Oral Medical Center, School of Medicine, Kurume University, Fukuoka, Japan. FAU - Tsujiguchi, H AU - Tsujiguchi H AD - Department of Environmental and Preventive Medicine, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan. FAU - Sato, T AU - Sato T AUID- ORCID: 0000-0001-9866-0346 AD - Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan. FAU - Kannon, T AU - Kannon T AD - Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan. FAU - Nakamura, H AU - Nakamura H AD - Department of Environmental and Preventive Medicine, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan. FAU - Tajima, A AU - Tajima A AUID- ORCID: 0000-0001-6808-5491 AD - Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan. FAU - Hosomichi, K AU - Hosomichi K AD - Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan. FAU - Yahara, K AU - Yahara K AD - Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200124 PL - United States TA - J Dent Res JT - Journal of dental research JID - 0354343 RN - 0 (Receptors, KIR) SB - IM MH - Case-Control Studies MH - Gene Frequency MH - Genetic Association Studies MH - Genotype MH - Haplotypes/genetics MH - Humans MH - *Osteomyelitis/genetics MH - Receptors, KIR/genetics OTO - NOTNLM OT - autoimmune disease OT - case-control study OT - epidemiology OT - human leukocyte antigen OT - jaw disease OT - killer inhibitory receptor EDAT- 2020/01/25 06:00 MHDA- 2020/11/11 06:00 CRDT- 2020/01/25 06:00 PHST- 2020/01/25 06:00 [pubmed] PHST- 2020/11/11 06:00 [medline] PHST- 2020/01/25 06:00 [entrez] AID - 10.1177/0022034520901519 [doi] PST - ppublish SO - J Dent Res. 2020 Mar;99(3):271-276. doi: 10.1177/0022034520901519. Epub 2020 Jan 24.