Hironobu Sunadome1, Hisako Matsumoto2, Yumi Izuhara1, Tadao Nagasaki1, Yoshihiro Kanemitsu3, Yumi Ishiyama1, Chie Morimoto1, Tsuyoshi Oguma1, Isao Ito1, Kimihiko Murase4, Shigeo Muro5, Takahisa Kawaguchi6, Yasuharu Tabara6, Kazuo Chin4, Fumihiko Matsuda6, Toyohiro Hirai1. 1. Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. 2. Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: hmatsumo@kuhp.kyoto-u.ac.jp. 3. Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University School of Medical Sciences, Nagoya, Japan. 4. Department of Respiratory Care and Sleep Control Medicine, Kyoto University, Graduate School of Medicine, Kyoto, Japan. 5. Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Respiratory Medicine, Nara Medical University, Nara, Japan. 6. Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Abstract
BACKGROUND: Obesity affects the pathogenesis of various chronic diseases, including asthma. Research on correlations between obesity/BMI and eosinophilic inflammation in asthma has yielded contradictory results, which could be partly ascribed to the absence of epidemiological data on the correlations. We aimed to elucidate the correlations between blood eosinophil count, its genetic backgrounds, and BMI in the general population. METHODS: This community-based Nagahama study in Japan enrolled 9789 inhabitants. We conducted self-reporting questionnaires, lung function tests, and blood tests in the baseline and 5-year follow-up studies. A genome-wide association study (GWAS) was performed in 4650 subjects at the baseline and in 4206 of these at the follow-up to determine single-nucleotide polymorphisms for elevated blood eosinophil counts. We assessed the correlations between BMI and eosinophil counts using a multifaceted approach, including the cluster analysis. RESULTS: Eosinophil counts positively correlated with BMI, observed upon the interchange of an explanatory variable, except for subjects with the highest quartile of eosinophils (≥200/μL), in whom BMI negatively correlated with eosinophil counts. GWAS and human leukocyte antigen (HLA) imputation identified rs4713354 variant (MDC1 on chromosome 6p21) for elevated eosinophil counts, independent of BMI and IgE. Rs4713354 was accumulated in a cluster characterized by elevated eosinophil counts (mean, 498 ± 178/μL) but normal BMI. CONCLUSIONS: Epidemiologically, there may be a positive association between blood eosinophil counts and BMI in general, but there was a negative correlation in the population with high eosinophil counts. Factors other than BMI, particularly genetic backgrounds, may contribute to elevated eosinophil counts in such populations.
BACKGROUND:Obesity affects the pathogenesis of various chronic diseases, including asthma. Research on correlations between obesity/BMI and eosinophilic inflammation in asthma has yielded contradictory results, which could be partly ascribed to the absence of epidemiological data on the correlations. We aimed to elucidate the correlations between blood eosinophil count, its genetic backgrounds, and BMI in the general population. METHODS: This community-based Nagahama study in Japan enrolled 9789 inhabitants. We conducted self-reporting questionnaires, lung function tests, and blood tests in the baseline and 5-year follow-up studies. A genome-wide association study (GWAS) was performed in 4650 subjects at the baseline and in 4206 of these at the follow-up to determine single-nucleotide polymorphisms for elevated blood eosinophil counts. We assessed the correlations between BMI and eosinophil counts using a multifaceted approach, including the cluster analysis. RESULTS: Eosinophil counts positively correlated with BMI, observed upon the interchange of an explanatory variable, except for subjects with the highest quartile of eosinophils (≥200/μL), in whom BMI negatively correlated with eosinophil counts. GWAS and human leukocyte antigen (HLA) imputation identified rs4713354 variant (MDC1 on chromosome 6p21) for elevated eosinophil counts, independent of BMI and IgE. Rs4713354 was accumulated in a cluster characterized by elevated eosinophil counts (mean, 498 ± 178/μL) but normal BMI. CONCLUSIONS: Epidemiologically, there may be a positive association between blood eosinophil counts and BMI in general, but there was a negative correlation in the population with high eosinophil counts. Factors other than BMI, particularly genetic backgrounds, may contribute to elevated eosinophil counts in such populations.
Authors: Saba Al Heialy; Mellissa Gaudet; Rakhee K Ramakrishnan; Andrea Mogas; Laila Salameh; Bassam Mahboub; Qutayba Hamid Journal: Front Immunol Date: 2020-08-04 Impact factor: 7.561
Authors: Nicole R Gay; Michael Gloudemans; Margaret L Antonio; Nathan S Abell; Brunilda Balliu; YoSon Park; Alicia R Martin; Shaila Musharoff; Abhiram S Rao; François Aguet; Alvaro N Barbeira; Rodrigo Bonazzola; Farhad Hormozdiari; Kristin G Ardlie; Christopher D Brown; Hae Kyung Im; Tuuli Lappalainen; Xiaoquan Wen; Stephen B Montgomery Journal: Genome Biol Date: 2020-09-11 Impact factor: 13.583
Authors: Bradley E Chipps; Nizar Jarjour; William J Calhoun; Ahmar Iqbal; Tmirah Haselkorn; Ming Yang; Jochen Brumm; Jonathan Corren; Cecile T J Holweg; Mona Bafadhel Journal: Ann Am Thorac Soc Date: 2021-12