Correlation between eosinophil count, its genetic background and body mass index: The Nagahama Study

Sunadome, Hironobu; Matsumoto, Hisako; Izuhara, Yumi; Nagasaki, Tadao; Kanemitsu, Yoshihiro; Ishiyama, Yumi; Morimoto, Chie; Oguma, Tsuyoshi; Ito, Isao; Murase, Kimihiko; Muro, Shigeo; Kawaguchi, Takahisa; Tabara, Yasuharu; Chin, Kazuo; Matsuda, Fumihiko; Hirai, Toyohiro

doi:10.1016/j.alit.2019.05.012

Cited by 41 publications

(38 citation statements)

References 39 publications

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“…This warrants further investigations of IL-17-producing cells in the lung or adipose tissue of obese asthmatics compared to lean asthmatics. Demographic and clinical data for the lean and obese moderate-to-severe asthmatics revealed that lung function was similar in both populations whereas blood eosinophil's were decreased in obese asthmatics, This is in line with previous literature which has shown a negative correlation between BMI and blood eosinophil's in a population with high eosinophil's ( 33 ). The obese asthma phenotype is a complex phenotype where not all obese asthmatics share similar clinical features.…”

Section: Discussionsupporting

confidence: 90%

Contribution of IL-17 in Steroid Hyporesponsiveness in Obese Asthmatics Through Dysregulation of Glucocorticoid Receptors α and β

et al. 2020

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Obesity is on the rise worldwide and is one of the most common comorbidities of asthma. The chronic inflammation seen in obesity is believed to contribute to this process. Asthma and obesity are associated with a poorer prognosis, more frequent exacerbations, and poor asthma control to standard controller medication. Difficult-to-treat asthma is associated with increased levels of Th17 cytokines which have been shown to play a central role in the upregulation of glucocorticoid receptor-beta (GR-β), a dominant-negative inhibitor of the classical GR-α. In this study, we studied the role of IL-17 cytokines in steroid hyporesponsiveness in obese asthmatics. We stimulated lean and obese adipocytes with IL-17A and IL-17F. Adipocytes obtained from obese patients cultured in vitro in the presence of IL-17A for 48 h showed a decrease in GRα/GRβ ratio as compared to adipocytes from lean subjects where GR-α/GR-β ratio was increased following IL-17A and IL-17F stimulation. At protein level, GR-β was increased in obese adipocytes with IL-17A and IL-17F stimulation. IL-8 and IL-6 expression was increased in IL-17-stimulated obese adipocytes. Pre-incubation with Dexamethasone (Dexa) led to a decrease in GR-α/GR-β ratio in obese adipocytes which was further affected by IL-17A whereas Dexa led to an increase in GR-α/GR-β ratio in lean adipocytes which was decreased in response to IL-17A. TGF-β mRNA expression was decreased in obese adipocytes in response to Th17 cytokines. We next sought to validate these findings in obese asthmatic patients. Serum obtained from obese asthmatic subjects showed a decrease in GRα/GRβ protein expression with an increase in IL-17F and IL-13 as compared to serum obtained from non-obese asthmatics. In conclusion, steroid hyporesponsiveness in obese asthmatic patients can be attributed to Th17 cytokines which are responsible for the dysregulation of the GRα/GRβ ratio and the inflammatory response.

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Section: Discussionsupporting

confidence: 90%

Contribution of IL-17 in Steroid Hyporesponsiveness in Obese Asthmatics Through Dysregulation of Glucocorticoid Receptors α and β

et al. 2020

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“…The associated traits are eosinophil counts and high light scatter reticulocyte counts (Astle et al). MYO3A associations with interleukin-6, cortisol secretion, and BMI-adjusted waist circumference have previously been reported [35]; in other studies, eosinophil counts and characteristics of red blood cells have been correlated with obesity or BMI [36,37], and obesity is associated with an inflammatory response [38,39]. Therefore, a true colocalization between the tibial nerve MYO3A eQTL and traits related to properties of immature red blood cells and white blood cells is plausible.…”

Section: Different Eqtl Ancestry Adjustments Yield Minor Differences mentioning

confidence: 86%

Impact of admixture and ancestry on eQTL analysis and GWAS colocalization in GTEx

et al. 2020

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Background Population structure among study subjects may confound genetic association studies, and lack of proper correction can lead to spurious findings. The Genotype-Tissue Expression (GTEx) project largely contains individuals of European ancestry, but the v8 release also includes up to 15% of individuals of non-European ancestry. Assessing ancestry-based adjustments in GTEx improves portability of this research across populations and further characterizes the impact of population structure on GWAS colocalization. Results Here, we identify a subset of 117 individuals in GTEx (v8) with a high degree of population admixture and estimate genome-wide local ancestry. We perform genome-wide cis-eQTL mapping using admixed samples in seven tissues, adjusted by either global or local ancestry. Consistent with previous work, we observe improved power with local ancestry adjustment. At loci where the two adjustments produce different lead variants, we observe 31 loci (0.02%) where a significant colocalization is called only with one eQTL ancestry adjustment method. Notably, both adjustments produce similar numbers of significant colocalizations within each of two different colocalization methods, COLOC and FINEMAP. Finally, we identify a small subset of eQTL-associated variants highly correlated with local ancestry, providing a resource to enhance functional follow-up. Conclusions We provide a local ancestry map for admixed individuals in the GTEx v8 release and describe the impact of ancestry and admixture on gene expression, eQTLs, and GWAS colocalization. While the majority of the results are concordant between local and global ancestry-based adjustments, we identify distinct advantages and disadvantages to each approach.

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“…Sunadome et al. found that blood eosinophils are correlated with BMI up to a plateau of 40 kg/m 2 23 . Likewise, Moussa et al.…”

Section: Evidence That Eosinophils Do Not Reduce Obesitymentioning

confidence: 92%

“…In contrast to mice, human studies have not supported a protective role for eosinophils in obesity. Eosinophilia coexists with obesity, as several small epidemiological studies have demonstrated a positive correlation between blood eosinophil counts and body mass index (BMI) or metabolic syndrome 21–23 . Sunadome et al.…”

Section: Evidence That Eosinophils Do Not Reduce Obesitymentioning

confidence: 99%

Unraveling the connection between eosinophils and obesity

Calco

Fryer

Nie

2020

Journal of Leukocyte Biology

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Obesity affects more than 650 million adults worldwide and is a major risk factor for a variety of serious comorbidities. The prevalence of obesity has tripled in the past forty years and continues to rise. Eosinophils have recently been implicated in providing a protective role against obesity. Decreasing eosinophils exacerbates weight gain and contributes to glucose intolerance in high fat diet‐induced obese animals, while increasing eosinophils prevents high‐fat diet‐induced adipose tissue and body weight gain. Human studies, however, do not support a protective role for eosinophils in obesity. More recent animal studies have also reported conflicting results. Considering these contradictory findings, the relationship between eosinophils and obesity may not be unidirectional. In this mini‐review, we summarize a recent debate regarding the role of adipose tissue eosinophils in metabolic disorders, and discuss local and systemic effects of eosinophils in obesity. Given that adipose eosinophils play a role in tissue homeostasis, more research is needed to understand the primary function of adipose tissue eosinophils in their microenvironment. Therapeutic interventions that target eosinophils in adipose tissue may have the potential to reduce inflammation and body fat, while improving metabolic dysfunction in obese patients.

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Correlation between eosinophil count, its genetic background and body mass index: The Nagahama Study

Cited by 41 publications

References 39 publications

Contribution of IL-17 in Steroid Hyporesponsiveness in Obese Asthmatics Through Dysregulation of Glucocorticoid Receptors α and β

Contribution of IL-17 in Steroid Hyporesponsiveness in Obese Asthmatics Through Dysregulation of Glucocorticoid Receptors α and β

Impact of admixture and ancestry on eQTL analysis and GWAS colocalization in GTEx

Unraveling the connection between eosinophils and obesity

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