Genetic loci for lung function in Japanese adults with adjustment for exhaled nitric oxide levels as airway inflammation indicator

Yamada, Mitsuhiro; Motoike, Ikuko N.; Kojima, Kazuyuki; Fuse, Nobuo; Hozawa, Atsushi; Kuriyama, Shinichi; Katsuoka, Fumiki; Tadaka, Shu; Shirota, Matsuyuki; Sakurai, Miyuki; Nakamura, Tomohiro; Hamanaka, Yohei; Suzuki, Kichiya; Sugawara, Junichi; Ogishima, Soichi; Uruno, Akira; Fujino, Naoya; Numakura, Tadahisa; Ichikawa, Tomohiro; Mitsune, Ayumi; Ohe, Takashi; Kinoshita, Kengo; Ichinose, Masakazu; Sugiura, Hiroaki; Yamamoto, Masayuki

doi:10.1038/s42003-021-02813-8

Cited by 21 publications

(13 citation statements)

References 72 publications

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“…[40] NOS2, a nitric oxide synthase gene, is strongly correlated with the levels of fractional exhaled nitric oxide which is a marker of airway inflammation in asthma. [41,42] And ferroptosis can induce the expression of NOS2 in macrophages, Th2 cytokines can induce the expression of NOS2 either. [43] In some studies, [44] MEF2C knockout enhanced the effect of ferroptosis inducer Erastin on meningioma cell ferroptosis and lipid peroxidation in vitro, and strengthened the meningioma growth inhibition mediated by ferroptosis in mouse models, this may be related to the downregulation of NF2 and E-cadherin.…”

Section: Discussionmentioning

confidence: 99%

The role of ferroptosis-related genes in airway epithelial cells of asthmatic patients based on bioinformatics

2023

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It has been reported that airway epithelial cells and ferroptosis have certain effect on asthma. However, the action mechanism of ferroptosis-related genes in airway epithelial cells of asthmatic patients is still unclear. Firstly, the study downloaded the GSE43696 training set, GSE63142 validation set and GSE164119 (miRNA) dataset from the gene expression omnibus database. 342 ferroptosis-related genes were downloaded from the ferroptosis database. Moreover, differentially expressed genes (DEGs) between asthma and control samples in the GSE43696 dataset were screened by differential analysis. Consensus clustering analysis was performed on asthma patients to classify clusters, and differential analysis was performed on clusters to obtain inter-cluster DEGs. Asthma-related module was screened by weighted gene co-expression network analysis. Then, DEGs between asthma and control samples, inter-cluster DEGs and asthma-related module were subjected to venn analysis for obtaining candidate genes. The last absolute shrinkage and selection operator and support vector machines were respectively applied to the candidate genes to screen for feature genes, and functional enrichment analysis was performed. Finally, a competition endogenetic RNA network was constructed and drug sensitivity analysis was conducted. There were 438 DEGs (183 up-regulated and 255 down-regulated) between asthma and control samples. 359 inter-cluster DEGs (158 up-regulated and 201 down-regulated) were obtained by screening. Then, the black module was significantly and strongly correlated with asthma. The venn analysis yielded 88 candidate genes. 9 feature genes (NAV3, ITGA10, SYT4, NOX1, SNTG2, RNF182, UPK1B, POSTN, SHISA2) were screened and they were involved in proteasome, dopaminergic synapse etc. Besides, 4 mRNAs, 5 miRNAs, and 2 lncRNAs collectively formed competition endogenetic RNA regulatory network, which included RNF182-hsa-miR-455-3p-LINC00319 and so on. The predicted therapeutic drug network map contained NAV3-bisphenol A and other relationship pairs. The study investigated the potential molecular mechanisms of NAV3, ITGA10, SYT4, NOX1, SNTG2, RNF182, UPK1B, POSTN, SHISA2 in airway epithelial cells of asthmatic patients through bioinformatics analysis, providing a reference for the research of asthma and ferroptosis.

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Section: Discussionmentioning

confidence: 99%

The role of ferroptosis-related genes in airway epithelial cells of asthmatic patients based on bioinformatics

2023

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“…These samples were divided into six batches for genotyping, QC, and imputation. Details of those processes have been described in previous studies ( 92 ). The number of SNPs used for imputation in each batch is listed in table S2.…”

Section: Methodsmentioning

confidence: 99%

Genetic architecture of alcohol consumption identified by a genotype-stratified GWAS and impact on esophageal cancer risk in Japanese people

Koyanagi,

Nakatochi,

Namba

et al. 2024

Sci. Adv.

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An East Asian–specific variant on aldehyde dehydrogenase 2 ( ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci ( GCKR , KLB , and ADH1B ) in wild-type homozygotes and six ( GCKR , ADH1B , ALDH1B1 , ALDH1A1 , ALDH2 , and GOT2 ) in heterozygotes, with five showing genome-wide significant interaction with rs671. Genetic correlation analyses revealed ancestry-specific genetic architecture in heterozygotes. Of the discovered loci, four ( GCKR , ADH1B , ALDH1A1 , and ALDH2 ) were suggested to interact with rs671 in the risk of esophageal cancer, a representative alcohol-related disease. Our results identify the genotype-specific genetic architecture of alcohol consumption and reveal its potential impact on alcohol-related disease risk.

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“…The details have been published elsewhere [26,27]. In brief, this cohort study was aimed to contribute to the development of personalized healthcare and medicine worldwide, for which many genomic and epidemiological studies have been conducted [26][27][28][29][30][31][32][33]. To recruit participants, we used three approaches: a type 1 survey (40 433 participants) was conducted at specific municipal health check-up sites; an additional type 1 survey (664 participants) was conducted on different dates at specific municipal health check-ups; and a type 2 survey (13 855 participants) was conducted at a community support center.…”

Section: Study Design and Populationmentioning

confidence: 99%

Association between lung function and hypertension and home hypertension in a Japanese population: the Tohoku Medical Megabank Community-Based Cohort Study

Takase

Yamada

Nakamura

et al. 2023

Journal of Hypertension

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Background: Although several studies have shown an inverse association between lung function and hypertension, few studies have examined the association between lung function and hypertension among never-smokers, and no study has investigated the association between lung function and home hypertension. We investigated the associations between lung function and hypertension in a Japanese population. Individuals and methods: We conducted a cross-sectional study of 3728 men and 8795 women aged 20 years or older living in Miyagi Prefecture, Japan. Lung function was assessed using forced expiratory volume at 1 s (FEV 1 ) and forced vital capacity (FVC), measured by spirometry. Hypertension was defined as a casual blood pressure at least 140/90 mmHg and/or self-reported treatment for hypertension. Home hypertension was defined as morning home blood pressure at least 135/85 mmHg and/or self-reported treatment for hypertension. Multivariate logistic regression models adjusted for potential confounders were used to assess the association between lung function and hypertension. Results: The mean ages (±SD) of men and women were 60.1 (±14.0) years and 56.2 (±13.4) years, respectively, and 1994 (53.5%) men and 2992 (34.0%) women had hypertension. In the multivariable models, FEV 1 and FVC were inversely associated with hypertension. Inverse associations between lung function and hypertension were observed even among never-smokers. Furthermore, reduced lung function was associated with higher prevalence of home hypertension in men and women. Conclusion: Reduced lung function was associated with higher prevalence of hypertension, independent of smoking status. Assessment of the lung function or blood pressure may be required in individuals with reduced lung function or hypertension.

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Genetic loci for lung function in Japanese adults with adjustment for exhaled nitric oxide levels as airway inflammation indicator

Cited by 21 publications

References 72 publications

The role of ferroptosis-related genes in airway epithelial cells of asthmatic patients based on bioinformatics

The role of ferroptosis-related genes in airway epithelial cells of asthmatic patients based on bioinformatics

Genetic architecture of alcohol consumption identified by a genotype-stratified GWAS and impact on esophageal cancer risk in Japanese people

Association between lung function and hypertension and home hypertension in a Japanese population: the Tohoku Medical Megabank Community-Based Cohort Study

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