Effects of STIP1 and GLCCI1 polymorphisms on the risk of childhood asthma and inhaled corticosteroid response in Chinese asthmatic children

Abstract Background Asthma is a common chronic lung disease in children. We aimed to determine the associations between stress-induced phosphoprotein 1 (STIP1) and glucocorticoid-induced transcript 1 (GLCCI1) polymorphisms and susceptibility of childhood asthma and inhaled corticosteroid (ICS) response in children. Methods A total of 263 Chinese Han asthmatic children were recruited from the Xiangya Hospital, Central South University. Pulmonary function tests were performed before the treatment and 3 months after the treatment. One hundred fifty non-asthmatic children were recruited. Each participant’s DNA was extracted from the peripheral blood and Method of MassARRAY was used to genotype the single-nucleotide polymorphisms (SNPs). Results STIP1 rs2236647 wild-type homozygote (CC) was associated with increased asthma risk of children (OR = 1.858, 95% CI:1.205–2.864), but not associated with the ICS response. GLCCI1 rs37969, rs37972 and rs37973 polymorphisms were not associated with the risk of childhood asthma. However, rs37969 mutant genotypes (TT/GT) were significantly associated with less improvement in PD20 (p = 0.028). We also found significant associations between rs37969, rs37972 and rs37973 mutant genotypes and less improvement in maximal midexpiratory flow (MMEF) after ICS treatment for 3 months (p = 0.036, p = 0.010 and p = 0.003, respectively). Conclusions STIP1 rs2236647 was associated with asthma risk of children and GLCCI1 rs37969 mutant genotypes were associated with less improvement in airway hyper-responsiveness. GLCCI1 rs37969, rs37972 and rs37973 polymorphisms might be associated with pulmonary function in childhood asthma patients after ICS treatment.

Download Full-text

Effects of STIP1 and GLCCI1 polymorphisms on the risk of childhood asthma and inhaled corticosteroid response in Chinese asthmatic children

10.21203/rs.2.20489/v2 ◽

2020 ◽

Author(s):

Juan Huang ◽

Xiaolei Hu ◽

Xiangrong Zheng ◽

Jian Kuang ◽

Chentao Liu ◽

...

Keyword(s):

Pulmonary Function ◽

Childhood Asthma ◽

Pulmonary Function Tests ◽

Nucleotide Polymorphisms ◽

Inhaled Corticosteroid ◽

Chinese Han ◽

Asthmatic Children ◽

Asthma Risk ◽

Asthma Patients ◽

Corticosteroid Response

Abstract Background: Asthma is a common chronic lung disease in children. We aimed to determine the associations between stress-induced phosphoprotein 1 (STIP1) and glucocorticoid-induced transcript 1 (GLCCI1) polymorphisms and susceptibility of childhood asthma and inhaled corticosteroid (ICS) response in children. Methods: A total of 263 Chinese Han asthmatic children were recruited from the Xiangya Hospital, Central South University. Pulmonary function tests were performed before the treatment and 3 months after the treatment. 150 non-asthmatic children were recruited. Each participant's DNA was extracted from the peripheral blood and Method of MassARRAY was used to genotype the single-nucleotide polymorphisms (SNPs). Results: STIP1 rs2236647 wild-type homozygote (CC) was associated with increased asthma risk of children (OR=1.858，95% CI：1.205-2.864), but not associated with the ICS response. GLCCI1 rs37969, rs37972 and rs37973 polymorphisms were not associated with the risk of childhood asthma. However, rs37969 mutant genotypes (TT/GT) were significantly associated with less improvement in PD20 (p = 0.028). We also found significant associations between rs37969, rs37972 and rs37973 mutant genotypes and less improvement in maximal midexpiratory flow (MMEF) after ICS treatment for 3 months (p=0.036, p=0.010 and p=0.003, respectively). Conclusions: STIP1 rs2236647 was associated with asthma risk of children and GLCCI1 rs37969 mutant genotypes were associated with less improvement in airway hyper-responsiveness. GLCCI1 rs37969, rs37972 and rs37973 polymorphisms might be associated with pulmonary function in childhood asthma patients after ICS treatment.

Download Full-text

Effects of STIP1 and GLCCI1 polymorphisms on the risk of childhood asthma and inhaled corticosteroid response in Chinese asthmatic children

10.21203/rs.2.20489/v1 ◽

2020 ◽

Author(s):

Juan Huang ◽

Xiaolei Hu ◽

Xiangrong Zheng ◽

Jian Kuang ◽

Chentao Liu ◽

...

Keyword(s):

Pulmonary Function ◽

Childhood Asthma ◽

Early Onset ◽

Pulmonary Function Tests ◽

Nucleotide Polymorphisms ◽

Inhaled Corticosteroid ◽

Chinese Han ◽

Asthmatic Children ◽

Asthma Risk ◽

Increased Risk

Abstract Background: Asthma is a common chronic lung disease in children. We aimed to determine the associations between stress-induced phosphoprotein 1 (STIP1) and glucocorticoid-induced transcript 1 (GLCCI1) polymorphisms and susceptibility of childhood asthma and inhaled corticosteroid (ICS) response in children. Methods: A total of 263 Chinese Han asthmatic children were recruited from the Xiangya Hospital, Central South University. Pulmonary function tests were performed before the treatment and 3 months after the treatment. 150 non-asthmatic children were recruited. Each participant's DNA was extracted from the peripheral blood and Method of MassARRAY was used to genotype the single-nucleotide polymorphisms (SNPs). Results: STIP1 rs2236647 wild-type homozygote (CC) was associated with increased asthma risk of children (OR=1.858，95% CI：1.205-2.864), but not associated with the onset age of asthma and ICS response. GLCCI1 rs37969, rs37972 and rs37973 polymorphisms were not associated with the risk of childhood asthma. However, rs37969 mutant genotypes (TT/GT) were significantly associated with increased risk of early onset asthma (OR=2.254, 95% CI: 1.068-4.757) and less improvement in PD20 (p = 0.028). We also found significant associations between rs37969, rs37972 and rs37973 mutant genotypes and less improvement in maximal midexpiratory flow (MMEF) after ICS treatment for 3 months (p=0.036, p=0.010 and p=0.003, respectively). Conclusions: STIP1 rs2236647 was associated with asthma risk of children. GLCCI1 rs37969 mutant genotypes were associated with increased asthma risk of early onset and less improvement in airway hyper-responsiveness. GLCCI1 rs37969, rs37972 and rs37973 polymorphisms might be associated with pulmonary function in childhood asthma patients after ICS treatment.

Download Full-text

Association of ADAM33 T1 Polymorphism With Subgroups of Pediatric Asthma Patients in Iran

ACTA MEDICA IRANICA ◽

10.18502/acta.v57i11.3259 ◽

2020 ◽

Author(s):

Mir Reza Ghaemi ◽

Sara Hemmati ◽

Arezou Rezaei ◽

Maryam Sadr ◽

Bahareh Mohebbi ◽

...

Keyword(s):

Eosinophil Count ◽

Pulmonary Function Tests ◽

Disease Onset ◽

Pediatric Asthma ◽

Atopic Asthma ◽

Blood Eosinophil ◽

Nucleotide Polymorphisms ◽

Total Blood ◽

Asthma Risk ◽

Asthma Patients

There is strong evidence on the interaction of several genetic variations and environmental conditions in the etiology of asthma. Association of a disintegrin and metalloproteinase 33 (ADAM33) with asthma risk is not clear and shows diversity between nations and ethnicities. Several single nucleotide polymorphisms (SNP) of the ADAM33 gene are introduced and studied according to the disease onset and characteristics. The aim of our study is to determine the association of ADAM33 rs2280091 polymorphism and pediatric asthma in the Iranian population. A total of 63 asthma patients (aged 6-18) and 86 healthy controls were enrolled in our study. Asthma type, classification, and severity were defined. SNPs of the ADAM33 gene at rs2280091 (T1) were analyzed. Pulmonary function tests, total blood eosinophil count, and IgE count were also assessed. T1 genotype and allele frequencies were not associated with asthma risk in Iranian pediatric asthma. Atopic asthma subgroup and patients with normal eosinophil count showed association with ADAM33 rs2280091. Moreover, asthma patients with AG genotype showed lower pulmonary functions.

Download Full-text

Household mold exposure interacts with inflammation-related genetic variants on childhood asthma: a case–control study

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01484-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yu Zhang ◽

Li Hua ◽

Quan-Hua Liu ◽

Shu-Yuan Chu ◽

Yue-Xin Gan ◽

...

Keyword(s):

Childhood Asthma ◽

Case Control Study ◽

Additive Model ◽

Case Control ◽

Nucleotide Polymorphisms ◽

Additive Interaction ◽

Asthmatic Children ◽

Gene Environment ◽

Mold Exposure ◽

Control Study

Abstract Background A number of studies have examined the association between mold exposure and childhood asthma. However, the conclusions were inconsistent, which might be partly attributable to the lack of consideration of gene function, especially the key genes affecting the pathogenesis of childhood asthma. Research on the interactions between genes and mold exposure on childhood asthma is still very limited. We therefore examined whether there is an interaction between inflammation-related genes and mold exposure on childhood asthma. Methods A case–control study with 645 asthmatic children and 910 non-asthmatic children aged 3–12 years old was conducted. Eight single nucleotide polymorphisms (SNPs) in inflammation-related genes were genotyped using MassARRAY assay. Mold exposure was defined as self-reported visible mold on the walls. Associations between visible mold exposure, SNPs and childhood asthma were evaluated using logistic regression models. In addition, crossover analyses were used to estimate the gene-environment interactions on childhood asthma on an additive scale. Results After excluding children without information on visible mold exposure or SNPs, 608 asthmatic and 839 non-asthmatic children were included in the analyses. Visible mold exposure was reported in 151 asthmatic (24.8%) and 119 non-asthmatic children (14.2%) (aOR 2.19, 95% CI 1.62–2.97). The rs7216389 SNP in gasdermin B gene (GSDMB) increased the risk of childhood asthma with each C to T substitution in a dose-dependent pattern (additive model, aOR 1.32, 95% CI 1.11–1.57). Children carrying the rs7216389 T allele and exposed to visible mold dramatically increased the risk of childhood asthma (aOR 3.21; 95% CI 1.77–5.99). The attributable proportion due to the interaction (AP: 0.47, 95% CI 0.03–0.90) and the relative excess risk due to the interaction (RERI: 1.49, 95% CI 0–2.99) were statistically significant. Conclusions In the present study, there was a significant additive interaction between visible mold exposure and rs7216389 SNP on childhood asthma. Future studies need to consider the gene-environment interactions when exploring the risk factors of childhood asthma.

Download Full-text

Polymorphisms in the airway epithelium related genes CDHR3 and EMSY are associated with asthma susceptibility

10.21203/rs.3.rs-31705/v3 ◽

2020 ◽

Author(s):

Miao-miao Zhang ◽

Guo Chen ◽

Yu Wang ◽

Shou quan Wu ◽

Andrew J Sandford ◽

...

Keyword(s):

Airway Epithelium ◽

Association Studies ◽

Chinese Han Population ◽

Binary Logistic Regression Analysis ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Han Population ◽

Asthma Susceptibility ◽

Asthma Risk

Abstract Background: As a main line of defense of the respiratory tract, the airway epithelium plays an important role in the pathogenesis of asthma. CDHR3 and EMSY were reported to be expressed in the human airway epithelium. Although previous genome-wide association studies found that the two genes were associated with asthma susceptibility, similar observations have not been made in the Chinese Han population. Methods: A total of 300 asthma patients and 418 healthy controls unrelated Chinese Han individuals were enrolled. Tag-single nucleotide polymorphisms (Tag-SNPs) were genotyped and the associations between SNPs and asthma risk were analyzed by binary logistic regression analysis. Results: After adjusting for confounding factors, the A allele of rs3847076 in CDHR3 was associated with increased susceptibility to asthma (OR = 1.407, 95% CI: 1.030-1.923). For the EMSY gene, the T alleles of both rs2508746 and rs12278256 were related with decreased susceptibility to asthma (additive model: OR = 0.718, 95% CI: 0.536-0.961; OR = 0.558, 95% CI: 0.332-0.937, respectively). In addition, the GG genotype of rs1892953 showed an association with increased asthma risk under the recessive model (OR = 1.667, 95% CI: 1.104-2.518) and the GATCTGAGT haplotype in EMSY was associated with reduced asthma risk ( P = 0.037). Conclusions: This study identified novel associations of rs3847076 in CDHR3 , as well as rs1892953, rs2508746 and rs12278256 in EMSY with adult asthma susceptibility in the Chinese Han population. Our observations suggest that CDHR3 and EMSY may play important roles in the pathogenesis of asthma in Chinese individuals. Further study with larger sample size is needed.

Download Full-text

Response: Re-examining the use of pulmonary function tests in treatment of acute asthma patients

The Journal of the American Osteopathic Association ◽

10.7556/jaoa.1993.93.11.1082b ◽

1993 ◽

Vol 93 (11) ◽

pp. 1082B

Author(s):

Gilbert E. D'Alonzo

Keyword(s):

Pulmonary Function ◽

Acute Asthma ◽

Pulmonary Function Tests ◽

Function Tests ◽

Asthma Patients

Download Full-text

Polymorphisms in the airway epithelium related genes CDHR3 and EMSY are associated with asthma susceptibility

BMC Pulmonary Medicine ◽

10.1186/s12890-020-01334-0 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Miaomiao Zhang ◽

Guo Chen ◽

Yu Wang ◽

Shou-Quan Wu ◽

Andrew J. Sandford ◽

...

Keyword(s):

Airway Epithelium ◽

Association Studies ◽

Chinese Han Population ◽

Binary Logistic Regression Analysis ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Han Population ◽

Asthma Susceptibility ◽

Asthma Risk

Abstract Background As a main line of defense of the respiratory tract, the airway epithelium plays an important role in the pathogenesis of asthma. CDHR3 and EMSY were reported to be expressed in the human airway epithelium. Although previous genome-wide association studies found that the two genes were associated with asthma susceptibility, similar observations have not been made in the Chinese Han population. Methods A total of 300 asthma patients and 418 healthy controls unrelated Chinese Han individuals were enrolled. Tag-single nucleotide polymorphisms (Tag-SNPs) were genotyped and the associations between SNPs and asthma risk were analyzed by binary logistic regression analysis. Results After adjusting for confounding factors, the A allele of rs3847076 in CDHR3 was associated with increased susceptibility to asthma (OR = 1.407, 95% CI: 1.030–1.923). For the EMSY gene, the T alleles of both rs2508746 and rs12278256 were related with decreased susceptibility to asthma (additive model: OR = 0.718, 95% CI: 0.536–0.961; OR = 0.558, 95% CI: 0.332–0.937, respectively). In addition, the GG genotype of rs1892953 showed an association with increased asthma risk under the recessive model (OR = 1.667, 95% CI: 1.104–2.518) and the GATCTGAGT haplotype in EMSY was associated with reduced asthma risk (P = 0.037). Conclusions This study identified novel associations of rs3847076 in CDHR3, as well as rs1892953, rs2508746 and rs12278256 in EMSY with adult asthma susceptibility in the Chinese Han population. Our observations suggest that CDHR3 and EMSY may play important roles in the pathogenesis of asthma in Chinese individuals. Further study with larger sample size is needed.

Download Full-text

Reduced medication use and improved pulmonary function with supplements containing vegetable and fruit concentrate, fish oil and probiotics in asthmatic school children: a randomised controlled trial

British Journal Of Nutrition ◽

10.1017/s0007114512004692 ◽

2012 ◽

Vol 110 (1) ◽

pp. 145-155 ◽

Cited By ~ 20

Author(s):

Shu-Chen Lee ◽

Yao-Hsu Yang ◽

Shao-Yuan Chuang ◽

Shih-Yi Huang ◽

Wen-Harn Pan

Keyword(s):

Pulmonary Function ◽

Fish Oil ◽

Asthma Control ◽

Childhood Asthma ◽

Test Score ◽

Medication Use ◽

Control Test ◽

Asthma Control Test ◽

Asthmatic Children ◽

Supplement Group

Dietary pattern changes may be one of the key factors associated with increasing asthma prevalence. Observational studies have found negative associations between fruit, vegetable and fish consumption and risk of asthma. Experimental studies have also shown that probiotics can modulate the immune system. However, each dietary component exhibits a modest effect. The objective of the present study was to investigate the joint effect of multiple beneficial dietary components on asthma. We designed a 16-week school-based double-blind placebo-controlled randomised trial. The supplement group received fruit plus vegetable concentrate, fish oil and probiotics (FVFP supplement), while the control group received placebos. A total of 192 asthmatic children aged 10–12 years were recruited from elementary schools in metropolitan Taipei. Pulmonary function, medication usage, Paediatric Asthma Quality of Life Questionnaire (PAQLQ) score and the Childhood Asthma Control Test score were evaluated at baseline, and at weeks 8 and 16. Compared with the placebo group, the supplement group showed significant improvement in pulmonary function parameters (91 v. 178 ml for forced vital capacity (FVC), 40 v. 107 ml for forced expiratory volume in 1 s (FEV1) and 1·6 v. 4·8 % for FEV1:FVC ratio; all P values < 0·01) and had a significantly reduced proportion of those using short-acting inhaled bronchodilators and inhaled corticosteroids. However, the PAQLQ score and the Childhood Asthma Control Test score were not significantly different between the two groups, possibly because the majority of the children were treated routinely. FVFP supplements reduced medication use and improved pulmonary function in asthmatic children. The present study supports an adjuvant intervention with a combination of fruit, vegetable, fish and probiotic foods.

Download Full-text