Dataset Information

Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function.

ABSTRACT:

Background

Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk.

Methods

We included Latino children, adolescents, and young adults aged 8-21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of a PAI-1 gain of function polymorphism and bronchiolitis / Respiratory Syncytial Virus (RSV) or other lower respiratory infections (LRI) within the first 2 years of life on asthma risk, asthma exacerbations and lung function.

Results

RSV infection (OR 9.9, 95%CI 4.9-20.2) and other LRI (OR 9.1, 95%CI 7.2-11.5) were independently associated with asthma, but PAI-1 genotype was not. There were joint effects on asthma risk for both genotype-RSV (OR 17.7, 95% CI 6.3-50.2) and genotype-LRI (OR 11.7, 95% CI 8.8-16.4). A joint effect of genotype-RSV resulted in a 3.1-fold increased risk for recurrent asthma hospitalizations. In genotype-respiratory infection joint effect analysis, FEV1% predicted and FEV1/FVC % predicted were further reduced in the genotype-LRI group (β -2.1, 95% CI -4.0 to -0.2; β -2.0, 95% CI -3.1 to -0.8 respectively). Similarly, lower FEV1% predicted was noted in genotype-RSV group (β -3.1, 95% CI -6.1 to -0.2) with a trend for lower FEV1/FVC % predicted.

Conclusions

A genetic variant of PAI-1 together with early life LRI such as RSV bronchiolitis is associated with an increased risk of asthma, morbidity, and reduced lung function in this Latino population.

SUBMITTER: Cho SH

PROVIDER: S-EPMC4996454 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function.

Cho Seong H SH Min Jin-Young JY Kim Dong Young DY Oh Sam S SS Torgerson Dara R DR Pino-Yanes Maria M Hu Donglei D Sen Saunak S Huntsman Scott S Eng Celeste C Farber Harold J HJ Rodriguez-Cintron William W Rodriguez-Santana Jose R JR Serebrisky Denise D Thyne Shannon M SM Borrell Luisa N LN Williams L Keoki LK DuPont William W Seibold Max A MA Burchard Esteban G EG Avila Pedro C PC Kumar Rajesh R

PloS one 20160824 8

<h4>Background</h4>Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk.<h4>Methods</h4>We included Latino children, adolescents, and young adults aged 8-21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clini ...[more]

PMID: 27556405

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Project description:Changes in dietary patterns may partly explain the epidemic of asthma in industrialized countries. The objective of this study was to examine the relationship between dietary patterns and lung function and asthma exacerbations in Puerto Rican children. This is a case-control study of 678 Puerto Rican children (ages 6-14 years) in San Juan (Puerto Rico). All participants completed a respiratory health questionnaire and a 75-item food frequency questionnaire. Food items were aggregated into 7 groups: fruits, vegetables, grains, protein, dairy, fats, and sweets. Logistic regression was used to evaluate consumption frequency of each group and asthma. Based on the results, a dietary score was created [range from -2 (unhealthy diet: high consumption of dairy and sweets, low consumption of vegetables and grains) to 2 (healthy diet: high consumption of vegetables and grains and low consumption of dairy and sweet)]. Multivariable linear or logistic regression was used to assess the relationship between dietary score and lung function or asthma exacerbations. After adjustment for covariates, a healthier diet (each 1-point increment in dietary score) was associated with significantly higher %predicted forced expiratory volume in the first second (FEV1) and %predicted forced vital capacity (FVC) in control subjects. Dietary pattern alone was not associated with asthma exacerbations, but children with an unhealthy diet and vitamin D insufficiency (plasma 25(OH)D <30 ng/mL) had higher odds of ≥1 severe asthma exacerbation [odds ratio (OR) = 3.4, 95% confidence interval (CI) = 1.5-7.5] or ≥1 hospitalization due to asthma (OR = 3.9, 95% CI = 1.6-9.8, OR = 3.4, 95% CI = 1.5-7.5) than children who ate a healthy diet and were vitamin D sufficient. A healthy diet, with frequent consumption of vegetables and grains and low consumption of dairy products and sweets, was associated with higher lung function (as measured by FEV1 and FVC). Vitamin D insufficiency, together with an unhealthy diet, may have detrimental effects on asthma exacerbations in children.

Dataset Information

Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function.

Background

Methods

Results

Conclusions

Publications

Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function.

Similar Datasets

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