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Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1.

ABSTRACT: BACKGROUND:Polymorphisms in the endotoxin-mediated TLR4 pathway genes have been associated with asthma and atopy. We aimed to examine how genetic polymorphisms in innate immunity pathways interact with endotoxin to influence asthma risk in children. METHODS:In a previous analysis of 372 children from the Boston Home Allergens and the Connecticut Childhood Asthma studies, 7 SNPs in 6 genes (CARD15, TGFB1, LY96, ACAA1, DEFB1 and IFNG) involved in innate immune pathways were associated with asthma, and 5 SNPs in 3 genes (CD80, STAT4, IRAK2) were associated with eczema. We tested these SNPs for interaction with early life endotoxin exposure (n = 291), in models for asthma and eczema by age 6. RESULTS:We found a significant interaction between endotoxin and a SNP (rs156265) in ACAA1 (p = 0.0013 for interaction). Increased endotoxin exposure (by quartile) showed protective effects for asthma in individuals with at least one copy of the minor allele (OR = 0.39 per quartile increase in endotoxin, 95% CI 0.15 to 1.01). Endotoxin exposure did not reduce the risk of asthma in children homozygous for the major allele. CONCLUSION:Our findings suggest that protective effects of endotoxin exposure on asthma may vary depending upon the presence or absence of a polymorphism in ACAA1.

SUBMITTER: Sordillo JE

PROVIDER: S-EPMC3252252 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1.

Sordillo Joanne E JE Sharma Sunita S Poon Audrey A Lasky-Su Jessica J Belanger Kathleen K Milton Donald K DK Bracken Michael B MB Triche Elizabeth W EW Leaderer Brian P BP Gold Diane R DR Litonjua Augusto A AA

BMC medical genetics 20111208

<h4>Background</h4>Polymorphisms in the endotoxin-mediated TLR4 pathway genes have been associated with asthma and atopy. We aimed to examine how genetic polymorphisms in innate immunity pathways interact with endotoxin to influence asthma risk in children.<h4>Methods</h4>In a previous analysis of 372 children from the Boston Home Allergens and the Connecticut Childhood Asthma studies, 7 SNPs in 6 genes (CARD15, TGFB1, LY96, ACAA1, DEFB1 and IFNG) involved in innate immune pathways were associat ...[more]

PMID: 22151743

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Project description:BackgroundChildhood asthma and allergic diseases are a significant global problem. There are inconsistent findings on the associations of delivery mode, the number of children in the household and breastfeeding with childhood asthma and allergic diseases. We assessed these associations and examined whether breastfeeding modified the effects of neonatal and familial risk factors on childhood asthma and allergic diseases.MethodsA population-based cross-sectional study was conducted in Shanghai, China. A total of 17 primary schools were randomly selected from 13 districts of Shanghai in this study. The International Study of Asthma and Allergies in Childhood questionnaire was adopted to assess the childhood asthma and allergic diseases. Multivariable logistic regression models were used to evaluate the associations between neonatal and familial factors and childhood asthma and allergic diseases, and to examine the modification effects of breastfeeding on the associations assessed.ResultsOf 10,464 primary school children aged 6-11 years, the overall prevalence of childhood asthma, allergic rhinitis, urticaria, food allergy and drug allergy was 13.9, 22.7, 15.3, 8.1 and 4.6%, respectively. Male sex, high socioeconomic status, cesarean section delivery, only one child in the household and having family history of allergy were associated with increased odds ratio (OR) of childhood asthma and allergic diseases while longer breastfeeding duration (> 6 months) was inversely associated with these diseases. Longer breastfeeding duration also attenuated the OR of neonatal and familial risk factors on childhood asthma and allergic diseases. For instance, the adjusted OR of childhood asthma in the group of vaginal delivery and breastfeeding duration > 6 months was lowest (0.78, 95% confidence interval: 0.66, 0.92).ConclusionsLonger breastfeeding duration was inversely associated with childhood asthma and allergic diseases, and also reduced the OR of neonatal and familial risk factors on these diseases. Giving the prevalence of childhood asthma and allergic diseases is rapidly rising across the globe, these findings may have important clinical and public health implications.

Dataset Information

Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1.

Publications

Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1.

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