ADCYAP1R1and Asthma in Puerto Rican Children

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Abstract

Rationale:

Epigenetic and/or genetic variation in the gene encoding the receptor for adenylate-cyclase activating polypeptide 1 (ADCYAP1R1) has been linked to post-traumatic stress disorder in adults and anxiety in children. Psychosocial stress has been linked to asthma morbidity in Puerto Rican children.

Objectives:

To examine whether epigenetic or genetic variation inADCYAP1R1is associated with childhood asthma in Puerto Ricans.

Methods:

We conducted a case-control study of 516 children ages 6-14 years living in San Juan, Puerto Rico. We assessed methylation at a CpG site in the promoter ofADCYAP1R1(cg11218385) using a pyrosequencing assay in DNA from white blood cells. We tested whether cg11218385 methylation (range, 0.4-6.1%) is associated with asthma using logistic regression. We also examined whether exposure to violence (assessed by the Exposure to Violence [ETV] Scale in children 9 yr and older) is associated with cg11218385 methylation (using linear regression) or asthma (using logistic regression). Logistic regression was used to test for association between a single nucleotide polymorphism inADCYAP1R1(rs2267735) and asthma under an additive model. All multivariate models were adjusted for age, sex, household income, and principal components.

Measurements and Main Results:

Each 1% increment in cg11218385 methylation was associated with increased odds of asthma (adjusted odds ratio, 1.3; 95% confidence interval, 1.0-1.6;P= 0.03). Among children 9 years and older, exposure to violence was associated with cg11218385 methylation. The C allele of single nucleotide polymorphism rs2267735 was significantly associated with increased odds of asthma (adjusted odds ratio, 1.3; 95% confidence interval, 1.02-1.67;P= 0.03).

Conclusions:

Epigenetic and genetic variants inADCYAP1R1are associated with asthma in Puerto Rican children.

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