Division of Pediatric Pulmonary Medicine, Allergy and Immunology, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Am J Respir Crit Care Med. 2013 Mar 15;187(6):584-8. doi: 10.1164/rccm.201210-1789OC. Epub 2013 Jan 17.
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.
To examine whether epigenetic or genetic variation in ADCYAP1R1 is associated with childhood asthma in Puerto Ricans.
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 of ADCYAP1R1 (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 in ADCYAP1R1 (rs2267735) and asthma under an additive model. All multivariate models were adjusted for age, sex, household income, and principal components.
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).
Epigenetic and genetic variants in ADCYAP1R1 are associated with asthma in Puerto Rican children.
编码腺苷酸环化酶激活多肽 1（ADCYAP1R1）受体的基因中的表观遗传和/或遗传变异与成年人的创伤后应激障碍和儿童的焦虑有关。社会心理压力与波多黎各儿童的哮喘发病率有关。
研究 ADCYAP1R1 中的表观遗传或遗传变异是否与波多黎各儿童的哮喘有关。
我们对居住在波多黎各圣胡安的 516 名 6-14 岁的儿童进行了病例对照研究。我们使用焦磷酸测序法检测白细胞 DNA 中 ADCYAP1R1 启动子中的 CpG 位点（cg11218385）的甲基化情况。我们使用逻辑回归来检验 cg11218385 甲基化（范围为 0.4-6.1%）是否与哮喘有关。我们还研究了暴力暴露（由儿童 9 岁及以上的暴力暴露量表[ETV]评估）是否与 cg11218385 甲基化（使用线性回归）或哮喘（使用逻辑回归）有关。逻辑回归用于在加性模型下测试 ADCYAP1R1 中的单核苷酸多态性（rs2267735）与哮喘之间的关联。所有多元模型均调整了年龄、性别、家庭收入和主成分。
cg11218385 甲基化每增加 1%，患哮喘的几率就会增加（调整后的比值比，1.3；95%置信区间，1.0-1.6；P=0.03）。在 9 岁及以上的儿童中，暴力暴露与 cg11218385 甲基化有关。单核苷酸多态性 rs2267735 的 C 等位基因与哮喘的发病几率增加显著相关（调整后的比值比，1.3；95%置信区间，1.02-1.67；P=0.03）。
ADCYAP1R1 中的表观遗传和遗传变异与波多黎各儿童的哮喘有关。
