ADCYAP1R1 and Asthma in Puerto Rican Children
ADCYAP1R1 and Asthma in Puerto Rican Children
复制标题
DOI：
10.1164/rccm.201210-1789oc
复制
发表时间：
2013-03-15
影响因子：
24.7
通讯作者：
Celedon, Juan C.
中科院分区：
文献类型：
--
作者：
Chen, Wei;Boutaoui, Nadia;Celedon, Juan C.
理论基础：编码腺苷环化酶激活多肽受体1(ADCYAP1R1)的基因的表观遗传和/或遗传变异与成人的创伤后应激障碍和儿童的焦虑有关。心理社会应激与波多黎各儿童哮喘发病有关。目的：研究ADCYAP1R1基因表观遗传或遗传变异是否与波多黎各儿童哮喘有关。方法：我们对居住在波多黎各圣胡安的516名6-14岁儿童进行了病例对照研究。我们用一种白血球DNA的焦磷酸测序方法评估了ADCYAP1R1(Cg11218385)启动子中CpG位点的甲基化。我们用Logistic回归检验了cg11218385甲基化(范围为0.4-6.1%)是否与哮喘有关。我们还检查了暴力暴露(通过9岁及以上儿童的暴力暴露[ETV]量表进行评估)是否与cg11218385甲基化(使用线性回归)或哮喘(使用Logistic回归)相关。在加性模型下，使用Logistic回归检验ADCYAP1R1(Rs2267735)单核苷酸多态与哮喘的相关性。所有多变量模型都调整了饲料、性别、家庭收入和主成分。测量和主要结果：cg11218385甲基化每增加1%与哮喘发病几率增加相关(调整后的优势比为1.3；95%可信区间为1.0-1.6；P=0.03)。在9岁及以上的儿童中，接触暴力与cg11218385甲基化有关。单核苷酸多态rs2267735的C等位基因与哮喘发病风险显著相关(校正优势比1.3；95%可信区间1.02~1.67；P=0.03)。结论：ADCYAP1R1的表观遗传和遗传变异与波多黎各儿童哮喘相关。
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 in ADCYAP1R1 is 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 of ADCYAP1R1 (cg11218385) using a pyro-sequencing 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 9yr 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 forage, 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 in ADCYAP1R1 are associated with asthma in Puerto Rican children.