ADIPOQ and LEP variants on asthma and atopy: Genetic association modified by overweight
ADIPOQ and LEP variants on asthma and atopy: Genetic association modified by overweight
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DOI：
10.1016/j.gene.2021.145540
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发表时间：
2021-03-08
期刊：
影响因子：
3.5
通讯作者：
Costa, Ryan do Santos
中科院分区：
文献类型：
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作者：
Coelho, Raisa Santos;Melo, Ana Paula Castro;Costa, Ryan do Santos
背景：哮喘和特应性被认为与肥胖相关，受遗传和环境因素的影响。LEP和ADIPOQ基因分别负责瘦素和脂联素的表达和分泌，这些基因的多态性与这两种疾病独立相关，也与高欧洲血统和高收入国家人群中的肥胖相关哮喘表型相关。然而，在混合人群中，很少有研究评估这些变异体对与哮喘和肥胖表型相关的基因的影响。因此，本研究的目的是调查与哮喘和特应性相关的LEP和ADIPOQ的变异，以及超重是否会改变这种影响。研究方法：该研究涉及203名哮喘儿童和813名对照受试者（5至11岁），超重或不超重，来自SCAALA（拉丁美洲哮喘和过敏社会变化）计划。其中，831人有过敏标志物的数据，258名特应性和573名非特应性。基因分型使用商业板Ompelumina 2.5进行。采用PLINK 1.09和三种遗传模型进行Logistic回归分析，以确定预期的关联性：加性、显性和隐性遗传模型，对性别、年龄、蠕虫感染、BMI和主成分（PC）1和2进行了校正，对血统进行了校正，以控制人口结构的混杂因素。结果：ADIPOQ中rs 822396的G等位基因与哮喘的相加模型呈正相关（OR 1.4，95% CI 1.08？rs 1063537的T等位基因在显性模型中的OR值为1.52，95% CI为1.01？2.30）。在LEP中，rs 11763517（C等位基因）和rs 11760956（A等位基因）在相加模型中均与哮喘呈负相关（OR 0.70，95%CI 0.54？0.91; OR 0.66，95% CI 0.50？rs 2167270的A等位基因为显性模型（OR 0.71，95% CI 0.51？0.98）。rs 12706832基因G等位基因在隐性遗传模型中与哮喘发病呈正相关（OR 1.66，95% CI 1.06？2.61）。当按BMI /年龄Z评分对人群进行分层时，观察到的变体rs 11760956、rs 11763517和rs 2167270之间对哮喘的保护作用在超重个体中丧失;观察到的对特应性的保护作用在超重组的所有变体（rs 16861205、rs 2167270和rs 17151919）中丧失。结论：LEP和ADIPOQ基因上的SNPs可能与特应性和哮喘有关。此外，我们还表明，哮喘和特应性保护归因于LEP和ADIPOQ基因的变体是在个人暴露于超重丢失。
Background: Asthma and atopy are considered condition associated with obesity, being affected by genetic and environmental factors. The LEP and ADIPOQ genes, responsible for the expression and secretion of leptin and adiponectin, respectively, and polymorphisms in such genes have been linked to both diseases, independently, and also with the obesity-associated asthma phenotype in populations with high European ancestry and high-income countries. However, in mixed populations, there are few studies evaluating the impact of these vari-ants in genes associated with the phenotype of asthma and obesity. Thus, the aim of this study was to investigate variants in LEP and ADIPOQ associated with asthma and atopy, and whether overweight modifies that effect. Methods: The study involved 203 asthmatics children and 813 control subjects (between 5 and 11 years old), with or without overweight, from the SCAALA (Asthma and Allergy Social Changes in Latin America) program. Among them, 831 had data for allergy markers, being 258 atopic and 573 non-atopic. Genotyping was performed using a commercial panel Omnium Illumina 2.5. Logistic regression was performed to identify associations ex-pected by using PLINK 1.09 and three genetic models: additive, dominant and recessive adjusted for sex, age, helminth infection, BMI and Principal Components (PC) 1 and 2, for ancestry, in order to control the confounding factor by population structure. Results: For asthma, G allele of rs822396, in ADIPOQ, was positively associated in additive model (OR 1.4, 95% CI 1.08?1.83) and T allele of rs1063537 in dominant model (OR 1.52, 95% CI 1.01?2.30). In LEP, rs11763517 (C allele) and rs11760956 (A allele) were both negatively associated with asthma in the additive model (OR 0.70, 95% CI 0.54?0.91; OR 0.66, 95% CI 0.50?0.89) respectively, and the A allele of rs2167270 in dominant model (OR 0.71, 95% CI 0.51?0.98). The G allele of rs12706832 showed a positive association with asthma in the recessive model (OR 1.66, 95% CI 1.06?2.61). When the population was stratified by the BMI / Age Z-Score, the protection observed for asthma between the variants rs11760956, rs11763517 and rs2167270 was lost over-weight individuals; The protection observed for atopy was lost in all variants (rs16861205, rs2167270 and rs17151919) in the overweight group. Conclusion: These results suggest that SNPs on the LEP and ADIPOQ genes may have an impact on atopy and asthma. Furthermore, we also show that the asthma and atopy protection attributed to variants on LEP and ADIPOQ genes is lost in individuals exposed to overweight.