ADIPOQ and LEP variants on asthma and atopy: Genetic association modified by overweight

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 variants 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.

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 expected 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.

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 overweight individuals; The protection observed for atopy was lost in all variants (rs16861205, rs2167270 and rs17151919) in the overweight group.

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.