Variants in proinflammatory genes IL1RL1, IL1B and IRF4 are associated with overweight in a pediatric Brazilian population

Abstract

Background: Obesity is a chronic complex disease with great prevalence for children all over the world. Characterized for low-grade inflammation associated with several comorbidities such as resistance and type 2 diabetes mellitus (T2DM).

Objectives: To investigate whether genetic variants in IL10, IL1RL1, IL1B, IRF4, TNF, IL6, and IL33 genes are associated with being overweight in children.

Methods: We performed the genotyping of 1004 children using Illumina 2.5 Human Omni bead chip, and association analysis on the genetic variants and the overweight through logistic regression adjusted for sex, age and components principal.

Results: Of the seven genes analyzed, 16 SNVs significantly associated. Eleven variants in IL1RL1, two in IL1B and one in IRF4 genes increased overweight risk and two SNVs in IL1RL1 were associated with protection against overweight. The rs2287047-A was negatively associated (OR: 0.66, CI95%: 0.19-0.45) and had a reduced IL1RL1 expression in whole blood (p 0.033) in silico eQTL. The rs12203592-T, in IRF4, was positively associated with being overweight, and led to an increased gene expression in whole blood (p < 0.001) and adipose tissue (p < 0.001).

Conclusion: These results suggest that genetic variants in inflammatory genes may play an important role in the development of overweight in children.

Keywords: Genetic variants; Overweight; Proinflammatory genes.