A Pilot Case-Control Study of Obesity as a State of Metaflammation: Association with Toll-Like Receptor 2 (Arg753Gln) Gene Polymorphism

Abstract

Background: Obesity is a worldwide health issue linked to chronic metabolic low-grade inflammation (metaflammation) causing multiple obesity-related comorbid conditions. Several mediators were related to this metaflammatory process. Objectives: To assess the serum levels of leptin, wingless integration site family member 5A (Wnt5a), and tumor necrosis factor-alpha (TNF-α) as markers of obesity-associated metaflammation and investigate their association with toll-like receptors2 (TLR2) gene (Arg753Gln) single nucleotide polymorphism (SNP) among Egyptian females. Methods: This pilot case-control study included 60 females with obesity and 30 matched controls. Serum levels of leptin, Wnt5a, and TNF-α were assessed by ELISA, while TLR2 (Arg753Gln) genotyping was done by PCR-RFLP. The laboratory and anthropometric data of both groups were compared and correlated. Results: Serum leptin, Wnt5a, and TNF-α showed significantly higher levels in females with obesity and a significant increase with higher classes of obesity. They showed positive correlations with each other and with body weight, body mass index, fat mass index, erythrocyte sedimentation rate, and waist and hip circumferences. Only TNF-α and Wnt5a were associated with metabolic syndrome (MetS) among the obesity group, with Wnt5a being the only independent risk factor for MetS. According to TLR2 (Arg753Gln) SNP, the homozygous GG genotype was associated with elevated levels of TNF-α, leptin, and Wnt5a compared to the heterozygous GA genotype, and it was associated with MetS among the obesity group. The frequencies of the heterozygous GA genotype and the A allele were higher among the obesity group without MetS than those with MetS. Conclusion: Serum leptin, Wnt5a, and TNF-α are significantly higher in women with obesity and the A allele of TLR2 (Arg753Gln) SNP is considered protective against MetS among them.