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This research aims to explore the genetic factors contributing to chronic inflammation in obesity and their impact on metabolic complications.

February 19, 2026Biomedicines0 citationsOpen Access

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Elucidating Genetic Drivers of Chronic Inflammation in Obesity

LRLeyla O. Rashidova DSDanila D. Shashnin PZPavel S. Zubeev

Key Points

This research aims to explore the genetic factors contributing to chronic inflammation in obesity and their impact on metabolic complications.
Included 127 individuals divided into patients with obesity and normal weight.
Conducted genotyping of specific polymorphisms using real-time PCR.
Measured plasma levels of 47 cytokines and chemokines via multiplex immunoassay.
Performed cluster analysis to identify distinct patient subpopulations based on inflammatory profiles.
Identified associations between genetic variants and cytokine levels, indicating a range of inflammatory responses.
Polymorphisms COL1A1 and MMP9 linked to favorable inflammatory profiles.
Variants AGTR1 and MTHFR associated with a pro-inflammatory shift.
Discovered distinct patient subpopulations with varying inflammatory signatures.
Found predictive biomarkers such as IL-8 and albumin for body mass index.

Abstract

Background/Objectives: Obesity is characterized by chronic low-grade inflammation, which plays a central role in the development of its metabolic complications. The genetic factors influencing this inflammatory phenotype remain incompletely understood. This study aimed to analyze the associations of functional polymorphisms in genes involved in extracellular matrix remodeling (MMP2, MMP9, MMP12, COL1A1), metabolism (MTHFR, CYP3A5), and vascular regulation (NOS3, AGTR1) with plasma cytokine profiles and to identify inflammatory subphenotypes in patients with obesity. Methods: The study included 127 individuals, comprising 73 patients with excess body weight (body mass index, BMI ≥ 25 kg/m2) and 54 individuals with normal weight (BMI 18.5–24.9 kg/m2). Genotyping of selected polymorphisms was performed using real-time PCR. Plasma concentrations of 47 cytokines and chemokines were measured by multiplex immunoassay. Results: Nominally significant associations between genetic variants and cytokine levels were identified. Polymorphisms COL1A1 rs1107946 (CA genotype) and MMP9 rs17576 (AG genotype) were associated with a favorable inflammatory profile (decreased IL-6 and increased IL-10, respectively). In contrast, the AGTR1 rs5186 (AC genotipe) variant was associated with elevated TNF-α, IP-10/CXCL10, while the MTHFR rs1801131 (AC genotipe) variant was linked to increased MIP-1β/CCL4, both reflecting a pro-inflammatory shift. Complex, pleiotropic associations were observed for MMP2 rs243865 (elevated IL-7 and Fractalkine/CX3CL1) and NOS3 rs1799983 (elevated MCP-1/CCL2 and Eotaxin/CCL11). Cluster analysis revealed distinct patient subpopulations with differing inflammatory signatures. In one well-defined subgroup, an exploratory model (test R2 = 0.537) identified IL-8, IL-15, and albumin as candidate biomarkers predictive of BMI. Conclusions: The study identifies candidate genetic polymorphisms and inflammatory biomarkers associated with distinct patterns of systemic inflammation in obesity. These hypothesis-generating findings underscore the phenotypic heterogeneity of obesity and provide a basis for further research into the stratification of patients by the risk of developing metabolic complications.

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Cite This Study

Rashidova et al. (Tue,) studied this question.

synapsesocial.com/papers/6996a898ecb39a600b3ef87c https://doi.org/https://doi.org/10.3390/biomedicines14020447

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