Systematic Review of IL-1, IL-4, IL-6, IL-10, IL-15, and IL-18 Gene Polymorphisms and Meta-Analysis of IL-6 Variant and Its Association with Overweight and Obesity Risk in Men

Abstract

Obesity is a complex health risk influenced by genetic, environmental, and lifestyle factors. This review systematically assessed the association between interleukin gene polymorphisms (rs16944, rs17561, rs1143623, rs1143633, rs1143634, rs1800587, rs2234677, and rs4848306), IL-4 (rs180275, rs1805010, IL-6 rs13306435, rs1800795, rs1800796, rs1800797, rs2228145, rs2228145, rs2229238, and rs4845623), IL-10 (rs1518110, rs1518111, rs1800871, rs1800872, rs1800896, rs1878672, rs2834167, rs3024491, rs3024496, rs3024498, and rs3024505), IL-15 (rs3136617, rs3136618, and rs2296135), and IL-18 (rs187238, rs1946518, rs2272127, rs2293225, and rs7559479) and the risk of overweight and obesity in adults, focusing on IL-6 rs1800795 through a meta-analysis. The focus on IL-6 in this review arises from its pleiotropic nature and unclear effect on obesity risk. The review included studies published from 1998 to 2023, sourced from Science Direct, EBSCOhost, Web of Science, and Google Scholar. Bias was assessed with the Cochrane Collaboration tool, and funnel plots were used for publication bias. Results were synthesized into pooled odds ratios (ORs) and confidence intervals (CIs). Thirty studies comprising approximately 29,998 participants were included. The selection criteria required that the articles include participants who were overweight or obese, and this condition needed to be linked to IL polymorphisms. In a meta-analysis, in the dominant model, the pooled OR was 1.26 (95% CI 1.08 to 1.47), indicating those with the GC/CC genotype for IL-6 rs1800795 are 1.26 times more likely to be overweight/obese than GG genotype carriers. For the recessive model, the OR was 1.25 (95% CI 1.04 to 1.51). The overdominant model showed no significant association (OR 1.08, 95% CI 0.94 to 1.25). Interleukin gene variation, particularly the IL-6 rs1800795 variant, is modestly associated with obesity risk. This suggests that other factors, such as the environment, also play a role in obesity. Thus, individuals with this particular IL-6 variant may have a slightly higher likelihood of being overweight or obese compared to those without it, but this is just one of many factors influencing obesity risk.

Keywords: genetic variant; interleukin; obesity; overweight; polymorphism.

Figure 1

PRISMA flow chart for the study selection. Adapted from [17].

Figure 2

Funnel plots displaying the relationship between the effect size of individual studies (x-axis) and their precision, expressed as the inverse of the standard error (y-axis). Each dot represents a single study included in the meta-analysis. The blue dot represents Stephens et al., 2004 [22], purple Wernstedt et al., 2004 [33], red Maculewicz et al., 2021 [23], and black Cimponeriu et al., 2013 [27].

Figure 2

Funnel plots displaying the relationship between the effect size of individual studies (x-axis) and their precision, expressed as the inverse of the standard error (y-axis). Each dot represents a single study included in the meta-analysis. The blue dot represents Stephens et al., 2004 [22], purple Wernstedt et al., 2004 [33], red Maculewicz et al., 2021 [23], and black Cimponeriu et al., 2013 [27].

Figure 3

Risk assessment for the review applying the Cochrane Collaboration tool [17].

Figure 4

A simplified mechanism for the association between interleukin gene polymorphisms and overweight/obesity.

Figure 5

Forest plots of ORs for four articles on the association of IL-6 rs1800795 with BMI in men. (a) GG vs. GC/CC, (b) GG + GC vs. CC, (c) GG + CC vs. GC, (d) GG vs. CC, (e) GG vs. GC, and (f) G vs. C. The grey area’s size indicates the weight of each study and the horizontal lines show the size of the 95% CI. References cited Wernstedt et al., 2004 [33], Maculewicz et al., 2021 [23], Stephens et al., 2004 [22], Cimponeriu et al., 2013 [27].

Figure 5

Forest plots of ORs for four articles on the association of IL-6 rs1800795 with BMI in men. (a) GG vs. GC/CC, (b) GG + GC vs. CC, (c) GG + CC vs. GC, (d) GG vs. CC, (e) GG vs. GC, and (f) G vs. C. The grey area’s size indicates the weight of each study and the horizontal lines show the size of the 95% CI. References cited Wernstedt et al., 2004 [33], Maculewicz et al., 2021 [23], Stephens et al., 2004 [22], Cimponeriu et al., 2013 [27].