Interleukin-18 polymorphism as an inflammatory index in metabolic syndrome: A preliminary study

AIM To assess circulatory levels of interleukin-18 (IL-18) and determine whether the presence of IL-18 promoter polymorphism influences metabolic syndrome phenotypes. METHODS This study recruited one hundred and eighty individuals divided into three groups with sixty subjects each as: Normal weight (18.0-22.9 kg/m2), overweight (23.0-25.9 kg/m2) and obese (> 26.0 kg/m2) according to South Asian criteria of BMI. Fasting blood glucose (FBG), Lipid profile, insulin, IL-18 and tumor necrosis factor (TNF)α were measured using ELISA kits, whereas low density lipoprotein (LDL)-cholesterol, insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) were calculated. The body fat percentage (BF) was measured through bioelectrical impedance analysis; waist and hip circumference were measured. Genotyping of IL-18 -607 C/A polymorphism was performed by using tetra-primer amplification refractory mutation system. Student t test, One-way analysis of variance, Hardy-Weinberg equilibrium, Pearson's χ2 test and Pearson's correlation were used, where a P value < 0.05 was considered significant. RESULTS In an aged matched study, obese subjects showed higher levels of FBG, cholesterol, triglycerides and LDL levels as compared to normal weight (P < 0.001). Highest levels of IL-18 and TNF levels were also seen in obese subjects (IL-18: 58.87 ± 8.59 ng/L) (TNF: 4581.93 ± 2132.05 pg/mL). The percentage of IL-18 -607 A/A polymorphism was higher in overweight and obese subjects vs normal weight subjects (P < 0.001). Moreover, subjects with AA genotype had a higher BF, insulin resistance, TNFα and IL-18 levels when compared with subjects with AC (heterozygous) or CC (wild type) genotypes. However, we did not find any difference in the lipid profile between three subgroups. CONCLUSION This preliminary data suggests that IL-18 polymorphism affects IL-18 levels that might cause low grade inflammation, further exacerbated by increased TNFα. All these increase the susceptibility to develop MetS. Further studies are required to validate our findings.