Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 15, 2017; 8(6): 304-310
Published online Jun 15, 2017. doi: 10.4239/wjd.v8.i6.304
Interleukin-18 polymorphism as an inflammatory index in metabolic syndrome: A preliminary study
Syeda Sadia Fatima, Zehra Jamil, Syed Hani Abidi, Daniyal Nadeem, Zara Bashir, Ahmed Ansari
Syeda Sadia Fatima, Zehra Jamil, Syed Hani Abidi, Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan, Karachi 74800, Pakistan
Daniyal Nadeem, Zara Bashir, Ahmed Ansari, Medical College, Aga Khan University, Karachi 74800, Pakistan
Author contributions: Fatima SS, Jamil Z and Abidi SH conceived the project, analyzed the data and wrote the paper; Nadeem D, Bashir Z and Ansari A performed the experiments; all authors approved the final version before submission and publication.
Institutional review board statement: This study was approved by the institutional ethical committee and all participants gave a written and informed consent to participate in this study.
Informed consent statement: Informed consent was obtained prior to enrollment from all individual participants included in the study.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: There is no additional data available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Zehra Jamil, Senior Instructor, Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan, Stadium Road, Karachi 74800, Pakistan. zehra.jamil@aku.edu
Telephone: +92-21-34864564 Fax: +92-21-34932494
Received: February 28, 2017
Peer-review started: March 2, 2017
First decision: March 28, 2017
Revised: April 3, 2017
Accepted: April 23, 2017
Article in press: April 24, 2017
Published online: June 15, 2017
Processing time: 106 Days and 8.9 Hours
Abstract
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.

Keywords: Metabolic syndrome, Interleukin-18, Polymorphism, Obesity, Body fat, High density lipoprotein, Low density lipoprotein, Insulin

Core tip: Interleukin-18 (IL-18) gene polymorphisms may influence the expression of its levels. This in turn increases the risk of metabolic syndrome (MetS). Therefore, we aimed to assess the circulatory levels of IL-18 and determine whether the presence of IL-18 promoter polymorphism influences MetS phenotypes. Subjects with AA genotype had a higher body fat, insulin resistance, tumor necrosis factor α and IL-18 levels when compared with subjects with AC (heterozygous) or CC (wild type) genotypes. This preliminary data suggests that IL-18 polymorphism affects IL-18 levels that might cause low grade inflammation. All these increase the susceptibility to develop MetS. Further studies are required to validate our findings.