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World J Diabetes. May 15, 2015; 6(4): 642-647
Published online May 15, 2015. doi: 10.4239/wjd.v6.i4.642
Gene-gene, gene-environment, gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines
Amina Nadeem, Sadaf Mumtaz, Abdul Khaliq Naveed, Muhammad Aslam, Arif Siddiqui, Ghulam Mustafa Lodhi, Tausif Ahmad
Amina Nadeem, Department of Physiology, Army Medical College, National University of Sciences and Technology, Islamabad 46000, Pakistan
Sadaf Mumtaz, College of Medicine, Dammam, University of Dammam, Dammam 31451, Kingdom of Saudi Arabia
Abdul Khaliq Naveed, Department of Biochemistry, Islamic International Medical College, Rifah University, Rawalpindi 44000, Pakistan
Muhammad Aslam, Department of Physiology, University of Health Sciences, Lahore 54000, Pakistan
Arif Siddiqui, Department of Physiology, Islamic International Medical College, Rifah University, Rawalpindi 44000, Pakistan
Ghulam Mustafa Lodhi, Department of Physiology, AL-Nafees Medical College, Isra University, Islamabad 46000, Pakistan
Tausif Ahmad, Dean - Faculty of Pharmacy, Margalla College of Pharmacy, Margalla Institute of Health Sciences, Rawalpindi 44000, Pakistan
Author contributions: Nadeem A and Mumtaz S contributed equally to the work, reviewed the literature and wrote the manuscript; Naveed AK and Aslam M contributed intellectual input to manuscript and helped in writing the manuscript; Siddiqui A, Lodhi GM and Ahmad T helped in writing the manuscript.
Conflict-of-interest: The authors declare no conflicts of interest regarding this manuscript.
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. Amina Nadeem, Associate Professor, Department of Physiology, Army Medical College, National University of Sciences and Technology, NUST Campus, H-12, Islamabad 46000, Pakistan. aminanadeem@amcollege.nust.edu.pk
Telephone: +92-321-5231807 Fax: +92-51-9272502
Received: October 31, 2014
Peer-review started: November 1, 2014
First decision: December 26, 2014
Revised: January 29, 2015
Accepted: February 9, 2015
Article in press: February 12, 2015
Published online: May 15, 2015
Abstract

Inflammation plays a significant role in the etiology of type 2 diabetes mellitus (T2DM). The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and beta cell apoptosis in T2DM. Among the recognized markers are interleukin (IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha (TNF-α), C-reactive protein, resistin, adiponectin, tissue plasminogen activator, fibrinogen and heptoglobins. Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance. Many single nucleotide polymorphisms (SNPs) in various genes including those of pro and anti-inflammatory cytokines have been reported as a risk for T2DM. Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups. The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene, gene-environment and gene-nutrient interactions. This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6, TNF-α, resistin and adiponectin in pathogenesis of T2DM.

Keywords: Cytokines, Gene-environment interaction, Diabetes mellitus, Single nucleotide polymorphism, Gene-gene interaction

Core tip: Single nucleotide polymorphisms (SNPs) in inflammatory cytokines play role in insulin resistance and type 2 diabetes mellitus (T2DM). These SNPs are found to be correlated with cytokine serum levels, body mass index, insulin resistance and dyslipidemia although these findings are challenged by other studies. Gene-gene, gene-environment and gene-nutrient interactions alter the impact of these SNPs in pathogenesis of T2DM. These interactions may explain the inter-ethnic variations in role of inflammatory cytokines in T2DM reported in international studies. This mini-review highlights these gene-genes, gene-environment and gene-nutrient interactions and their impact on inflammatory cytokine SNPs.