Case Control Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Feb 15, 2017; 8(2): 66-73
Published online Feb 15, 2017. doi: 10.4239/wjd.v8.i2.66
Association of NFKB1 gene polymorphism (rs28362491) with levels of inflammatory biomarkers and susceptibility to diabetic nephropathy in Asian Indians
Amar Gautam, Stuti Gupta, Mohit Mehndiratta, Mohini Sharma, Kalpana Singh, Om P Kalra, Sunil Agarwal, Jasvinder K Gambhir
Amar Gautam, Om P Kalra, Sunil Agarwal, Department of Medicine, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Delhi 110095, India
Stuti Gupta, Mohit Mehndiratta, Mohini Sharma, Kalpana Singh, Jasvinder K Gambhir, Molecular Diagnostic Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Delhi 110095, India
Author contributions: Gautam A and Gupta S contributed equally to this article; Gautam A, Gupta S, Sharma M and Singh K performed sample collection, majority of experiments, analyzed data and wrote manuscript; Mehndiratta M, Kalra OP, Agarwal S and Gambhir JK contributed to conceptual and study design, data analysis and interpretation, as well as manuscript writing.
Institutional review board statement: The protocol of the present study was reviewed and approved by Institutional Ethics Committee for Human Research, Delhi University, and UCMS and GTB Hospital, Delhi.
Informed consent statement: Informed consent was obtained from the all recruited subjects. They were briefed on the purpose of the study and its implication prior to donating peripheral blood.
Conflict-of-interest statement: No conflict of interest exists for this study.
Data sharing statement: No data sharing as this manuscript and the data were not published elsewhere.
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: Jasvinder K Gambhir, PhD, Professor, Molecular Diagnostic Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India. jassigambhir@yahoo.co.in
Telephone: +91-98-11641277
Received: September 12, 2016
Peer-review started: September 19, 2016
First decision: October 21, 2016
Revised: December 6, 2016
Accepted: December 27, 2016
Article in press: December 28, 2016
Published online: February 15, 2017
Abstract
AIM

To investigate the association of NFKB1 gene -94 ATTG insertion/deletion (rs28362491) polymorphism with inflammatory markers and risk of diabetic nephropathy in Asian Indians.

METHODS

A total of 300 subjects were recruited (100 each), normoglycemic, (NG); type 2 diabetes mellitus (T2DM) without any complications (DM) and T2DM with diabetic nephropathy [DM-chronic renal disease (CRD)]. Analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism and ELISA. Pearson’s correlation, analysis of variance and logistic regression were used for statistical analysis.

RESULTS

The allelic frequencies of -94 ATTG insertion/deletion were 0.655/0.345 (NG), 0.62/0.38 (DM) and 0.775/0.225 (DM-CRD). The -94 ATTG ins allele was associated with significantly increased levels of urinary monocyte chemoattractant protein-1 (uMCP-1); uMCP-1 (P = 0.026) and plasma tumor necrosis factor-alpha (TNF-α); TNF-α (P = 0.030) and almost doubled the risk of diabetic nephropathy (OR = 1.91, 95%CI: 1.080-3.386, P = 0.025).

CONCLUSION

-94 ATTG ins/ins polymorphism might be associated with increased risk of developing nephropathy in Asian Indian subjects with diabetes mellitus.

Keywords: Diabetic nephropathy, Inflammation, NFKB1 -94 ATTG ins/del polymorphism, Urinary monocyte chemoattractant protein-1, Tumor necrosis factor-alpha

Core tip: Type 2 diabetes mellitus (T2DM) is considered as long standing inflammatory disease. Diabetic nephropathy (DN) is the most common micro-vascular complication of T2DM. Pro-inflammatory cytokines like Monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) plays a crucial role in the pathogenesis of DN. Therefore we investigated -94 ins/del ATTG polymorphism in NFKB1 gene and its association with the risk of DN in Asian Indians. -94 ins/del ATTG single nucleotide polymorphism was found to increase the urinary MCP-1 and plasma TNF-α levels. Our findings open a new area of research to explore that -94 ins/del ATTG may be considered as genetic markers for early detection of diabetic patients who are at greater risk of development of nephropathy.