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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Genetic polymorphism in CD14 gene, a co-receptor of TLR4 associated with non-alcoholic fatty liver disease
Shweta Kapil, Ajay Duseja, Bal Krishan Sharma, Bhupesh Singla, Anuradha Chakraborti, Ashim Das, Pallab Ray, Radha K Dhiman, Yogesh Chawla
Shweta Kapil, Ajay Duseja, Bal Krishan Sharma, Bhupesh Singla, Radha K Dhiman, Yogesh Chawla, Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
Anuradha Chakraborti, Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
Ashim Das, Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
Pallab Ray, Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
Author contributions: Kapil S and Duseja A conceived the study, performed all analyses, interpreted data, and prepared the manuscript; Kapil S performed all molecular biological tests; Sharma BK and Singla B assisted with the collection of samples and sequencing data analysis; Chakraborti A and Ray P helped interpret the data and assisted in preparing the manuscript; Das A performed all histological analyses and reviewed the manuscript; Dhiman RK and Chawla Y participated in the study’s design and critically reviewed the manuscript.
Supported by Indian Council of Medical Research (ICMR), New Delhi, No. 5/4/3-7/2009-NCD-II.
Institutional review board statement: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional (PGIMER, Chandigarh) and/or national research committee, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the ethical committee of PGIMER, Chandigarh (Ethics committee No. 7923-1Trg-08/2281 dated 21/1/10).
Informed consent statement: Informed consent was obtained from all individual participants included in the study.
Conflict-of-interest statement: All authors have no conflict of interest.
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. Ajay Duseja, MD, DM, MNAMS, FACG, Department of Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh 160012, India.
ajayduseja@yahoo.co.in
Telephone: +91-172-2756336 Fax: +91-172-2744401
Received: March 31, 2016
Peer-review started: April 6, 2016
First decision: May 30, 2016
Revised: August 3, 2016
Accepted: September 14, 2016
Article in press: September 14, 2016
Published online: November 14, 2016
Processing time: 226 Days and 5.8 Hours
AIM
To evaluate the pathogenic role of toll-like receptor (TLR) gene polymorphisms in patients with non-alcoholic fatty liver disease (NAFLD).
METHODS
Two hundred and fifty subjects (NAFLD = 200, healthy volunteers = 50) underwent polymerase chain reaction and restriction fragment length polymorphism to assess one polymorphism in the toll-like receptor 2 (TLR2) gene (A753G), two polymorphisms in the TLR4 gene (TLR4 Asp299Gly and Thr399Ile allele), and two polymorphisms in the cluster of differentiation 14 (CD14) (C-159T and C-550T) gene, a co-receptor of TLR4. Association of TLR gene polymorphisms with NAFLD and its severity was evaluated by genetic models of association.
RESULTS
On both multiplicative and recessive models of gene polymorphism association, there was significant association of CD14 C (-159) T polymorphism with NAFLD; patients with TT genotype had a 2.6 fold increased risk of developing NAFLD in comparison to CC genotype. There was no association of TLR2 Arg753Gln, TLR4 Asp299Gly, Thr399Ile, and CD14 C (-550) T polymorphisms with NAFLD. None of the TLR gene polymorphisms had an association with histological severity of NAFLD.
CONCLUSION
Patients with CD14 C (-159) T gene polymorphism, a co-receptor of TLR4, have an increased risk of NAFLD development.
Core tip: Our study demonstrated that non-alcoholic fatty liver disease (NAFLD) patients with TT genotype of C (-159) T polymorphism in cluster of differentiation 14 promoter gene have a higher risk of NAFLD development. However, this polymorphism did not affect liver disease severity. We found no association of toll-like receptor (TLR) 2 ARG753, TLR4 (Asp299Gly), TLR4 (Thr399Ile), and CD 14 C/T 550 polymorphisms with the risk of NAFLD development.
