Case Control Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2017; 23(22): 4047-4053
Published online Jun 14, 2017. doi: 10.3748/wjg.v23.i22.4047
Association of keratin 8/18 variants with non-alcoholic fatty liver disease and insulin resistance in Chinese patients: A case-control study
Rui Li, Xian-Hua Liao, Jun-Zhao Ye, Min-Rui Li, Yan-Qin Wu, Xuan Hu, Bi-Hui Zhong
Rui Li, Xian-Hua Liao, Jun-Zhao Ye, Min-Rui Li, Yan-Qin Wu, Xuan Hu, Bi-Hui Zhong, Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Author contributions: Li R and Liao XH wrote the manuscript and performed the data analysis; Ye JZ designed the research; Li MR, Wu YQ and Hu X performed the research; Zhong BH revised the paper.
Supported by National Natural Science Foundation of China, No. 81670518 and No. 81170392; The Science and Technology Project of Guangdong Province, China, No. 2013B021800290 and No. 2014A020212118; and Guangzhou Science and Technology Innovation Commission, China, No. 201604020155.
Institutional review board statement: The study was reviewed and approved by The First Affiliated Hospital of Sun Yat-Sen University Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: No additional data are 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: Bi-Hui Zhong, MD, PhD, Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road II, Guangzhou 510080, Guangdong Province, China. sophiazhong@medmail.com.cn
Telephone: +86-20-87755766 Fax: +86-20-87332916
Received: January 31, 2017
Peer-review started: February 8, 2017
First decision: February 23, 2017
Revised: March 10, 2017
Accepted: May 4, 2017
Article in press: May 4, 2017
Published online: June 14, 2017
Processing time: 133 Days and 23.2 Hours
Abstract
AIM

To test the hypothesis that K8/K18 variants predispose humans to non-alcoholic fatty liver disease (NAFLD) progression and its metabolic phenotypes.

METHODS

We selected a total of 373 unrelated adult subjects from our Physical Examination Department, including 200 unrelated NAFLD patients and 173 controls of both genders and different ages. Diagnoses of NAFLD were established according to ultrasonic signs of fatty liver. All subjects were tested for population characteristics, lipid profile, liver tests, as well as glucose tests. Genomic DNA was obtained from peripheral blood with a DNeasy Tissue Kit. K8/K18 coding regions were analyzed, including 15 exons and exon-intron boundaries.

RESULTS

Among 200 NAFLD patients, 10 (5%) heterozygous carriers of keratin variants were identified. There were 5 amino-acid-altering heterozygous variants and 6 non-coding heterozygous variants. One novel amino-acid-altering heterozygous variant (K18 N193S) and three novel non-coding variants were observed (K8 IVS5-9A→G, K8 IVS6+19G→A, K18 T195T). A total of 9 patients had a single variant and 1 patient had compound variants (K18 N193S+K8 IVS3-15C→G). Only one R341H variant was found in the control group (1 of 173, 0.58%). The frequency of keratin variants in NAFLD patients was significantly higher than that in the control group (5% vs 0.58%, P = 0.015). Notably, the keratin variants were significantly associated with insulin resistance (IR) in NAFLD patients (8.86% in NAFLD patients with IR vs 2.5% in NAFLD patients without IR, P = 0.043).

CONCLUSION

K8/K18 variants are overrepresented in Chinese NAFLD patients and might accelerate liver fat storage through IR.

Keywords: Keratin; Variant; Non-alcoholic fatty liver disease; Insulin resistance; Chinese population

Core tip: This study presents the first investigation of the association between keratin 8 and 18 (K8/K18) variants and non-alcoholic fatty liver disease (NAFLD) in a Chinese population. We found an increased frequency of variants in NAFLD patients vs controls. We also identified a new amino acid-altering variant of K18. The results demonstrate that keratin variants are overrepresented in Chinese NAFLD patients and might accelerate liver fat storage through insulin resistance.