Oncotarget

Research Papers:

Diversity of the association of serum levels and genetic variants of MHC class I polypeptide-related chain A with liver fibrosis in chronic hepatitis C

Chung-Feng Huang, Ching-I Huang, Ming-Lun Yeh, Shu-Chi Wang, Kuan-Yu Chen, Yu-Min Ko, Ching-Chih Lin, Yi-Shan Tsai, Pei-Chien Tsai, Zu-Yau Lin, Shinn-Cherng Chen, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang and Ming-Lung Yu _

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Oncotarget. 2017; 8:32618-32625. https://doi.org/10.18632/oncotarget.15941

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Abstract

Chung-Feng Huang1,2,3, Ching-I Huang1, Ming-Lun Yeh1,2, Shu-Chi Wang1, Kuan-Yu Chen1, Yu-Min Ko1, Ching-Chih Lin1, Yi-Shan Tsai1, Pei-Chien Tsai1, Zu-Yau Lin1,2, Shinn-Cherng Chen1,2, Chia-Yen Dai1,2,3,4, Jee-Fu Huang1,2, Wan-Long Chuang1,2, Ming-Lung Yu1,2,5,6

1Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

2Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

3Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

4Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

5Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

6Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Correspondence to:

Ming-Lung Yu, email: [email protected]

Keywords: MICA, SNP, sMICA, liver fibrosis, CHC

Received: October 15, 2016     Accepted: February 22, 2017     Published: March 06, 2017

ABSTRACT

Background/Aims: Genetic variants of MHC class I polypeptide-related chain A (MICA) at rs2596542 have been associated with hepatocellular carcinoma. The linkage between serum MICA (sMICA) and liver fibrosis in chronic hepatitis C is elusive.

Results: Linear regression analysis revealed that sMICA were independently correlated to α-fetoprotein (β: 0.149; 95% confidence interval [CI]: 0.001, 0.003; P = 0.007)and MICA rs2596542 GG genotype (β: 0.209; 95% CI: 0.153, 0.483; P < 0.001). While patients were stratified by MICA genetic variants, advanced fibrosis was the only factor independently correlated to sMICA among A allele carriers (β: 0.234; 95% CI: 0.107, 0.543; P = 0.004) but not among non-A allele carriers. Logistic regression analysis revealed that factors associated with advanced liver fibrosis was sMICA (OR/CI: 2.996/1.428–6.287, P = 0.004) and platelet counts (OR/CI: 0.988/0.982–0.994, P < 0.001) in MICA rs2596542 A allele carriers. sMICA > 50 pg/mL provided a positive predictive value of 72 % in predicting advanced liver fibrosis (F3-4) and of 90% in significant fibrosis (> F2) in MICA rs2596542 A allele carriers.

Materials and Methods: Serum level and single nucleotide polymorphism at rs2596542 of MICA were tested for the association with liver fibrosis in 319 biopsy proven chronic hepatitis C patients.

Conclusions: Levels of sMICA were highly correlated to liver disease severity in chronic hepatitis C patients who carried the MICA rs738409 A allele. Patients possessing the genetic predisposition had a higher likelihood of progressed liver fibrosis if they expressed higher sMICA levels.


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