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BMC Med Genet. 2019 Dec 21;20(1):201. doi: 10.1186/s12881-019-0903-y.

Vitamin D receptor ApaI polymorphism associated with progression of liver disease in Vietnamese patients chronically infected with hepatitis B virus.

Hoan NX1,2,3,4, Khuyen N5, Giang DP6,7, Binh MT6,8, Toan NL9,10, Anh DT11, Trung NT12,7, Bang MH12,9,8, Meyer CG6,9,13, Velavan TP6,9,13, Song LH14,15,16.

Author information

1
Institute of Clinical Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, 108 Military Central Hospital, Tran Hung Dao Street N1, Hai Ba Trung District, Hanoi, Vietnam. nghiemxuanhoan@gmail.com.
2
Faculty of Tropical and Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam. nghiemxuanhoan@gmail.com.
3
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany. nghiemxuanhoan@gmail.com.
4
Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam. nghiemxuanhoan@gmail.com.
5
Department of Infectious Diseases, Duc Giang Hospital, Hanoi, Vietnam.
6
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
7
Department of Molecular Biology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam.
8
Department of Gastroenterology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam.
9
Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.
10
Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam.
11
Department of Infectious Diseases, 103 Military Hospital, Hanoi, Vietnam.
12
Faculty of Tropical and Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam.
13
Duy Tan University, Da Nang, Vietnam.
14
Institute of Clinical Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, 108 Military Central Hospital, Tran Hung Dao Street N1, Hai Ba Trung District, Hanoi, Vietnam. lehuusong@108-icid.com.
15
Faculty of Tropical and Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam. lehuusong@108-icid.com.
16
Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam. lehuusong@108-icid.com.

Abstract

BACKGROUND:

Vitamin D derivatives and their receptor (VDR) are potent modulators of immune responses in various diseases including malignancies as well as in metabolic and infectious disorders. The impact of vitamin D receptor polymorphisms on clinical outcomes of hepatitis B virus (HBV) infection is not well understood. This study aims to investigate the potential role of VDR polymorphisms (TaqI, FokI, ApaI, and BsmI) in Vietnamese HBV infected patients and to correlate these polymorphisms with the progression of HBV-related liver disease.

METHODS:

Four hundred forty-three HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n = 183), liver cirrhosis (LC, n = 89) and hepatocellular carcinoma (HCC, n = 171) and 238 healthy individuals (HC) were enrolled. VDR polymorphisms were genotyped by DNA sequencing and in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of VDR polymorphisms with manifest HBV infection as well as with progression of related liver diseases mulin different genetic models.

RESULTS:

The VDR ApaI CA genotype was less frequent in HCC than in CHB patients in different genetic models (codominant model, OR = 0.5, 95%CI = 0.3-0.84, P = 0.004; dominant model, OR = 0.46, 95%CI = 0.27-0.76, P = 0.0023). In the recessive model, the genotype ApaI AA was found more frequently among HCC compared to CHB patients (OR = 2.56, 95%CI = 1.01-6.48, P = 0.04). Similarly, the ApaI CA genotype was less frequent in HCC than in non-HCC group codominant model, OR = 0.6, 95%CI = 0.4-0.98, dominant model, P = 0.04 and OR = 0.6, 95%CI = 0.38-0.90, P = 0.017). The ApaI genotypes CA and AA was significantly associated with higher levels of liver enzymes, bilirubin, and HBV DNA (P < 0.05). No association between TaqI, FokI and BsmI polymorphisms and any clinical outcome as well as liver disease progression was found.

CONCLUSIONS:

Among the four investigated VDR polymorphisms, ApaI is associated with clinical outcome and liver disease progression in Vietnamese HBV infected patients.

KEYWORDS:

HBV; Hepatitis B; Liver diseases; Polymorphism; VDR

PMID:
31864292
PMCID:
PMC6925483
DOI:
10.1186/s12881-019-0903-y
[Indexed for MEDLINE]
Free PMC Article

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