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

Abstract

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

Sero-prevalence of human immunodeficiency virus–hepatitis B virus (HIV–HBV) co-infection among pregnant women attending antenatal care (ANC) in sub-Saharan Africa (SSA) and the associated risk factors: a systematic review and meta-analysis

“…Most importantly however, host genetic factors [ 71 , 72 , 85 ] and the infecting genotypes [ 15 , 73 – 76 ] could be more influential factors in the risk of infection to HBV creating differences and similarities in the burden of HBV–HIV co-infection over a wide ethnic and geographical divide. Among the host genetic factors, polymorphisms in the cytokine promoter gene [ 94 , 95 ] Vitamin D Receptor [ 96 , 97 ] and Human Leucocyte Antigen [ 98 , 99 ] influence the susceptibility to viral infections yet these are individual and population specific [ 94 – 99 ]. Similarly, available evidence has implicated genotype A to be the most prevalent in HBV–HIV co-infection [ 77 ].…”

Controversial Effects of Vitamin D and Related Genes on Viral Infections, Pathogenesis, and Treatment Outcomes

“…In addition, VDR gene polymorphisms were associated with distinct clinical phenotypes in Taiwanese HBV patients [129]. In line with this, VDR ApaI was also associated with the clinical outcome of and liver disease progression in HBV patients [130]. From a therapeutic perspective, VDR rs7975232/ApaI was identified as a pretreatment predictor of sustained HBsAg seroclearance in HBeAg-positive HBV patients when treated with PEG-IFNα [131].…”

Human nuclear receptors (NRs) genes have prognostic significance in hepatocellular carcinoma patients

“…TGF-β induced chemoresistance in liver cancer is modulated by xenobiotic nuclear receptor PXR [ 36 ]. Although there was no association between VDR polymorphisms with HBV infection risk, the ApaI polymorphism might be a genetic factor associated with the clinical outcome and disease progression in HBV infected patients [ 37 ]. Khan et al has also reported that NLRP12 plays a critical role in suppressing the progression of HCC via negative regulation of the JNK pathway [ 38 ].…”