Vitamin D receptor gene polymorphisms and distinct clinical phenotypes of hepatitis B carriers in Taiwan

Abstract

Vitamin D exhibits immunomodulatory and antiproliferative effects through vitamin D receptor (VDR) in chronic infections and cancers. We genotyped the BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) polymorphisms of VDR gene in 250 Taiwanese chronic hepatitis B virus (HBV) carriers who were categorized into six phenotypes. After adjustment for age and sex, the frequencies of the VDR B/b, B/a, B/T, B/a/T in patients with hepatitis flare(s) were lower than those without (7 vs 20%, P ¼ 0.009; 1 vs 9%, P ¼ 0.004; 3 vs 10%, P ¼ 0.007; 1 vs 9%, P ¼ 0.005, respectively); in contrast, T/t, A/T, A/t, b/A/t were higher in flare(s) (8 vs 3%, P ¼ 0.003; 49 vs 34%, P ¼ 0.027; 2 vs 1%, P ¼ 0.004; 0.5 vs 0%, P ¼ 0.001, respectively).

Single-Nucleotide Polymorphism at CYP27B1-1260, but Not VDR Taq I, Is Possibly Associated with Persistent Hepatitis B Virus Infection

“…Polymorphisms of VDR may therefore influence the immunomodulation via 1,25(OH) 2 D. There are few studies that have examined the association of VDR polymorphisms with HBV infection. One study indicated that the Bsm I, Apa I, and Taq I polymorphisms of the VDR gene were associated with distinct clinical phenotypes in HBV carriers, but not with HCC development (Huang et al, 2010). An association between the VDR Taq I T allele and asymptomatic hepatitis B was also reported (Shan et al, 2006).…”

“…Single-nucleotide polymorphisms (SNPs) in the VDR gene on chromosome 12q12-q14 have been shown to be associated with distinct clinical phenotypes, except HCC (Huang et al, 2010), and severity of liver disease in HBV infection (Suneetha et al, 2006) with conflicting findings . The CYP27B1-1260 promoter polymorphism has been demonstrated to be associated with autoimmune diseases (Lopez et al, 2004;Bailey et al, 2007;Sundqvist et al, 2010).…”

“…Digested fragments were separated on a 1.5% agarose gel and visualized by ethidium bromide staining. Individuals were determined as homozygous or heterozygous genotypes according to the digestion pattern (Yang and Xiong, 2008;Huang et al, 2010).…”

“…The primers for CYP27B1-1260 were forward 5¢-GTGTTCCCTAAGTGTTGTCTC-3¢; reverse 5¢-GCTGACTC GGTCTCCTCTG-3¢ (Yang and Xiong, 2008). The primers used for the VDR Taq I polymorphism were forward 5¢-CA GAGCATGGACAGGGAGC-3¢; reverse 5¢-AGGAGAGGCA GCGGTACTG-3¢ (Huang et al, 2010). The PCR was performed in a volume of 25-mL reaction containing 12.5 mL (0.3 mg) of 2 · Taq PCR Mix (Xi'an Runde Biotechnology, Xi'an, China), 2 mL genomic DNA (0.05 mg/mL), 1.0 mL (10 mM) of each primer, and 8.5 mL sterile double-distilled water.…”

Recent Updates on Vitamin D and Pediatric Gastrointestinal Diseases

“…Certain polymorphisms in the vitamin D receptor have been associated with occult hepatitis B infection, greater severity of hepatitis B associated liver disease, and a higher viral load [28][29][30][31]. The tumor necrosis factor-alpha (TNF)-α 308 allele and VDR ApaI A allele tend to occur more frequently in children with chronic hepatitis B virus infection, suggesting that the TNF-α and vitamin D pathways may be involved in the susceptibility to and outcome of hepatitis B virus infection acquired early in life [31].…”