Association of a TANK Gene Polymorphism with Outcomes of Hepatitis B Virus Infection in a Chinese Han Population

Abstract

The host genetic compound plays a vital role in determining clinical outcomes of hepatitis B virus (HBV) infection. The tumor necrosis factor receptor-associated factor family member-associated nuclear factor-κB (NF-κB) activator (TANK) takes part in the tumor necrosis factor-α (TNF-α)-mediated NF-κB signaling pathway and the interferon (IFN)-induction pathways that have relevance to HBV-related liver disease. In this report, we explored whether the intronic polymorphism rs3820998 of the TANK gene was associated with outcomes of HBV infection by binary logistic regression analysis. A total of 1305 unrelated Han Chinese patients recruited from Wuhan, including 180 acute-on-chronic hepatitis B liver failure (ACLF-HBV) patients, 331 HBV-related liver cirrhosis (LC) patients, 308 HBV-related hepatocellular carcinoma (HCC) patients, and 486 asymptomatic HBV carriers (AsC) were genotyped using the TaqMan probe method. Logistic analysis revealed that the single-nucleotide polymorphism (SNP) rs3820998 was significantly associated with susceptibility to ACLF-HBV (dominant model, OR 0.643, 95% CI 0.428,0.964, p=0.033; additive model, OR 0.640, 95% CI 0.414,0.990, p=0.045), and LC (recessive model, OR 0.398, 95% CI 0.164,0.966, p=0.042; additive model, OR 0.379, 95% CI 0.155,0.928, p=0.034). These results indicate that the G > T variant is a protective factor in the development of ACLF-HBV and LC, and that the SNP rs3820998 in the TANK gene may play a role in mediating susceptibility to ACLF-HBV and LC in a Chinese Han population.

Genetic variants that associate with cirrhosis have pleiotropic effects on human traits

“…Stage 3 analysis included replicating SNPs as well as SNPs that have been previously reported to associate with cirrhosis in subpopulations, as described in the introduction (Table ) . As above, we included only SNPs with minor allele count >6 in the European populations of UKBB and MGI, which corresponded to minor allele frequency >0.006.…”

“…have been previously reported to associate with cirrhosis in subpopulations, as described in the introduction (Table S1). 5,8,9,[12][13][14][15][16][22][23][24][25][26][27][28][29][30][31][32] As above, we included only SNPs with minor allele count >6 in the European populations of UKBB and MGI, which corresponded to minor allele frequency >0.006. For stage 3 SNPs, a cut-off of P < .05 in either UKBB or MGI was used because there was prior knowledge of their role in liver disease and fibrosis.…”

Association of PNPLA3 rs738409 polymorphism with liver steatosis but not with cirrhosis in patients with HBV infection: Systematic review with meta‐analysis

“…13 Recently, several genetic risk factors, including IL10, TANK, TGFβ1 and PNPLA3 variations, have been determined as genetic triggers for the occurrence of secondary liver complications such as steatosis and cirrhosis. [14][15][16] PNPLA3, which is known as adiponutrin, is located on 22q13 and encodes a 53-kDa protein with 481 amino acids. This protein has triacylglycerol lipase activity.…”

Genome-Wide Association Study of Antiphospholipid Antibodies

“…SESTD1 binds several phospholipid species [8] and may thus serve as an autoantigen for APA. TANK (TRAF family member-associated NFKB activator) is believed to be important in type 1 interferon production [9] and has been suggested to play a role in hepatitis B and C infections [10, 11]. The MYO16 (myosin XVI) locus has recently been implicated in diabetic nephropathy [12–14].…”