Genetic variations in STAT4,C2,HLA-DRB1 and HLA-DQ associated with risk of hepatitis B virus-related liver cirrhosis

Abstract

Recent genome-wide associated studies (GWASs) have revealed several common loci associated with the risk of hepatitis B virus (HBV)- or hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). We selected 15 single nucleotide polymorphisms (SNPs) identified through GWASs on HBV- or HCV-related HCC, and genotyped them in two independent Chinese cohorts of chronic HBV carriers, including 712 LC cases and 2601 controls. The association of each SNP with the risk of HBV-related LC was assessed by meta-analysis of the two cohorts. Of the 12 SNPs reported in HBV-related HCC GWASs, five SNPs (rs7574865 in STAT4, rs9267673 near C2, rs2647073 and rs3997872 near HLA-DRB1 and rs9275319 near HLA-DQ), were found to be significantly associated with the risk of HBV-related LC (rs7574865: P = 1.79 × 10−2, OR = 1.17, 95% CI = 1.03–1.34; rs9267673: P = 4.91 × 10−4, OR = 1.37, 95% CI = 1.15–1.63; rs2647073: P = 3.53 × 10−5, OR = 1.63, 95% CI = 1.29–2.06; rs3997872: P = 4.22 × 10−4, OR = 1.86, 95% CI = 1.32–2.62; rs9275319: P = 1.30 × 10−2, OR = 1.32, 95% CI = 1.06–1.64). However, among the three SNPs associated with the risk of HCV-related HCC in previous GWASs, none of them showed significant association with the risk of HBV-related LC. Our results suggested that genetic variants associated with HBV-related hepatocarcinogenesis may already play an important role in the progression from CHB to LC.

Clinical significance of SNP (rs2596542) in histocompatibility complex class I-related gene A promoter region among hepatitis C virus related hepatocellular carcinoma cases

“…the SNP rs2596542 is not related to progression of HCC from liver cirrhosis. However, rs2596542C allele was observed more frequently in the control group relative to HCC and LC patients indicating that it contributes to decreased risk of HCC, while rs2596542T allele was a risk factor of HCC and LC susceptibility in chronic HCV carriers where, (OR = 2.1, 95% CI = (1.17–3.78), P  = 0.013) and (OR = 1.93, 95% CI(1.07–3.46), P   =  0.027), respectively, as illustrated in Table 3 and this agrees with Al-Qahtani et al [26] and Jiang et al [35]. The T risk allele was more frequent in the patients group (0.521) compared to that of control group (0.351).…”

Human Genetic Determinants of Viral Diseases

“…Further, carriers of the high-risk allele had lower levels of STAT4 in HCC and nontumor tissues compared to other genotypes, and lower STAT4 expression in tumor compared to adjacent normal tissue. This link between STAT4 variation and HBV infection severity has been verified in additional cohorts (69, 71, 76), although the mechanistic role of STAT4 in controlling infection remains under investigation.…”

Associations between STAT Gene Polymorphisms and Psoriasis in Northeastern China

“…This conclusion was confirmed in different autoimmune diseases, including lupus, rheumatoid arthritis, and ankylosing spondylitis [32,36] . rs7574865 has been associated with numerous autoimmune diseases, as well as with psoriasis in our investigation, indicating that the common functional sequences are shared in those autoimmune diseases and that rs7574865 plays an important role in the immune system and may represent a potential target for the treatment of these diseases [4,37] . STAT6 has similarity with other STAT proteins and is one of the most common candidate genes associated with higher levels of IgE [38] .…”