Marmara University School of Medicine, Division of Gastroenterology and Hepatology, Istanbul; Marmara University, Institute of Gastroenterology, Istanbul; Department of Medical Biology, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey.
Marmara University, Institute of Gastroenterology, Istanbul; Department of Medical Biology, School of Medicine, Recep Tayyip Erdogan University, Rize; Marmara University, School of Medicine, Department of Medical Biology, Istanbul, Turkey.
J Gastrointestin Liver Dis. 2024 Jun 29;33(2):203-211. doi: 10.15403/jgld-5474.
Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral therapy. Presence of single nucleotide polymorphisms (SNPs) such as PNPLA3 rs738409 and TM6SF2 rs58542926 are associated with the development and progression of steatotic liver disease to HCC, whereas a splice variant in HSD17B13 rs72613567:TA has been shown to be protective. We investigated the role of these SNPs in the development or prognosis of HCC in pure CHB etiology, in the absence of hepatic steatosis, remains unknown.
We analysed PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 SNPs in a prospectively recruited cohort (n=323) consisting of healthy controls, CHB and CHB-HCC patients without hepatic steatosis. SNPs were determined by PCR analysis and associations for the alleles and genotypes were investigated using adjusted-logistic regression analyses. The overall survival (OS) data were collected from CHB-HCC patients for survival analysis.
The genotype and allelic distribution of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 were similar between healthy controls, CHB, and CHB-HCC groups. No genotype, allele or haplotype analysis was found to be associated with increased risk for CHB-HCC. Survival analysis revealed no genotype or allele to be associated with OS in patients with CHB-HCC.
We could not demonstrate any association of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 with the development or prognosis of CHB-HCC, supporting the initial hypothesis that they should be considered specific hotspots for liver diseases characterized with hepatic steatosis.
在慢性乙型肝炎（CHB）中，病毒抑制限制了肝细胞癌（HCC）的进展；然而，尽管进行了抗病毒治疗，仍有部分患者病情仍会进展。一些单核苷酸多态性（SNP）如 PNPLA3 rs738409 和 TM6SF2 rs58542926 与脂肪性肝病向 HCC 的发展和进展相关，而 HSD17B13 rs72613567:TA 的剪接变异体则具有保护作用。我们研究了这些 SNP 在单纯 CHB 病因、无肝脂肪变性的 HCC 发展或预后中的作用，目前尚不清楚。
我们分析了前瞻性招募的队列（n=323）中 PNPLA3 rs738409、TM6SF2 rs58542926 和 HSD17B13 rs72613567 的 SNP，该队列由健康对照者、CHB 和无肝脂肪变性的 CHB-HCC 患者组成。通过 PCR 分析确定 SNP，并通过调整后的逻辑回归分析研究等位基因和基因型的关联。收集 CHB-HCC 患者的总生存（OS）数据进行生存分析。
PNPLA3 rs738409、TM6SF2 rs58542926 和 HSD17B13 rs72613567 的基因型和等位基因分布在健康对照组、CHB 和 CHB-HCC 组之间相似。未发现基因型、等位基因或单体型分析与 CHB-HCC 风险增加相关。生存分析显示，CHB-HCC 患者的基因型或等位基因与 OS 无关。
我们无法证明 PNPLA3 rs738409、TM6SF2 rs58542926 和 HSD17B13 rs72613567 与 CHB-HCC 的发展或预后相关，支持了最初的假设，即它们应被视为具有肝脂肪变性特征的肝病的特定热点。
