研究动态
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PNPLA3、TM6SF2 和 HSD17B13 的遗传变异对土耳其乙型肝炎患者肝细胞癌的发生或预后有影响吗?

Does Genetic Variation in PNPLA3, TM6SF2 and HSD17B13 have a Role in the Development or Prognosis of Hepatocellular Carcinoma in Turkish Patients with Hepatitis B?

发表日期:2024 Jun 29
作者: Coskun Ozer Demirtas, Fatih Eren, Demet Yilmaz, Osman Cavit Ozdogan, Feyza Gunduz
来源: MEDICINE & SCIENCE IN SPORTS & EXERCISE

摘要:

慢性乙型肝炎 (CHB) 的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,一些患者的病情仍然有所进展。 PNPLA3 rs738409 和 TM6SF2 rs58542926 等单核苷酸多态性 (SNP) 的存在与脂肪肝疾病发展和进展为 HCC 相关,而 HSD17B13 rs72613567:TA 中的剪接变体已被证明具有保护作用。我们研究了这些 SNP 在单纯 CHB 病因学中的 HCC 发展或预后中的作用,在没有肝脂肪变性的情况下,仍然未知。我们在前瞻性招募的队列中分析了 PNPLA3 rs738409、TM6SF2 rs58542926 和 HSD17B13 rs72613567 SNP(n=323) )由健康对照、无肝脂肪变性的 CHB 和 CHB-HCC 患者组成。通过 PCR 分析确定 SNP,并使用调整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、CHB和CHB-HCC组之间相似。没有发现基因型、等位基因或单倍型分析与 CHB-HCC 风险增加相关。生存分析显示没有基因型或等位基因与 CHB-HCC 患者的 OS 相关。我们无法证明 PNPLA3 rs738409、TM6SF2 rs58542926 和 HSD17B13 rs72613567 与 CHB-HCC 的发展或预后有任何关联,支持了最初的假设:它们应被视为以肝脂肪变性为特征的肝脏疾病的特定热点。
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.