Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, PR China.
Department of Laboratory Medicine, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.
Clin Res Hepatol Gastroenterol. 2016 Nov;40(5):614-621. doi: 10.1016/j.clinre.2015.12.015. Epub 2016 Feb 5.
Mannose-binding lectin (MBL) is a member of the calcium-dependent collectin family involved in the innate immune system that mediates phagocytosis and activates complement by binding to carbohydrate motifs. We studied allele and haplotype frequencies of -221C/G and codon 54G/A in MBL2 gene to reveal their relationship with the developing and progression of hepatitis B virus (HBV)-related liver diseases.
This study was performed in 171 healthy controls, 133 chronic hepatitis B (CHB) patients, 97 patients with HBV-related liver cirrhosis (LC) and 334 HBV-related hepatocellular carcinoma (HCC) patients. The genotypes of these two polymorphisms in these subjects were detected using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. Stratification analyses by clinical characteristics and survival analysis of HCC patients were also performed according to their genotypes.
The genotype and allele frequencies at codon 54 manifested a significant difference between healthy controls and patients with progressive HBV-related liver diseases, especially liver cirrhosis. Allele A appeared to have protective effect from developing LC and HCC compared with G allele. The percentages of the patients with G allele at -221C/G increased in HBV-related disease groups. When combined together as a haplotype, lower haplotype AC frequency was associated with a decreased risk for the progression of HBV-related liver diseases and HCC developing. Furthermore, HCC patients with G allele at codon 54 showed to have better survival than those with A allele.
These results indicated that polymorphisms in MBL2 gene may influence susceptibility, progression and prognosis of HBV-related liver diseases.
甘露糖结合凝集素(MBL)是钙依赖性凝集素家族的成员,参与先天免疫系统,通过与碳水化合物基序结合介导吞噬作用并激活补体。我们研究了 MBL2 基因-221C/G 和密码子 54G/A 的等位基因和单倍型频率,以揭示它们与乙型肝炎病毒(HBV)相关肝病的发生和发展的关系。
本研究纳入了 171 名健康对照者、133 名慢性乙型肝炎(CHB)患者、97 名乙型肝炎相关肝硬化(LC)患者和 334 名乙型肝炎相关肝细胞癌(HCC)患者。采用聚合酶链反应-连接酶检测反应(PCR-LDR)法检测这些受试者中这两种多态性的基因型。根据基因型对这些患者进行临床特征分层分析和 HCC 患者生存分析。
密码子 54 的基因型和等位基因频率在健康对照者和进展性 HBV 相关肝病患者之间存在显著差异,尤其是肝硬化患者。与 G 等位基因相比,A 等位基因似乎对发展 LC 和 HCC 具有保护作用。-221C/G 的 G 等位基因患者的百分比在 HBV 相关疾病组中增加。当组合在一起作为单倍型时,较低的 AC 单倍型频率与降低 HBV 相关肝病和 HCC 发展的风险相关。此外,密码子 54 为 G 等位基因的 HCC 患者的生存情况好于 A 等位基因的患者。
这些结果表明 MBL2 基因多态性可能影响 HBV 相关肝病的易感性、进展和预后。