Liu Yanqiong, Huang Liying, Lu Yu, Xi Xue-E, Huang Xiu-Li, Lu Qinghua, Huang Xiamei, Li Shan, Qin Xue
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Department of Clinical Laboratory, Nanning Social Welfare Hospital, Nanning, Guangxi, China.
PLoS One. 2015 Jan 14;10(1):e0116479. doi: 10.1371/journal.pone.0116479. eCollection 2015.
Available evidence has demonstrated that osteocalcin may play a role in pathogenesis of cancer, and mutation of the osteocalcin gene may be involved in the cancer development. The aim of this study is to determine whether osteocalcin gene polymorphisms are associated with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) among Chinese population.
A total of 515 subjects were divided into four groups: 129 patients with chronic hepatitis B (CHB), 62 patients with HBV-related liver cirrhosis (LC), 154 patients with HBV-related HCC, and 170 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect osteocalcin gene rs1800247 and rs1543297 polymorphisms.
Compared with healthy controls, the rs1800247 HH and Hh genotypes were associated with a significantly increased susceptibility to HCC (HH versus hh: OR = 6.828, 95% CI 2.620-17.795, P < 0.001; Hh versus hh: OR = 6.306, 95% CI 3.480-11.423, P < 0.001, respectively). Similarly, the subjects bearing the H allele of rs1800247 had more than a 2.4-fold increased risk for development of HCC (OR = 2.484, 95% CI 1.747-3.532, P < 0.001) compared with those bearing the h allele. In addition, we found significant decreased serum osteocalcin levels in HBV-related HCC patients (11.73 ± 8.18 ng/mL) compared with healthy controls (15.3 ± 6.06 ng/mL). Furthermore, the serum osteocalcin levels were significantly lower in HCC patients than healthy controls among the individuals with heterozygous Hh genotype (P = 0.003) and CT genotype (P < 0.001). In contrast, there were no significant differences in the genotype and allele of rs1543297 polymorphisms between the groups of patients and healthy controls.
These findings for the first time suggest that genetic variant in osteocalcin gene rs1800247 polymorphisms may be a risk factor for HBV-related HCC. We also find an inverse association of serum osteocalcin levels with HCC.
现有证据表明骨钙素可能在癌症发病机制中起作用，且骨钙素基因突变可能参与癌症发展。本研究旨在确定中国人群中骨钙素基因多态性是否与乙型肝炎病毒（HBV）相关肝细胞癌（HCC）有关。
共515名受试者分为四组：129例慢性乙型肝炎（CHB）患者、62例HBV相关肝硬化（LC）患者、154例HBV相关HCC患者和170名健康对照。采用聚合酶链反应-限制性片段长度多态性策略检测骨钙素基因rs1800247和rs1543297多态性。
与健康对照相比，rs1800247的HH和Hh基因型与HCC易感性显著增加相关（HH与hh相比：OR = 6.828，95%CI 2.620 - 17.795，P < 0.001；Hh与hh相比：OR = 6.306，95%CI 3.480 - 11.423，P < 0.001）。同样，携带rs1800247的H等位基因的受试者发生HCC的风险比携带h等位基因的受试者增加2.4倍以上（OR = 2.484，95%CI 1.747 - 3.532，P < 0.001）。此外，我们发现HBV相关HCC患者的血清骨钙素水平（11.73±8.18 ng/mL）与健康对照（15.3±6.06 ng/mL）相比显著降低。此外，在杂合子Hh基因型（P = 0.003）和CT基因型（P < 0.001）的个体中，HCC患者的血清骨钙素水平显著低于健康对照。相比之下，患者组和健康对照组之间rs1543297多态性的基因型和等位基因无显著差异。
这些发现首次表明骨钙素基因rs1800247多态性中的基因变异可能是HBV相关HCC的一个危险因素。我们还发现血清骨钙素水平与HCC呈负相关。
