Relationships between the <i>Osteocalcin</i> Gene Polymorphisms, Serum Osteocalcin Levels, and Hepatitis B Virus-Related Hepatocellular Carcinoma in a Chinese Population

Abstract

<div><p>Background</p><p>Available evidence has demonstrated that osteocalcin may play a role in pathogenesis of cancer, and mutation of the <i>osteocalcin</i> gene may be involved in the cancer development. The aim of this study is to determine whether <i>osteocalcin</i> gene polymorphisms are associated with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) among Chinese population.</p><p>Methods</p><p>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 <i>osteocalcin</i> gene <i>rs1800247</i> and <i>rs1543297</i> polymorphisms.</p><p>Results</p><p>Compared with healthy controls, the <i>rs1800247</i> 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, <i>P</i> <0.001; Hh versus hh: OR = 6.306, 95% CI 3.480–11.423, <i>P</i> <0.001, respectively). Similarly, the subjects bearing the H allele of <i>rs1800247</i> had more than a 2.4-fold increased risk for development of HCC (OR = 2.484, 95% CI 1.747–3.532, <i>P</i> <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 (<i>P</i> = 0.003) and CT genotype (<i>P</i> <0.001). In contrast, there were no significant differences in the genotype and allele of <i>rs1543297</i> polymorphisms between the groups of patients and healthy controls.</p><p>Conclusions</p><p>These findings for the first time suggest that genetic variant in <i>osteocalcin</i> gene <i>rs1800247</i> polymorphisms may be a risk factor for HBV-related HCC. We also find an inverse association of serum osteocalcin levels with HCC.</p></div