CCND2 polymorphisms associated with clearance of HBV Infection

초록

Cyclin D2s (CCND2s) are members of the D-type cyclin family. They interact and construct complexes with cyclin-dependent kinase (CDK) 4 or 6. The cyclin D2/CDK4 or CDK6 complexes have key roles in controlling the progression of cell cycle from the Gap 1 (G1) phase to the synthesis (S) phase. Overexpression of cyclin D2 is associated with the development of tumors. In this study, we identified 16 sequence variants of CCND2 polymorphisms through direct DNA sequencing in 24 individuals, and 5 common variants were selected for genotyping in larger-scale subjects (n=1100). Genetic associations of those polymorphisms with hepatitis B virus (HBV) clearance and hepatocellular carcinoma (HCC) outcome among patients with HBV were analyzed. Although no significant association was observed between the polymorphisms and HCC outcome among HBV patients, one common polymorphism in the 5'-untranslated region (that is, rs1049606) and the most common haplotype (CCND-ht1 [T-C-T-A-T]), however, were significantly associated with HBV clearance (odds ratio=0.69, P=0.0002, P(corr)=0.001 and odds ratio=1.37, P=0.0009, P(corr)=0.004, respectively). The minor allele frequency of rs1049606 among the spontaneously recovered (SR) group was significantly higher than that of the chronic carrier (CC) group (frequency=0.403 vs 0.336, P=0.0002). In contrast, the frequency of CCND-ht1was higher among the CC group than among the SR group (frequency=0.429 vs 0.374, P=0.0009). The information identified in this study might provide valuable insights into generating strategies for control of HBV. Journal of Human Genetics (2010) 55, 416-420; doi:10.1038/jhg.2010.36; published online 23 April 2010

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