title: CCND2 polymorphisms associated with clearance of HBV infection.
abstract: 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, Pcorr=0.001 and odds ratio=1.37, P=0.0009, Pcorr=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-ht1 was 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.
authors.affiliation: Department of Life Science, Sogang University, Shinsu-dong, Mapo-gu, Seoul, Korea.
authors.forename: Tae Joon
authors.initials: TJ
authors.lastname: Park
authors.forename: Ji-Yong
authors.initials: JY
authors.lastname: Chun
authors.forename: Joon Seol
authors.initials: JS
authors.lastname: Bae
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Hyo Suk
authors.initials: HS
authors.lastname: Lee
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D002874:Chromosome Mapping; D056742:Cyclin D2 / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006509:Hepatitis B / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models; D056910:Republic of Korea / Q000453:epidemiology
chemical_list: C080336:CCND2 protein, human; D056742:Cyclin D2