Cyclin D1 G870A polymorphism: Association with uterine leiomyoma risk and in silico analysis

Abstract

Uterine leiomyoma (UL) is the most common benign tumor causing considerable morbidity during the reproductive years in women. Cyclin D1 (CCND1) is a cell cycle regulatory protein that is required for the G1 phase, and increased expression levels of this protein may affect tumorigenesis. The present study aimed to assess the possible effect of the CCND1 G870A polymorphism on UL susceptibility. A total of 154 women with UL and 197 healthy women who were age-, body mass index (BMI)- and ethnicity-matched were genotyped for the CCND1 G870A (rs9344) polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. The effects of G870A transition on the structure of mRNA and proteins of CCND1 was evaluated using bioinformatics tools. The frequency of the CCND1 870AA genotype was significantly higher in women with UL compared with the control subjects, and the risk of UL was 1.4-fold higher in women with the AA genotype when compared with the GG genotype before and after adjusting for age, BMI, and ethnicity [odds ratio (OR), 1.4; 95% confidence interval (CI), 1.1-2 (P=0.02)]. The frequency of CCND1 870GA genotype was not significantly different between the two groups. The frequency of the CCND1 870A allele was significantly higher in the women with UL when compared with the control subjects (57 vs. 48%; P=0.02). The in silico analysis revealed that the G870A transition may fundamentally alter the structure of the CCND1-mRNA. Thus, the CCND1 870AA genotype was associated with UL susceptibility in a sample of women from the southeast of Iran.

Keywords: cyclin D1; gene; in silico; polymorphism; uterine leiomyoma.

Figure 1.

G870A transition effects on CCND1-mRNA were analyzed by RNAsnp. (A) Local region with maximum differences in wild-type and mutant CCND1-mRNA. Base pair probabilities of the local region (523–888) detected with the maximum differences depicted. The upper and lower triangle of the matrix represents the base pair probabilities of wild-type and mutant sequences, respectively. The mutated nucleotide is presented by the arrow. (B) The optimal secondary structure of global wild-type sequence (523–888; circled) with a minimum free energy of −138.70 kcal/mol. (C) The optimal secondary structure of global mutant sequence (523–888; circled) with a minimum free energy of −134.50 kcal/mol.