The p53-HDM2 gene-gene polymorphism interaction is associated with the development of missed abortion.

BACKGROUND

The interaction between p53 and human double minute 2 (HDM2) plays an important role in apoptosis; therefore, functional polymorphisms in these genes might have adverse effects in early pregnancy. In this study, we investigated whether p53 codon 72 and HDM2 promoter (SNP309) polymorphisms were associated with the development of missed abortion.

METHODS

Women with missed abortions (n= 60) and healthy controls (n= 64) were included in the study. Genotyping of the p53 codon 72 and HDM2 SNP309 (T > G) polymorphisms was performed by PCR with sequence-specific primers and PCR-restriction fragment length polymorphism analysis, respectively, using villous samples. The mRNA and protein levels for p53 and HDM2 were measured by real-time PCR and semi-quantitative immunohistochemistry, respectively.

RESULTS

For the p53 codon 72 polymorphism, no difference in genotype or allele frequencies was observed in women with missed abortion versus controls. However, for the HDM2 SNP309 (T > G) polymorphism, G/G genotype was associated with a higher risk of missed abortion compared with the T/T+ T/G genotypes (P= 0.043). Women carrying the HDM2 G/G genotype or p53 Pro/Pro genotype had higher HDM2 mRNA (P= 0.04 and P= 0.013, respectively) and protein (P= 0.001 and P= 0.037, respectively) levels than women with other HDM2 SNP309 and p53 codon 72 genotypes.

CONCLUSIONS

The genotypes HDM2 SNP309 G/G and p53 codon 72 Pro/Pro can induce high levels of HDM2, which may be associated with missed abortion.