Genetic predisposition to idiopathic recurrent spontaneous abortion: contribution of genetic variations in IGF-2 and H19 imprinted genes.

PROBLEM Recurrent spontaneous abortion (RSA) is a common clinical problem with a complex etiology of genetic and non-genetic causes, which remains to be fully determined. IGF-2 stimulates trophoblast invasion, proliferation and maturation of placenta, while H19 RNA suppresses growth. As genomic imprinting plays a critical role in the development of placenta and embryo, our aim was to evaluate the possible role of variations in IGF-2 and H19 imprinted genes as factors of predisposition for RSA. METHOD OF STUDY A case-control study was conducted to determine the association between IGF-2 and H19 gene polymorphisms and the susceptibility to RSA in 113 couples with RSA and 226 controls. PCR/RFLP were performed to analyze IGF-2 ApaI and H19 HhaI polymorphisms. RESULTS We found a statistically significant difference in the genotype frequency distribution of IGF-2 ApaI polymorphism between males from couples with RSA and healthy males (chi2(2) = 45.12; P < 0.0001). There were no differences in the genotype and allele distribution of H19 polymorphism frequencies, or for the IGF-2 ApaI polymorphism between female groups. CONCLUSION The presence of IGF-2 ApaI polymorphism in partners of RSA women could affect IGF-2 level of expression in placenta and embryo and represent a risk factor for RSA susceptibility.