Role of the 820 A/G variant in the IGF-2 gene and recurrent spontaneous abortion in southern Iran: A cross-sectional study

Background: Insulin-like growth factor-2 (IGF-2) is a polypeptide growth factor and one of the first genes expressed prior to the implantation of the embryo, with its highest expression in the placental cells. Its activity strongly depends on the genomic imprinting, and the result of the loss of genetic imprinting is the termination of the early stages of embryonic development, which can lead to recurrent spontaneous abortion.
Objective: This cross-sectional study aimed to investigate the role of 820A/G variant of the IGF-2 gene and the probability to recurrent spontaneous abortion (RSA) in southern Iran.
Materials and Methods: In this study, 50 aborted fetuses tissue for the study group and blood samples umbilical-cord from newborns as control group (n = 50) were collected from Shiraz-Iran (2017). The genotyping of the target point in the IGF-2 gene was performed by Real-time Polymerase Chain Reaction and analyzed through high-resolution melting (HRM) curve.
Results: Based on the collected data (AA genotype = reference), allele “A” frequency in aborted fetus was 51% and control 68% as well as allele G 49% and 32%, respectively. Moreover, 27 aborted embryos (54%) were heterozygous (A/G) (OR = 3.274, 95% CI = 1.015-10.561, p = 0.04), while 18 cases (36%) in control sample showed heterozygosity. Considering the phenotypic status, the G allele had a dominant effect on the incidence of RSA (p = 0.008, OR = 3.167).
Conclusion: Based on the present study, the risk of abortion due to loss of heterozygosity or quantitative decline of the IGF-2 is about three-fold in the southern Iran.

Keywords
Variant; IGF-2; Spontaneous abortion; Genomic imprinting; Gene expression.