Contribution of ADIPOQ Variants to the Genetic Susceptibility of Recurrent Pregnancy Loss
Abstract
Adiponectin is a hormone implicated in regulating energy, lipid, and glucose metabolism and is encoded by the ADIPOQ gene. ADIPOQ variants can regulate the circulating levels of adiponectin. Irregular adiponectin concentrations have been associated with numerous reproductive diseases including recurrent pregnancy loss (RPL). The main objective of this study was to determine whether the 14 selected polymorphisms of the ADIPOQ gene are linked with RPL. The retrospective case-control study comprised a total of 332 women with RPL, adjusted as more than three consecutive abortions of unknown etiology, and 286 healthy controls. They were genotyped for the ADIPOQ variants using allele exclusion method on real-time PCR. Significantly higher rs1501299 minor allele frequencies (MAF) and lower rs2241767 and rs2241766 MAF were seen among RPL women, thereby assigning disease susceptibility and protective aspect to the mentioned variants, respectively. Different associations of ADIPOQ genotypes with RPL were noticed according to the genetic model exploited: rs1501299 and rs2241767 were significantly linked with RPL under the three models, while rs17366568 and rs2241766 were associated with RPL under codominant and dominant models, and rs7649121 was related to RPL under the dominant and recessive models. rs4632532 was linked according to the recessive model only. Based on LD pattern, 2-haplotype blocks were specified. Reduced frequency of AGG and GAGG and increased frequency of TAAG were noted in cases, compared with controls, hence indicating these haplotypes as RPL-protective and RPL-susceptible, respectively. These results support a significant role of ADIPOQ as an RPL candidate locus.