Apolipoprotein E (Apo E) gene polymorphisms and recurrent pregnancy loss: a meta-analysis

Abstract

Background Recently, a relationship between recurrent pregnancy loss (RPL) and Apolipoprotein E (Apo E) gene polymorphisms has been proposed. In order to investigate the real association between Apo E polymorphisms and RPL, our meta-analysis was carried out. Methods We estimated the association with RPL risk under dominant and recessive models, in combination with the OR and RR with a 95 % confidence interval (CI), which was used to assess the association between RPL and Apo E polymorphisms. Results According to our criterion, there were 6 studies included. The dominant model used the E4/E3 group and the OR was 1.919 (95 %CI: 1.016-3.625, I 2 =53.8 %), the RR was 1.308 (95 %Cl: 1.071-1.598) suggesting that carriers of the E4 allele would have a higher risk of causing spontaneous miscarriages. In addition, the OR was 0.727 (95 %CI: 0.566-0.932, I 2 =0.0 %) and RR was 0.923 (95 %CI: 0.867-0.982) in a fixed model for E3/E3 homozygotes versus other genotypes, suggesting that the Apo E3 polymorphism could be a protective factor. The OR was 1.365 (95 % CI: 1.029-1.811, I 2 =0 .0 %) in a fixed model comparing the E2 allele with the E3 allele, suggesting that Apo E2 polymorphisms may contribute to RPL as a risk factor. Furthermore, after conducting sensitivity analysis in the E4/E3 group, the results showed this to be consistent and the OR was 2.249 (95 %CI: 1.474-3.431). Conclusions There is a close association between RPL and Apo E gene polymorphisms. For RPL, the Apo E4 polymorphism could be a risk factor, the Apo E3 polymorphism may be a protective factor and the Apo E2 polymorphism may be another potential risk factor.

Child apolipoprotein E gene variants and risk of cerebral palsy: Estimation from case–parent triads

“…This would be consistent with the observations that APOEε2 and APOEε4 are related to poor repair processes in the brain after insults in adults. 3e7 This interpretation is also supported by a finding in a recent study by Li et al (2014) who found an association between recurrent pregnancy loss and the APOEε2 and APOEε4 alleles in the mother, whereas the APOEε3 polymorphism was interpreted by Li to be a protective factor. 21 Molecular mechanisms explaining a possible increased risk for death after fetal brain injury when APOEε4 is present, may be impaired repair processes following an adverse event in utero, in particular through reduced ability to modulate the inflammatory response.…”

“…3e7 This interpretation is also supported by a finding in a recent study by Li et al (2014) who found an association between recurrent pregnancy loss and the APOEε2 and APOEε4 alleles in the mother, whereas the APOEε3 polymorphism was interpreted by Li to be a protective factor. 21 Molecular mechanisms explaining a possible increased risk for death after fetal brain injury when APOEε4 is present, may be impaired repair processes following an adverse event in utero, in particular through reduced ability to modulate the inflammatory response. Zhang et al, in 2010 pointed to immunoregulatory dysfunction in APOEε4 carriers, and Gale et al (2014) also found that APOEε4 allele carriers differed in their immune responses compared to non-carriers.…”

Genetic association between FXIII and β-fibrinogen genes and women with recurrent spontaneous abortion: a meta- analysis

“…However, in our analysis, our results showed that the β-fibrinogen -455G/A polymorphism was not associated with RSA. These results suggested that the β-fibrinogen -455G/A polymorphism was not a risk factor for fetal loss, which was supported by Pihusch et al [32] and Poursadegh Zonouzi et al [33]. With the different outcomes, patient selections have been considered one possible reason.…”

“…Although serious damage is presented, the accurate pathogenesis of RSA remains unknown in~50 % of cases [1,33]. There is a strong belief that RSA patients with unknown etiology have a multifactorial condition and that genetic and environmental elements play a key role.…”

“…There is a strong belief that RSA patients with unknown etiology have a multifactorial condition and that genetic and environmental elements play a key role. Several meta-analyses have been published focusing on thrombophilic gene mutations and their association with RSA such as apolipoprotein E and the angiotensin converting enzyme gene [33,34]. However, there is no meta-analysis of the prevalence of FXIII Val34Leu or β-fibrinogen -455G/A polymorphisms in patients with a history of RSA.…”