Key result
Although individual ERAP1 and ERAP2 single nucleotide polymorphisms were not associated with preeclampsia, the ACGACGT haplotype significantly increased the risk of the disorder (OR 3.657).
Why the study?
ERAP1 and 2 regulate blood pressure and their SNPs have been linked to preeclampsia, but their association in Iranian preeclamptic women required assessment.
Are ERAP1 and ERAP2 gene polymorphisms and haplotypes associated with the risk of preeclampsia in Iranian women?
Case-Control (n=281)
No
Are ERAP1 and ERAP2 gene polymorphisms and haplotypes associated with the risk of preeclampsia in Iranian women?
Odds Ratio: 3.657 (95% CI 1.63–8.206)
Absolute Event Rate: 10% vs 3%
p-value: p=0.00082
While individual ERAP1 and ERAP2 SNPs were not significantly associated with preeclampsia in Iranian women, specific haplotypes significantly altered the risk, highlighting the importance of polygenic interactions in the disease's pathogenesis.
Haplotype analysis may flag preeclampsia susceptibility in Iranian women; hypothesis-generating for ERAP polygenic research before any clinical use.
Background: Endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and 2) are involved in blood pressure regulation and single nucleotide polymorphisms (SNPs) of these genes have been linked to preeclampsia. This study intended to assess the association of ERAP1 and 2 genes polymorphism with Iranian preeclamptic women. Methods: In this case-control study, 148 preeclamptic and 133 pregnant women were selected from the Kosar Hospital, Qazvin, Iran, during 2013-2015. In order to genotype the subjects for rs28096, rs30187, rs26653, rs3734016, rs34750 and rs2549782, rs17408150 for ERAP1 and 2 genes, respectively, Real-Time PCR allelic discrimination approach was exploited. Results: Neither allelic nor genotype frequencies of all seven polymorphisms were significantly different between two groups. Though, ACGACTT and GTCAGGA haplotypes were related with decreased (P=0.0079, OR=0.559, 95% CI: 0.363-0.861 and P=0.02, OR=0.417, 95% CI: 0.194-0.896, respectively), but ACGACGT and GTGACTT haplotypes were associated with an increased (P=0.00082, OR=3.657, 95% CI: 1.630-8.206 and P=0.02, OR=2.401, 95% CI: 1.119-5.151, respectively) risk of preeclampsia. Moreover, some positions were detected to be in linkage disequilibrium. Conclusion: Ongoing investigation resulted differently from before performed studies considering the role of ERAP1 and ERAP2 gene polymorphisms in predisposing women to preeclampsia, emphasizing on the genetic structure differences among various racial populations.
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Dargahi et al. (2019) conducted a case-control in Preeclampsia (n=281). ERAP1 and ERAP2 gene polymorphisms and haplotypes vs. Healthy pregnant women (unexposed/reference alleles) was evaluated on Risk of preeclampsia associated with the ACGACGT haplotype of ERAP1 and ERAP2 genes (OR 3.657, 95% CI 1.630-8.206, p=0.00082). Although individual ERAP1 and ERAP2 single nucleotide polymorphisms were not associated with preeclampsia, the ACGACGT haplotype significantly increased the risk of the disorder (OR 3.657).
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