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Published on: July 28, 2016
Functional MPO Polymorphisms and Haplotypes Affect Both Myeloperoxidase Levels and Association with Hypertensive
Daniela Alves Pereira1, Marcelo Rizzatti Luizon1,2, Ricardo Carvalho Cavalli3
1Department of Physiology and Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista (UNESP), Distrito Rubiao Junior, Botucatu 18680-000, SP, Brazil.
Abstract:
Preeclampsia (PE) shares common pathophysiological mechanisms with cardiovascular diseases, including endothelial dysfunction and exacerbated inflammatory response. Myeloperoxidase (MPO) has been suggested as a biomarker for cardiovascular risk, and its circulating levels are contradictory in PE. Elevated levels of MPO can promote host tissue damage and trigger vascular injury. MPO gene polymorphisms affect circulating MPO levels under different conditions. To date, no studies have investigated whether MPO polymorphisms influence MPO levels in hypertensive disorders of pregnancy. In this study, we examined the impact of two specific MPO polymorphisms-rs2243828 and rs2071409-and their associated haplotypes on MPO levels. We also explored their potential association with gestational hypertension (GH) and preeclampsia (PE). Our study included 136 healthy pregnant women (HP), including 118 with GH and 140 with PE. Genotyping was performed using TaqMan allele discrimination assays, and MPO levels were quantified using an ELISA assay. The TT genotype of the rs2243828 polymorphism was associated with lower MPO concentration in GH, and the CC genotype presented a higher frequency in the GH group than the HP group. The AC+CC rs2071409 polymorphism was associated with lower MPO concentration in GH. We also found that the 'C, C' haplotype was less frequent and was associated with lower MPO concentration in PE. Our findings suggest that both rs2243828 and rs2071409 polymorphisms might contribute to MPO levels in GH and that the haplotype 'C, C' formed by them may protect against PE.
Insights
Investigating myeloperoxidase (MPO) gene variations in pregnancy, this study found specific MPO polymorphisms linked to lower MPO levels in gestational hypertension and potentially protective effects against preeclampsia.
Area of Science:
- Obstetrics and Gynecology
- Cardiovascular Disease Research
- Human Genetics
Background:
- Preeclampsia shares mechanisms with cardiovascular diseases, involving endothelial dysfunction and inflammation.
- Myeloperoxidase (MPO) is a cardiovascular risk biomarker with conflicting levels in preeclampsia.
- MPO gene polymorphisms are known to influence MPO levels, but their role in hypertensive pregnancy disorders is unexplored.
Purpose of the Study:
- To investigate the impact of MPO polymorphisms (rs2243828 and rs2071409) and their haplotypes on MPO levels.
- To explore the association between these MPO polymorphisms and gestational hypertension (GH) and preeclampsia (PE).
Main Methods:
- Genotyping of 136 healthy pregnant women (HP), 118 with GH, and 140 with PE using TaqMan allele discrimination assays.
- Quantification of MPO levels via ELISA assay.
- Analysis of specific MPO polymorphisms (rs2243828, rs2071409) and their haplotypes.
Main Results:
- The TT genotype of rs2243828 was linked to lower MPO concentration in GH.
- The CC genotype of rs2243828 was more frequent in the GH group compared to the HP group.
- The AC+CC genotypes of rs2071409 were associated with lower MPO concentration in GH.
- The 'C, C' haplotype was less frequent and associated with lower MPO concentration in PE.
Conclusions:
- MPO polymorphisms rs2243828 and rs2071409 may influence MPO levels in gestational hypertension.
- The 'C, C' MPO haplotype might offer a protective effect against preeclampsia.
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