ADIPOQ polymorphisms and haplotypes affect circulating adiponectin levels and their association with gestational hypertension and preeclampsia

ADIPOQ多态性和单倍型影响循环脂联素水平及其与妊娠期高血压和子痫前期的关系

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Abstract

INTRODUCTION: Imbalance of adipocytokines has been implicated in endothelial dysfunction in hypertensive disorders of pregnancy (HDP). Adiponectin is an adipocytokine that regulates metabolism, insulin sensitivity, and inflammation, and increased adiponectin levels have been associated with mortality in subjects with cardiovascular diseases. Adiponectin also plays a role in trophoblast invasion during placental development. ADIPOQ gene has polymorphisms that modulate adiponectin levels and are linked to several diseases, including gestational hypertension (GH) and preeclampsia (PE). However, no previous study has examined whether ADIPOQ SNPs and haplotypes affect adiponectin levels in HDP. OBJECTIVES: We assessed and compared plasma adiponectin levels among healthy pregnant (HP, n = 182), GH (n = 121), and PE (n = 133) women, and examined whether ADIPOQ SNPs rs266729, rs2241766 and rs1501299, and their haplotypes are associated with susceptibility to HDP; and whether these polymorphisms and haplotypes affect adiponectin levels in HP, GH and PE. MATERIALS AND METHODS: Adiponectin concentrations were determined using the Human Adiponectin ELISA kit. Genotypes were determined by Taqman allele discrimination assays. Haplotype frequencies were estimated using Haplo. stats. Multiple logistic/linear regression analyses were adjusted for selected covariates. RESULTS: Plasma adiponectin levels were higher in PE than in HP, including when patients were stratified by body mass index. Regarding rs266729 (C>G) SNP, the GG genotype was associated with risk for GH, and the CG genotype may protect against PE. PE patients carrying the CG and GG genotypes showed higher adiponectin levels than their CC counterparts. The 'G,T,G' haplotype showed higher adiponectin levels in PE than in HP, and the 'C,T,T' haplotype may protect against GH. CONCLUSION: Our novel findings indicate that ADIPOQ polymorphisms and haplotypes may affect circulating adiponectin levels and the susceptibility to GH and PE.

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