Variants and Haplotypes of SIRT1 (rs7895833, rs7069102, and rs2273773) are Associated with the Risk of Preeclampsia and Affect the Trace Elements and Antioxidant Enzymes Levels.

ABSTRACT

Preeclampsia is the most common and serious complication of pregnancy. Variants of Sirtuin-1 (SIRT1) as a key player in the regulation of oxidant/antioxidant signaling pathways might be involved in the pathogenesis of preeclampsia. In the present case-control study 300 women with and without preeclampsia were studied for SIRT1 variants (rs7895833, rs7069102, and rs2273773) and haplotypes. Also, the relationship of glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities and Zn, Cu, and Se levels to the polymorphisms were investigated. The SIRT1 rs7895833 A > G, rs7069102 C > G, and the rs2273773 C > T polymorphisms were associated with the risk of preeclampsia. We found the haplotypes G (rs7895833) C (rs7069102) C (rs2273773), GCC, and ACC compared to the AGT decreased the risk of preeclampsia. The risk haplotype of AGT was associated with higher GPx activity compared to the GCC haplotype. A significantly higher level of Cu and lower levels of Zn and Se in patients with preeclampsia compared to controls were detected. Also, a significantly lower SOD and higher GPx activity in preeclamptic patients compared to controls were found. The three risk genotypes of AA (rs7895833), GG (rs7069102), and TT (rs2273773) significantly decreased the Zn level and SOD activity, and the TT genotype (rs2273773) increased the Cu level in all studied women. The presence of rs7069102 polymorphism was associated with enhanced systolic blood pressure. For the first time, we indicated three SIRT1 polymorphisms and the AGT haplotype are risk factors for preeclampsia development. Also, SIRT1 variants and haplotypes affect the levels of antioxidant enzymes and their cofactors, complicating the pregnancy outcome.