Analysis of the Association of Preeclampsia with Polymorphisms of the <i>INS</i>, <i>INSR </i>and <i>IRS1 </i>Genes in Mexican Women

Abstract

Background/Aims: It has been proposed that preeclampsia is a metabolic syndrome of pregnancy. The polymorphisms PstI and MaeIII of INS, NsiI of INSR and Ala513Pro and Gly972Arg of IRS1 have been associated with metabolic syndrome; moreover, the products of these genes are functionally contiguous during insulin signaling. The aim of this study was to assess whether these polymorphisms are associated with preeclampsia. Methods: 46 normotensive pregnant women and 43 preeclamptic patients were included in the study to develop a clinical, biochemical and genotypic profile of preeclampsia. Clinical evaluation consisted of measurement of blood pressure, height and weight. Peripheral blood samples were collected for determination of fasting glucose and insulin concentrations and for extraction of genomic DNA. Proteinuria was determined. Polymorphisms were detected using PCR-RFLP. Results: The normotensive and preeclampsia groups did not differ significantly in clinical and biochemical traits, except for systolic and diastolic blood pressure (p < 0.0001). Polymorphisms previously associated with metabolic syndrome in Mexican populations were not associated with preeclampsia in Mexican women (p > 0.05). Conclusion: The lack of an association between preeclampsia and the polymorphisms studied suggests that other genes whose products do not have direct functional interaction with metabolic syndrome or epigenetic factors may play a role in preeclampsia.

Genetic Variants in Preeclampsia: Lessons From Studies in Latin-American Populations

“…Hyperinsulinemia is harmful and resembles the endothelial dysfunction observed in PE pathophysiology (Muniyappa and Sowers, 2014). An interesting Mexican study evaluating the role of genetic variants of genes involved in insulin responsiveness in PE development focused on: insulin [( INS ); Pst I (rs3842752) and Mae III (rs689)], insulin receptor [( INSR ); Nsi I (rs2059806)], and insulin receptor substrate [( IRS1 ); Ala513Pro (rs1801276) and Gly972Arg (rs1801278)] (Machorro-Lazo et al, 2009). Although no statistical difference in SNPs frequencies was observed, a previous study evaluating different ethnic groups in Mexico observed differences in the Mae II, Pst I, and Nsi I genotype distribution when stratified by fasting insulin and serum triglyceride levels (Flores-Martínez et al, 2004; Sánchez-Corona et al, 2004).…”

The INSR rs2059806 single nucleotide polymorphism, a genetic risk factor for vascular and metabolic disease, associates with pre-eclampsia

“…A previous study of Mexican women, demonstrated that the INSR rs2059806 SNP was not associated with pre-eclampsia (Machorro-Lazo et al, 2009). The association of the SNP with pre-eclampsia in Caucasian women, the association of the SNP with pre-eclampsia only in the presence of SGA in Sinhalese women and the lack of association among Mexican women highlights the importance of the confounding effect of ethnicity on the possible role of genetic variation in multifactorial diseases.…”