Identificação de potenciais biomarcadores no hipotireoidismo gestacional através do transcriptoma de RNAs circulantes e sua associação com complicações hipertensivas

Abstract

Gestational hypothyroidism has a prevalence that varies in each country because it depends on the distribution of iodine and ethnic factors, being approximately 3% in Latin America. In iodine-deficient countries, this is the main cause of the onset of hypothyroidism during gestation, and in sufficient iodine countries, Hashimoto's thyroiditis is the leading cause. During gestation, there is an increased need for iodine due to increased renal iodide loss because of the increased glomerular filtration rate and decreased renal tubular absorption occurring during gestation. Gestational hypothyroidism leads to several maternal and negative fetal outcomes such as gestational hypertension, anemia, postpartum hemorrhage and pre-eclampsia for the mother and low birth weight and reduced intellectual function of the offspring. Pre-eclampsia has a similar prevalence of 5% to 8% being one of the major causes of perinatal and maternal death worldwide. The use of circulating RNA has been used as a biomarker of some diseases because it is a non-invasive diagnostic or prognostic mode. Pregnant women are a target audience for the use of circulating RNA. Therefore, since gestational hypothyroidism may lead to pre-eclampsia, the objective of this study was to identify differentially expressed genes in healthy pregnant women, pregnant women with hypothyroidism, and pre-eclamptic pregnant women. We used differential gene expression lists of pregnant women with hypothyroidism to identify genes related to hypertensive diseases where we found 61 in common. We did a quantitative analysis of the lists of generated libraries and found 96 common genes among our patient groups and validated these libraries with international transcriptomes. Studying the 96 common genes, we observed that a group of genes, which encode olfactory receptor proteins, was prevalent. Some olfactory receptor genes have already been demonstrated in the literature as a blood pressure regulator and expressed in the kidney. We chose two olfactory receptor genes for validation. We identified that olfactory receptor genes correlate (r: 0.965 and p <0.01) and are associated with hypertension (p = 0.018 and p = 0.022).