Preeclampsia (preeclampsia) - Genes CORIN, EPHX1 and STOX1
Preeclampsia is a complication of pregnancy in which the affected woman develops hypertension, which may be accompanied by excessive proteinuria. This disorder usually occurs in late pregnancy and often requires premature birth. In many women with mild preeclampsia the problem is first detected through blood pressure and urinalysis. Other baseline characteristics of the disease are facial or hand edema and weight gain of more than 1 kg in a few days. In the most intense forms, affected women may experience headaches, dizziness, irritability, oliguria, upper abdominal pain, nausea or vomiting. Sometimes there may be changes in vision, including photophobia, blurred vision or temporary blindness.
In most cases, preeclampsia is mild and goes away within a few weeks after delivery. However, in severe cases, the disease can affect organs such as the heart, liver and kidneys and can trigger life - threatening complications. Extreme hypertension in the mother can lead to a hemorrhagic stroke. Hypertensive encephalopathy may also lead to seizures. If you suffer from seizures, the condition is considered to have progressed to eclampsia, which can lead to coma. Between 10 and 20 percent of women with severe preeclampsia develop another potentially fatal complication called HELLP syndrome. This syndrome causes hemolysis and elevated liver enzymes and low platelets. Severe preeclampsia can also affect the fetus, causing deterioration of the flow of blood and oxygen, which causes growth problems or stillbirth. Newborns born prematurely because the disease can have complications associated with prematurity, such as respiratory problems due to underdeveloped lungs. Women who have had preeclampsia have approximately twice the risk, compared to the general population of women suffer throughout their lives ao heart disease and / or stroke.
The specific causes of preeclampsia are not well understood. In some women the body does not react correctly to changes in fluid during pregnancy, leading to problems with high blood pressure and urine production in the kidneys that occur in preeclampsia. The reasons for these abnormal reactions to changes of pregnancy vary in different women and may differ depending on the stage of gestation at which the disease develops. Studies suggest that preeclampsia is related to a problem with the placenta. If there is an insufficient connection between the placenta and arteries of the uterus, placenta does not get enough blood. In response , the organism responds by releasing various substances, including molecules that affect the vascular endothelium. By mechanisms that are unclear, the reaction of the vascular endothelium appears to increase the factors that cause the blood vessels to constrict. As a result, the blood vessels constrict abnormally, resulting in hypertension. These abnormalities of blood vessels also affect the kidneys, causing some proteins that are normally absorbed into the blood is excreted in the urine.
It is believed that variations in genes involved in fluid balance, the operation of vascular endothelium, or placental development affect the risk of developing preeclampsia. Many other factors probably also contribute to the risk of developing this complex disorder. These risk factors include a first pregnancy, a twin or multiple pregnancy, obesity, be greater than 35 or less than 20 years, history of diabetes, hypertension or renal disease and preeclampsia in a previous pregnancy. Socioeconomic status and ethnicity have also been associated with increased risk. The incidence of the disease in the United States has increased 30 percent in recent years, partly attributed to an increase in older mothers and multiple births resulting from the use of assisted reproduction methods.
Sometimes the disease is a result of mutations in CORIN (corin, peptidase serine), EPHX1 (epoxide hydrolase 1) and STOX1 (storkhead box 1) genes.
Corin gene, located on the short arm of chromosome 4 (4p12), encodes a member of the serine protease type II transmembrane superfamily trypsin. Members of this family are composed of multiple structurally distinct domains. The encoded protein becomes natriuretic peptide pro-atrial natriuretic peptide in the biologically active headset, a cardiac hormone that regulates blood volume and blood pressure. This protein may also function as a type natriuretic peptide proconvertase.
The EPHX1 gene, located on the long arm of chromosome 1 (1q42.1), encoding the epoxide hydrolase enzyme, which plays a role in both the activation and detoxification of epoxides. Mutations in this gene cause a deficiency of epoxide hydrolase enzyme or an increased activity.
The STOX1 gene, located on the long arm of chromosome 10 (10q22.1), encodes a protein that can act as a DNA binding protein. It is involved in the regulation of oxidative reactive species concentrations and reactive nitrogen species, roasted and mitochondrial homeostasis in the placenta. Mutations in this gene cause loss of function.
Most cases of preeclampsia does not appear to be inherited. The tendency to develop the disorder seems to run in families. However, the pattern of inheritance is unknown.
Tests in IVAMI: in IVAMI perform detection of mutations associated with preeclampsia, by complete PCR amplification of the exons of CORIN, EPHX1 and STOX1 genes, respectively, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).