Preeclampsia as a Serious Hypertensive Condition in Pregnancy - Lab Report Example

? Preeclampsia March 27, Preeclampsia is a serious hypertensive condition in pregnancy. Little is known about the actual cause of the condition, and even less about the genomic sequences related to the disease. This literature review looks at an overview of the existing studies performed since 2005, in order to draw conclusions based on their data. ROCK2, ACE, NOS3, H19, COMT, and STOX1 are all discussed as possibilities, though only H19 showed any serious promise as a causal link. Genes related to preeclampsia are more likely to be those related to cardiovascular function than to fetal growth or uterine health. Further research is indicated. Introduction Preeclampsia is a gestational disease of fairly common occurrence. It has effects of varying severity, and may in its worst forms cause a risk to the survival of both mother and fetus [1]. It is primarily linked to high blood pressure during pregnancy, and the risk of suffering from the condition is greatly increased with chronic hypertension in the mother [2]. However, it may also be linked to genetic factors in the fetus and the mother that affect the growth of the placenta, especially the vascular layout of the placenta [3]. Despite the potential severity of the condition and the amount of research conducted, the ultimate cause of preeclampsia is still unknown [4]. Genetic analysis methods have been used in an attempt to determine what genes and proteins associated with those genes are linked to preeclampsia. Coding these genes could allow a statistical determination of risk as well as a codification of the risk factors [5]. Therefore, this paper will look at the current accepted statistical determinants surrounding preeclampsia and what is currently known regarding the genetic risk factors. Materials and Methods A search was done on Google Scholar for the keywords “preeclampsia” and the alternative spelling “pre-eclampsia” and the phrase “preeclampsia risk”, also with the alternative spelling. Precedence was given to those results that were located in journals with the words “bioinformatics”, “statistics”, or “molecular” in the titles, though this was not completely exclusive. This was done in order to obtain studies in the field of bioinformatics that were related to the gestational disease preeclampsia. An additional search restriction was added to that the articles had to be published after 2005, to ensure that only recent results that are currently considered to be accurate are used. An additional search was done on ScienceDirect and PubMed for relevant articles. However, the parameters above returned no results within the ScienceDirect database and very few on PubMed, so the search was re-done with slightly different terms. The search was designed to restrict only to journals generally in the subject areas of molecular genetics or bioinformatics, but may not have had those keywords in the journal name. The same set of keywords was used, with the additional keywords of “molecular genetics” and “bioinformatics” in separate searches added to the phrases. Relevance was determined if the article had certain key factors in the abstract when first viewed. These included the words “risk factors”, “gene”, “allele”, or other keywords relating to genetic sequencing and its use in determining risk for preeclampsia. Therefore, the article was determined to be relevant if it appeared to be related to statistically quantifying or codifying the genetic risk factors for preeclampsia Results One suggested genetic risk factor for preeclampsia was the rho-associated coiled-coil protein kinase 2, or the ROCK2 gene. The ROCK2 gene is located on chromosome 2p25, which previous research has suggested has a link to preeclampsia. However, the gene itself appears to be unrelated to preeclampsia, as when a group of patients were sequenced, there was no correlation between those who had preeclampsia, those who did not suffer from the condition, and the presence or absence of the gene [5]. The gene region pair ACE, angiotensin converting enzyme, and NOS3, nitric oxide synthase 3, are related to blood pressure regulation and inflammation of the joints, so therefore it is unsurprising that they are also related to hypertensive conditions. Preeclampsia is one of these conditions, in addition to unstable angina, brain ischemia, and many others. However, this gene cluster is particularly prone to environmental influences, and so it is only a risk factor for preeclampsia in combination with the right set of outside factors affecting the individual during pregnancy [6]. The H19 gene has also been implicated in preeclampsia, both for its levels of imprinting on the placenta and for the level of DNA methylation of the imprinted gene [4, 7]. One study showed that heterozygous expression of the H19 gene was found in normal pregnancies, but more likely to be linked to preeclampsia. Homozygous expression, however, was only found in those women who then had preeclampsia with their pregnancies, and was linked to more severe forms of hypertension and more severe symptoms of preeclampsia. Additionally, there were some women in the study who had the heterozygote form in their DNA, but then expressed the gene at a level consistent with homozygous expression, which was also correlated to a worse set of symptoms for the condition, including hypertension [7]. A different study linked high levels of DNA (cytosine-5) methyltransferase 1 mRNA with early-onset preeclampsia, indicating that abnormal DNA methylation of that gene area may be linked to the condition[4]. The gene COMT, which codes for the enzyme catechol-O-methyltransferase, has also been connected to the development of preeclampsia. Catechol-O-methyltransferase is involved in the degradation of estrogen and catecholamine, and, as is well-known in the medical field, changes in hormone regulation can have widespread and surprising effects throughout the body. Low levels of expression for the related gene sequence have been linked to preeclampsia, as well as other cardiovascular and hypertensive diseases [8]. The storkhead-box protein 1 is coded for by the gene segment STOX1, is involved in DNA binding, and has been implicated with a link to preeclampsia. This is primarily due to the fact that mutations in the STOX1 gene have been found in women with preeclampsia and those mutations had imprinted to the placenta [9]. However, despite the prominent links between STOX1 and placental growth, later studies have not confirmed that the gene is connected causally with preeclampsia [10, 11]. In fact, what was originally referred to as the mutated form of the gene seems to be the more common form in the population [11]. Discussion From this superficial analysis of the available literature, it is obvious that many studies have been performed to determine the genetic links to preeclampsia. However, none of these studies was able to provide a definitive connection that was present in all cases of preeclampsia, indicating a lack of a direct causation of preeclampsia by a person's genetic code. Some genes have been shown to be more likely in women with preeclampsia, but in the great majority of cases, the gene trigger was not found in even most of the women studied. Conversely, in some cases, the gene was found in its suspected diseased form in the control group as well as the group with preeclampsia. Of all the genes studied in the research reviewed, only H19 showed a definitive difference between expression in the control group and the women who showed preeclampsia symptoms. Indicators lead to the conclusion that what genetic triggers do exist for preeclampsia are likely related to cardiovascular function. Several studies linked women with preeclampsia and the presence of a gene form related to hypertension. This is in opposition to the idea that genes related to preeclampsia would be the ones involved in placental growth or uterine health; those genes seem to have very little to do with the likelihood of developing preeclampsia. Further studies are obviously warranted into the genes connected with preeclampsia. This review has found that such studies should focus on cardiovascular function. While a direct causal link seems unlikely at this juncture, perhaps future studies could locate genes that are likely to be affected by environmental factors and lead to preeclampsia cases. If these connections could be found, future studies could also focus on determining what these environmental factors might be and in what ways they affect those loci, in order to help determine what methods can be used for preeclampsia prevention. Acknowledgements [Use this space to name your relevant professors, your university, and any other affiliations with your research institution] References 1. Redman, C.W. and I.L. Sargent, Latest Advances in Understanding Preeclampsia. Science, 2005. 308(5728): p. 1592-1594. 2. Seed, P.T., et al., Prediction of Preeclampsia and Delivery of Small for Gestational Age Babies Based on a Combination of Clinical Risk Factors in High-Risk Women. Hypertension in Pregnancy, 2011. 30(1): p. 58-73. 3. Redman, C.W., The endoplasmic reticulum stress of placental impoverishment. Am J Pathol, 2008. 173(2): p. 311-4. 4. Gao, W.-l., et al., Detection of global DNA methylation and paternally imprinted H19 gene methylation in preeclamptic placentas. Hypertens Res, 2011. 5. Peterson, H., et al., ROCK2 allelic variants are not associated with pre-eclampsia susceptibility in the Finnish population. Molecular Human Reproduction, 2009. 15(7): p. 443-449. 6. Liu, Y., P. Wise, and A. Butte, The "etiome": identification and clustering of human disease etiological factors. BMC Bioinformatics, 2009. 10(Suppl 2): p. S14. 7. Yu, L., et al., The H19 Gene Imprinting in Normal Pregnancy and Pre-eclampsia. Placenta, 2009. 30(5): p. 443-447. 8. Roten, L.T., et al., A low COMT activity haplotype is associated with recurrent preeclampsia in a Norwegian population cohort (HUNT2). Molecular Human Reproduction, 2011. 9. van Dijk, M. et al. “Maternal segregation of the Dutch preeclampsia locus at 10q22 with a new member of the winged helix gene family.” Nature Genetics 37.5 (2005) : 514-519. 10. Kivinen, K. et al. “Evaluation of STOX1 as a preeclampsia candidate gene in a population-wide sample.” Eur J Hum Genet 15.4 (2007) : 494-497. 11. Berends, A. et al. “Short communication: STOX1 gene in pre-eclampsia and intrauterine growth restriction.” BJOG: An International Journal of Obstetrics & Gynaecology 114.9 (2007) : 1163-1167. Read More