The value of using polymorphisms in anti-platelet therapy

OBJECTIVES and BACKGROUNDS： Cardiovascular events occure as a result of various risk factors, such as uric acid （UA）, inflammation, hormones and other materials that induce C- reactive protein （CRP） expression. These factors lead to complement activation, and endothelial damages. Damaged endothelial cells release heparan sulfate which inhibits tissue factor activity and von Willed brand factor （VWVF） and causes aggregation. Finally this cascade of events cause platelets aggregation and leads to heart ischemia and cardiovascular events. DISCUSSION： Anti-platelet therapy is an interesting premise. Anti-platelet resistance patients and bleeding as a result of using ticagrelor and prasugrel should be considered in this treatment methods. Anti-platelet drugs such as clopidogrel are prescribed in cardiovascular events. Platelets have VWF receptors and P2Y12 receptors on their surface, and thus, targeting these receptors can be useful in treatment. The active metabolites of clopidogrel bind to P2Y12R and inhibit ADP binding; thus, clopidogrel inhibits aggregation by interfering in several events as a result of the inhibition of ADP attachment to P2Y12R of the platelet. However, the polymorphisms of P2~ 12 and other genes mentioned in Table 1 showed treatment resistance in anti-platelet therapy, highlighting that these SNPs can be helpful in anti-platelet therapy. CONCLUSION： The knowledge of these SNPs may decrease the number of unwanted effects that endanger patients with cardiovascular diseases and avoids ineffective anti-platelet therapy in several patients. Clopidogrel, ticagrelor, prasugrel, and aspirin and CYP2C19 and their SNPs are very important subjects in anti-platelet therapy. To present the importance of using phannacogenetics in anti-platelet therapy, we discuss here the association between these drugs and the SNPs for therapeutic resistance.

Threatening biomarkers in lupus pregnancy： Biochemistry and genetic challenges

OBJECTIVES： Using genetic markers and miRs work strongly beside other sensitive biomarkers in lupus management during sensitive period of pregnancy. METHOD： PubMed and Google Scholar databases were searched from 2000 to 2017 using the terms ＂lupus,＂ ＂lupus pregnancy, biomarkers,＂ ＂micro-RNA,＂ ＂polymorphisms,＂ ＂anti-phospholipid antibodies,＂ and ＂cluster differentiation markers,＂ DISCUSSION： Complement is a valuable biomarker in lupus pregnancy. However, the complement profile has ambiguous meaning because decreased levels of C3 and C4 reflect inflammation and because they are also prognostic biomarkers for abortion. Furthermore, increased C3 and C4 levels indicate hepatic protein synthesis in hepatocytes. Anti-phospholipid （APL） antibodies are present in 25% to 50% of lupus patients, and can lead to thrombotic and obstetric complications in some pregnancies and increase the risk of abortion, especially in a pregnant woman in the active phase of lupus. Several studies have associated APL with HELLP syndrome. However, other pregnancy complications have not been associated with APL. Autoantibodies against the major vault protein and anti-double strand DNA antibodies are valuable biomarkers in evaluating lupus activity. The expression pattern ofmicro-RNAs （miRs） differs in various diseases. Current studies have demonstrated the potential of miRs as diagnostic and prognostic biomarkers in various diseases; for example, the level of miR-126 is higher in lupus. CONCLUSION： miR-223-3p and miR-451 are informative biomarkers in estimating disease activity. TWEAK, BAFF, and APOL1 genes, and their polymorphisms are informative in estimating disease activity, especially renal effects, and in monitoring higher-risk pregnant women. Further studies of these genes and their relevant polymorphisms are needed.

How to manage rheumatoid arthritis according to classic biomarkers and polymorphisms？

OBJECTIVES： Single nucleotide polymorphisms （SNPs）, genetic background, and epigenetics play important roles in rheumatoid arthritis （RA）. These factors can be useful in RA diagnosis, prognosis, and treatment response evaluation, particularly with the growing trends in personalized medicine. Therefore, categorizing classic genes and SNPs in RA can present an appropriate guideline for RA management. DISCUSSION： Prognostic and diagnostic biomarkers play important roles in RA diagnosis and treatment. Categorizing SNPs is not an easy process yet, but selecting classic SNPs can be useful worldwide, according to basic similarities that exist in genomes. In this review, we compiled some of these RA-associated SNPs and biomarkers in a table, according to newly identified factors. The role of epigenetics in RA is undeniable; using epigenetic biomarkers like histone deacetylase （HDACs） can be useful in RA diagnosis and treatment, miRs such as miR-146a, miR-155, and miR-222 are useful in diagnosis and can be used in treatment by interfering with other factors＇ functions. Interleukins （ILs） seem to be good prognostic and diagnostic markers and can be targeted in RA treatment. CONCLUSION： Using multiple types of biomarkers, such as useful in RA management and treatment. PTPN22, HLA-DR genes, SNPs, and epigenetic biomarkers like HDACs can be polymorphisms, miRs, and HDACs are considerable in RA susceptibility; hence, they can be valuable biomarkers in future studies. This article gathered separate information from approximately 100 articles to present useful biomarkers and polymorphisms in one review.