فصلنامه کومش
سال بیست و چهارم شماره 2 (پیاپی 88، فروردین و اردیبهشت 1401)

Personalized medicine (PM) refers to a set of medical, diagnostic, and therapeutic activities and approaches based on the specific characteristics of each patient chr ('39')s genome. In fact, individual-centered medical approaches are based on personalization, meaning that each person chr ('39')s gene sequence and polymorphisms (SNPs) are different and explain the different courses of urological cancers and the different efficiencies of individuals in a protocol. The treatment is constant. Based on data from the Human Genome and Gene Sequence Project, along with proteomics, metabolomics, and transcriptomics information, a number of molecular biomarkers are suggested as potential targets for guided cancer therapies. In urological malignancies, the expression and clinical significance of carbonic anhydrase in type IX in the bladder, kidney, and urinary tract cancers and the primary therapeutic approaches have been discussed. Prostate membrane antigen and radiolabeled analog neuropeptide receptors for prostate cancer are considered valuable prognostic factors in clinical trials. The results of the treatment of patients with urological cancers from a person-centered medical perspective will impose a lower cost on the patient and more effective treatment, which we will discuss in this article

One of the most widely used anti-diabetic drugs is sulfonylureas, which is often used as one of the first-line drugs in the treatment of type 2 diabetes. Due to the effect of the patient's genetic structure on the drug response (personalized medicine), the identification of genetic variations not only reduces the rate of adverse drug reactions but can also predict the effectiveness of drugs. This study aimed to systematically review the pharmacogenomics of glibenclamide in type 2 diabetes.

This systematic review was performed based on PRISMA flowchart. Using the search terms including "variant", “sulfonylurea”, "glibenclamide", "diabetes mellitus", "SNP" or their equivalents, a comprehensive search of the PubMed, Scopus and Web of Science databases was conducted until January 1, 2021. An initial search yielded 125 articles.

Finally, in nine articles included in this systematic review, glibenclamide monotherapy was performed in 3032 patients. Most studies were conducted in China and the most common methods of genotyping were RFLP-PCR and direct sequencing. The most common genes studied were CYP2C9, KCNJ11 and TCF7L2. The results of studies showed a significant effect of CYP2C9 polymorphism on appropriate therapeutic response and KCNJ11 gene polymorphism on failure of glibenclamide treatment.

Among all genetic factors and specific genotypes of proteins involved in the metabolism of glibenclamide, CYP2C9 gene polymorphism has a role in proper response to treatment and KCNJ11 gene polymorphism has a role in treatment failure and hypoglycemic effects of glibenclamide.

Considering an individual’s characteristics such as genetics along with other characteristics and dietary habits can help to provide an effective diet for prevention and controlling metabolic disorders. Accordingly, in the present study, we aimed to review evidence on personalized nutrition (PN) and its roles in metabolic disorders.

In the present narrative review, publications on PN and metabolic disorders published between 2010 and 2020 using PubMed, Scopus, and Google Scholar were searched and collected.

Our findings showed positive effects of precision medicine and PN on controlling metabolic disorders, diabetes, postprandial glucose level, obesity, and lipid profile. Interactions of genetic differences, lifestyle, microbiota patterns, and behavioral and psychological characteristics can affect developing and controlling diseases.

Due to the effects of genetics, gut microbiota, and other individual characteristics in designing and providing a suitable diet, paying attention to PN in the prevention and controlling metabolic disorders is important. PN vs. general dietary recommendations or diet can be more effective; although it needs high expenditure and more equipment.

Nowadays, metabolomics studies are performed with different approaches to identify biomarkers, clarify the underlying mechanisms of diseases and achieve novel treatment strategies. In this context, gut microbiota-derived metabolites are known as one of the most important mediators of gut microbiota effects on human health and various diseases. Due to the inefficiency of conventional therapies in some cases, personalized medicine is of great clinical importance. Recent studies have shown that alterations in gut microbiota metabolites like short-chain fatty acids (SCFAs), amino acids, bile acid metabolites, and choline metabolites can link gut microbiota to numerous chronic non-communicable diseases including obesity, diabetes, inflammatory bowel diseases, psychological disorders, cardiovascular diseases and cancers. Understanding the composition of gut microbiota and the relationship between its derived-metabolites and the occurrence of various diseases is necessary to achieve new clinical applications. Furthermore, potential therapeutic agents such as prebiotic supplements and next-generation probiotics, dietary interventions, antibiotics, and fecal microbiota transplantation (FMT) could be among the leading strategies for personalized medicine in prognosis, diagnosis and treatment of various diseases, via modulating the diversity and composition of gut microbiota and its metabolites.

Cardiovascular diseases are the leading cause of mortality each year. Both environmental and genetic risk factors significantly influence the incidence and progression of these diseases. In recent decades, with the development of genetics and genome-determining tools, different genes have been found associated with numerous diseases. Determining these genes helps us to suggest a more effective treatment, specifically for each individual. Determining the genes involved in each disease, finding them in patients, and finally, treatment based on them are the main goals of personalized medicine. Another achievement of personalized medicine is determining the drug's efficiency and side effects in individuals. In particular, one of the most common drug side effects is bleeding from Warfarin. This complication can be prevented by accurately determining the required dose in each person. Personalized medicine is able to suggest the most appropriate dose by identifying genes involved in drug metabolism and detecting them in patients. In this review study, we examine the genes involved in cardiovascular disease as well as the drugs used in this field. Personalized medicine has a special role in determining the prognosis, risk factors and the most effective type of treatment for each disease. One of the main challenges in this field is finding precise diagnostic tools to find the most accurate gene and determine the patients who can benefit most from personalized medicine.

The approach of personalized medicine has received a great deal of attention over the last century, emphasizing attention to the patient rather than the disease. Personalized medicine tries to plan the patient's condition and treatment method by considering the culture, personal preferences and experiences and health beliefs of the person as well as the values and lifestyle of the person, and even considering the psychosocial condition. Acknowledging the lack of knowledge of traditional medicine such as Persian, Chinese and Ayurvedic medicine about "Omixes", it can be argued that these medical paradigms have been emphasizing individual differences and their relationship with health for thousands of years. Many people know Iranian medicine as the famous theory of temperaments and quadrant humor. Without entering into a philosophical fallacy about the abrogation or obsolescence of this theory, from a practical point of view, it should be said that the separation of human beings and attention to their inherent differences and consequently the same functions and responses of their bodies, whether congenital (Intrinsic temperament) and whether under the influence of extrinsic and environmental factors (acquired temperament) is the basis of this thinking. Therefore, every human being, in turn, is an independent book that is influenced by his inner and outer and all direct and indirect biological factors of his life, and the spectrum of his health and illness is defined in this framework. In this study, the relationship between traditional persian medicine and personalized medicine has been studied.

Genetics, cellular and molecular medicines are cutting-edge sciences and technologies that play an important role in improving human health and quality of life. In addition, medical and biological sciences have clearly shown that the onset of diseases differs from person to person due to their different genetic profiles and variations in molecular basis. Therefore, it is feasible that patients respond differently to a single treatment. Personalized medicine is a new field of medicine aims to tailor medical treatments to the individual characteristics of patients. In this review, in addition to genomics and personalized medicine, we touch upon common techniques in this field and the future of personalized medicine. With this development, people can get more information about the possibility of contracting diseases like cancer and early-stage treatments as well as personalized therapies based on their genetic characteristics. Technologies, such as mutation detection in the genome, microarrays or microchips, and next-generation sequencing of the human genome, have not only made molecular detection better and easier but also facilitated the integration of molecular detection with targeted drug delivery for the development of novel personalized treatment.

Precision medicine, the selection of treatment based on the genetic characteristics of patients, is one of the new paradigms of medical science. Using genetic characteristics and biomarkers, patients' response to different treatments is evaluated and finally, a specific one is selected for them. In other words, using genetic information or biomarkers, the safety, effectiveness and outcomes of treatments are evaluated and then decisions are made for the best method of prevention or efficient treatment. In recent decades, precision medicine has been focused and placed beyond laboratory knowledge in health services and policies. Besides, the tendency to apply this approach has increased due to the ineffectiveness and unsafety of all available medicines. The main issue of precision medicine is a targeted treatment approach based on pharmacogenetic tests. Performing such tests by checking for the presence or absence of specific biomarkers, when prescribing a drug or medication regimen, will help to increase the effectiveness of treatment and prevent adverse drug reactions during therapy. The present article reviews the types of medicines in Iran drug list (the official list of drugs in the country) that have biomarkers and require pharmacogenetic tests. In addition, this article points out the importance of applying these tests in cases other than determining the drug indication.

Type 2 diabetes (T2D) is chronic health caused by the interaction between genetic and environmental factors that results in high blood glucose. The evidence-based guidelines for diabetes management are mainly based on lifestyle changes, control of risk factors, and the management of blood glucose levels. Although numerous antidiabetic agents have been developed over time, T2D treatment should be based on the patient's genomic characteristics. In the present study, we review genetic variations that may be responsible for a common therapeutic response in diabetes.

The treatment of T2D is discussed in the perspective of a pharmacogenomic approach by searching for related studies on PubMed, Scopus, Web of Sciences (WoS), and Scholar databases.

Among the antidiabetic drugs used in T2D treatment, the association of six drugs, including metformin, sulfonylurea, meglitinide, DPP4 inhibitors, SGLT-2 inhibitors, and Thiazolidinedione's with commonly related genes in responding to the drugs was found among the studies.

Pharmacogenomics studies investigate the role of genomic variations in drug efficacy and toxicity. The finding of genetic factors that modulate the glycemic response may provide a new way to T2D treatment and may ultimately advance the development of precision medicine therapy. Early diagnosis and appropriate treatment can reduce the severity of diabetes and its related complications.

Pharmacogenomics may well have substantial effects on the clinical, economic and regulatory aspects of health sector; which can lead to complications in access. Therefore, there is a need for evidence-based frameworks based on national drug policy components. The objective of the current study is to identify pharmacogenomics-based complications and develop a conceptual model.

The current, is an applied-quantitative study using soft system methodology. The first step adopted scoping review with systematic-search to identify early-adopters experiences. The second used cognitive mapping technique with strategic options development and analysis method using expert panels to assess the relativeness of the challenges and evaluated influence with interpretive structural modeling. In addition, stakeholder mapping was conducted using semi-structured questioners. The third step is used to develop the conceptual model.

Systematic search acknowledged 82 studies for qualitative analysis on the challenges. The identified challenges, which were confirmed by the experts subsequently, were clinical trial protocols, clinical utility of tests and identifying biomarkers in the efficacy/safety component, pricing, coverage and economic assessment in the affordability component, regulations, availability and stakeholders management in the access component and education, guidelines, patient compliance, information technology, bench-to-bedside strategies and ethical/legal/social hazards in the rational use of medicine component. The most influential issue was biomarker validity. The main stakeholder, as the owner and customer, was identified to be the ministry of health. All the results were included in the complicated conceptual model.

The current, was the first study identifying dynamic complications ahead of pharmacogenomics adoption, using soft system methodology. The results may be the basis of the first evidence-based policy on pharmacogenomics, in Iran and other developing countries.

Psychiatric disorders are important health issues in the world, and their management is facing some serious challenges. Drugs that are widely used in the treatment of psychiatric disorders, including antidepressants, antipsychotics, and mood stabilizers, are often associated with many side effects and are adequately effective only in a small proportion of patients. Many factors, including genetic factors, affect the effectiveness of medications prescribed for mental health disorders.  Pharmacogenetics is the study of the association between genetic variations in genes encoding carriers, receptors, and drug-metabolizing enzymes with drug response. Many genes have been identified as affecting the drugs responsible for psychiatric disorders and genetic variation can lead to variations in the efficacy and side effects of drugs. This review article summarizes some psychiatric drugs and related genes, which could have potential functional effects.

Vitamins are important micronutrients and are often precursors of enzymes that living cells need to perform biochemical reactions. Because humans cannot biosynthesize most vitamins, therefore, they must be obtained exogenously. Although a variety of vitamins are found in most foods, many people's vitamin deficiencies still occur mainly due to malnutrition as a result of inadequate food consumption or poor eating habits. In this review article, the potential of lactic acid (LAB) and bifidobacteria probiotics is investigated as an inexpensive and terminating solution to this problem. Probiotics can produce important vitamins in the microbiome, including vitamin A, vitamin D, vitamin K, vitamin B12, and so on. Therefore, increasing the ratio of probiotics in the microbiome is one of the important ways to eliminate vitamin deficiency. The gut microbiome plays an important role in health and disease as personalized medicine. The results also showed that Lactobacillus reuteri and L. rhamnosus could be the best choices for producing a set of vitamins needed by a person in terms of diversity by producing B‐group vitamins, vitamin K2 and vitamin D.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders and causes 75% of infertility due to ovulation disorders in reproductive age. Women with PCOS have oligomenorrhea and hyperandrogenism that affect their quality of life and fertility at the same time. This syndrome has been one of the most controversial endocrine issues for many years. Research today suggests that PCOS is an inherited disease and that genes are involved in transmission to the next generation. The results of this study, which was performed on thousands of women around the world, show that the expression of some genes has changed. The genes that have been studied are responsible for the synthesis and regulation of steroid hormones, the regulation of gonadotropins, and the synthesis and function of insulin. Although the underlying cause of pathogenesis is not yet known, there is evidence for the role of genetic factors, lifestyle, nutrition, and environmental pollution in the development of the disease. Therefore, it is hoped that the treatment of this heterogeneous syndrome will improve with the help of personalized medicine. Further studies are needed to determine the association between the various factors that may play an active pathogenic role in PCOS.