Review on Gene polymorphism
Department of Pharmaceutical Analysis, MGR Medical University, Chennai, India
- *Corresponding Author:
- Priyanka R
Department of Pharmaceutical Analysis, MGR Medical University, Chennai, India
Received Date: 16/05/2015; Revised Date: 19/05/2015; Published Date: 31/05/2015
Visit for more related articles at Research & Reviews: Journal of Pharmacology and Toxicological Studies
Review on Gene polymorphism
Gene polymorphism is distinction in DNA sequence among individual patients, groups, or populations. Sources like SNPs, sequence repeats, insertions, deletions and recombination [1-4]. Genetic polymorphism is also the result of chance processes, or might have been induced by external agents (such as viruses or radiation) [5-8]. If deference in DNA sequence among patients has been shown to be related to disease, it will sometimes be known as genetic mutation. Changes in DNA sequence that are confirmed to be caused by external agents are typically known as "mutations" instead of "polymorphisms” [9-14].
Genetic mutations are a form of genetic polymorphism. Genetic mutation is a permanent alteration within the polymer sequence that produces up a gene, specified that the sequence differs from what is found in majority of individuals [15-19]. Mutations will have an effect on anywhere from one polymer (DNA) building block (base pair) to an oversized phase of a chromosome that features multiple genes [17,20-23].
Single nucleotide polymorphism may be a single base mutation in Deoxyribonucleic acid and SNPs are the common source of genetic polymorphism [24-27]. Genetic polymorphisms of CYP2C9 and CYP2C19 are shown to have clinical consequences leading to toxicity of some medicine within the affected individual, and will alter efficacy of alternative medicine [28-31].
Polymorphism in drug‐metabolising enzymes plays importance for interindividual variations in drug medical care. Variant genes inflicting hyperbolic, diminished or abolished drug metabolism influences the drug response and risk for adverse drug reactions [29,32]. The genetic alterations embody single‐ nucleotide polymorphisms and gene copy number variations. This variability is currently significance throughout drug development and of importance for routine drug prescription. There are many different drugs contain pharmacogenomic labels where genotyping before prescription is necessary or recommended. Predictive genotyping of drug‐metabolising genes can thus help to design individualised, safer and a lot of economical drug therapies [33-35].
Genetic variation or polymorphisms in the miRNA pathway are related to the prognosis and progression of diseases and drug responses and are increasing as powerful tools to review the biology of diseases [36,37]. MicroRNA polymorphisms might probably interfere with miRNA‐mediated regulation of cellular functions and may available not only in the miRNA target gene but also in pri‐, pre‐, mature‐miRNA sequences, in the genes involved in miRNA biogenesis and in miRNA cis‐regulatory components. The invention of the role of miRNA in drug resistance and miR‐polymorphisms to predict drug response results to the development of a new branch in biomedical science called miRNA pharmacogenomics [38-40]. Detection of miRNA‐polymorphisms will probably improve detection, treatment and prognosis in patients and has profound implications within the fields of pharmacogenomics and personalised medicine.
Pharmacogenetics is concentrated on pharmacological consequences of a single chromosomal mutation, pharmacogenomics tries to at the same time contemplate various genes and their mutual interaction . Genotyping for CYP polymorphisms provides necessary genetic information that facilitates to understand the results of xenobiotic on human body. For drug metabolism, the main important polymorphisms are those of the genes coding for CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5, which can result in therapeutic failure or severe adverse reactions . Genes coding for CYP1A1, CYP1A2, CYP1B1, and CYP2E1 are among the foremost liable for the biotransformation of chemicals, particularly for the metabolic activation of pre-carcinogens.
The toxicity of medicine due to genetic polymorphism is major issue in pharmaceutical products development and clinical use. Pharmacogenetics is that the study of genetically controlled variations in drug response . Gene polymorphism includes monogenic variation due to gene variation at a single gene, polygenic is due to the variation happened at two or more genes.
Polymorphisms of genes concerned in innate and adaptive immunity have become an object of major interest in regard to hematopoietic stem cell transplantation (HSCT) complications. Vitamin D receptor (VDR) gene polymorphisms and the risks for various breast and ovarian cancers have been reported in many epidemiological studies. SNPs occur normally throughout a person’s DNA. They act as biological marker to find out the genes that are associated with disease . SNPs are produced within the gene or near to the regulatory region of a gene and acts as major role in disease by causing harmful to the gene’s function. Researchers have found SNPs that may help predict an individual’s response to certain drugs, susceptibility to environmental factors such as toxins, and risk of developing particular diseases.
Genetic polymorphisms of drug-metabolizing enzymes make to distinct subgroups within the population that differs in their ability to perform bound drug biotransformation reactions. Polymorphisms area unit generated by mutations within the genes for these enzymes, that causes slashed, increased, or absent accelerator expression or activity by multiple molecular mechanisms [18,24,44]. Genetic polymorphisms are represented for a large type of drug and xenobiotic metabolizing enzymes.
Genetic polymorphism has been coupled to 3 categories of phenotypes supported the extent of drug metabolism. in depth metabolism (EM) of a drug is characteristic of the conventional population; poor metabolism (PM) is related to accumulation of specific drug substrates and is typically an autosomal recessive trait requiring mutation and/or deletion of both alleles for phenotypic expression; and ultra- extensive metabolism (UEM) results in increased drug metabolism and is an autosomal dominant trait arising from gene amplification . The main reason for interindividual variation of drug effects is genetic variation of drug metabolism.
Extreme genetic polymorphism maintained by equalization choice (so referred to as a result of several genes area unit maintained in a very balance by a mechanism of rare allele advantage) is intimately related to the vital task of self/non-self-discrimination. Wide disparate self-recognition systems of plants, animals and fungi share many general options, together with the upkeep of enormous numbers of alleles at comparatively even frequency, and persistence of this variation over terribly long term periods . Due to the evolutionary dynamics of balanced polymorphism are very different from those of neutral genetic variation, data on balanced polymorphism have been used as a novel source for inference of the history of populations.
I would like to acknowledge the support of my colleagues Rakesh M, Sateesh V in assisting with proper guidance. This content is reviewed and approved by Murali M.
- Borges JB, et al. Polymorphisms in Genes Encoding Metalloproteinase 9 and Lymphotoxin-Alpha can Influence Warfarin Treatment. J Pharmacogenomics Pharmacoproteomics. 2015; 6: 143.
- Ishii M, et al. A Cyclooxygenase 2 Gene Polymorphism is a Risk Factor for the Complication of Medication Overuse Headaches in Patients with Migraines. J Neurol Disord. 2015; 3: 206.
- Vattam KK, et al. Importance of Gene Polymorphisms in Renal Transplant Patients to Prevent Post Transplant Diabetes. J Diabetes Metab. 2014; 5: 463.
- Qiu Y, et al. Intracellular Adhesion Molecule-1 K469E Gene Polymorphism and the Risk of Inflammatory Bowel Disease: A Meta-Analysis. Immunome Res. 2014; 10: 082.
- Jahromi M, et al. Critical Association Study of Olfactory Receptor Gene Polymorphism in Diabetic Complications. Immunome Res. 2014; 10: 079.
- Rod A, et al. ESR1 and FSHR Gene Polymorphisms Influence Ovarian Response to FSH in Poor Responder Women with Normal FSH Levels. Endocrinol Metab Synd. 2014; 4:141.
- Das D and Haloi A. Vitamin B12 Gene Polymorphisms and Chronic Diseases. J Nutr Disorders Ther. 2014; 4:149.
- Younes AKH, et al. Lack of Association between Catalase Gene Polymorphism and Susceptibility to Vitiligo in an Egyptian Population. Pigmentary Disorders. 2014; 3: 124.
- Khalil O, et al. Does Resistin Gene Polymorphisms +299 (G>A) Participate in Insulin Resistance in Egyption non-Obese Type 2 Diabetes? Int J Genomic Med. 2014; 2: 117.
- Liu Z, et al. The Association Study of PRKG1 Gene Polymorphism and Salt-Sensitive Hypertension among the Essential Hypertension in Beijing. J Hypertens. 2014; 3: 162.
- Rinaldi C, et al. PON I and GLO I Gene Polymorphisms and Their Association with Breast Cancer: A Case-Control Study in a Population from Southern Italy. J Mol Biomark Diagn. 2014; 5: 170.
- Berkinbayev S, et al. Apolipoprotein Gene Polymorphisms (APOB, APOC111, APOE) in the
Development of Coronary Heart Disease in Ethnic Groups of Kazakhstan. J Genet Syndr Gene Ther. 2014; 5: 216.
- Banerjee BD, et al. Assessment of Toxicogenomic Risk Factors in Etiology of Preterm Delivery. Reprod Syst Sex Disord. 2014; 3: 129.
- Zhao J, et al. Analysis of TNF-β, IL-10, and IL-1 Cluster Gene Polymorphisms and Clinical Risk Factors on Acute Renal Graft Rejection. Intern Med. 2013; 3:129.
- Toraldo DM, et al. Frequency of Human Leukocyte Antigens, Plasminogen Activator Inhibitor-1 and Methylenetetrahydrofolate Reductase Gene Polymorphisms in Obstructive Sleep Apnea- Hypopnea Syndrome with or without Pulmonary Artery Hypertension. J Sleep Disorders Ther. 2013; 2:131.
- Mormile R and Vittori G. Endometriosis and Susceptibility to Cancer: The Dark Side of IFN-? Gene Polymorphism? J Cancer Sci Ther. 2013; 5: 289-290.
- Dholariya S, et al. TP53 Gene Polymorphism in Epithelial Ovarian Carcinoma Patients from North Indian Population and its Pro/Pro Variant is Potentially Contributing to Cancer Susceptibility. J Genet Syndr Gene Ther. 2013; 4:145.
- Shajithanoop S, et al. The Serotonin Receptor 2a (Ser 2a) Gene Polymorphism and its Association with Obesity and Dyslipidemia in Semi Urban Subjects of Coimbatore, South India. J Obes Weight Loss Ther. 2013; 3:178.
- Cheema BS, et al. RAS Gene Polymorphisms and Renal Responsiveness to RAS Inhibition Therapy in Type 2 Diabetic Asian Indians. J Pharmacogenomics Pharmacoproteomics. 2013; 4: 114.
- Leu JIJ, et al. The p53 Codon 72 Polymorphism Modifies the Cellular Response to Inflammatory Challenge in the Liver. J Liver. 2013; 2:117.
- Jin W, et al. Association of Bone Morphogenic Protein Receptor IA (BMPIA) Gene Polymorphism with Ossification of Posterior Longitudinal Ligament (OPLL) of the Cervical Spine in a Chinese Han Population. J Spine. 2013; 2: 131.
- Shah VN, et al. Endothelial Nitric Oxide Synthase Gene Polymorphism and the Risk of Diabetic Neuropathy in Asian Indian Patients with Type 2 Diabetes. J Diabetes Metab. 2013; 4:243.
- Zar T, et al. Focal Segmental Glomerulosclerosis Associated Seronegative Antiphospholipid Syndrome. J Nephrol Therapeut. 2012; 2:123.
- Addala L, et al. P53 Codon 72 Gene Polymorphism and Risk of Oral Squamous Cell Carcinoma in South Indian Population: A Case-Control Study. J Cancer Sci Ther. 2012; 4: 188-192.
- Zhang N, et al. Epidemiological Study of AGT Gene Polymorphism among Chinese Subjects with Primary Hypertension. Adv Pharmacoepidem Drug Safety. 2012; 1:110.
- Blum K, et al. Neuropsychiatric Genetics of Happiness, Friendships, and Politics: Hypothesizing
Homophily (“Birds of a Feather Flock Together”) as a Function of Reward Gene Polymorphisms. J Genet Syndr Gene Ther. 2012; 3:112.
- Jurado J, et al. Angiotensin Converting Enzyme Gene Polymorphism as a Genetic Biomarker of Diabetic Peripheral Neuropathy: Longitudinal Prospective Study. J Neurol Neurophysiol. 2011; 2:121.
- Toy WC, et al. Adiponectin Gene Polymorphisms and Type 2 Diabetes among Singaporean Chinese Adults. J Diabetes Metab. 2011; 2:152.
- Muawia S, et al. Association of CD40 Genotyping and its Protein Expression with Airway Inflammatory Diseases. J Mol Biomark Diagn. 2011; 2:115.
- Miranda-Vilela AL and Lordelo GS. Role of Methylenetetrahydrofolate Reductase (Mthfr), Glutathione S-transferases (Gsts M1 and T1) and Haptoglobin (Hp) Gene Polymorphisms in Susceptibility to Chronic Myeloid Leukemia (Cml). J Hematol Thromb Dis. 2013; 1:103.
- Muthuswamy S, et al. Co-existence of CFTR and SPINK1 Gene Mutations in an Idiopathic Chronic Pancreatitis Case. Gene Technology. 2015; 4:116.
- Chung C. Tyrosine Kinase Inhibitors for EGFR Gene Mutation-Positive Non-Small Cell Lung Cancers: An Update for Recent Advances in Therapeutics. J Pharmacovigilance. 2015; 2:155.
- Cai ZX, et al. APC, FBXW7, KRAS, PIK3CA, and TP53 Gene Mutations in Human Colorectal Cancer Tumors Frequently Detected by Next-Generation DNA Sequencing. J Mol Genet Med. 2014; 8:145.
- Wasim M and Fakhar N. Leptin Gene Mutations in Morbidly Obese and Severely Lean Individuals from Punjab, Pakistan. J Obes Weight Loss Ther. 2014; 4: 233.
- Tayyab M, et al. Distinct Gene Mutations, their Prognostic Relevance and Molecularly Targeted Therapies in Acute Myeloid Leukemia (AML). J Cancer Sci Ther. 2014; 6: 337-349.
- Bourthoumieu S, et al. aCGH may be useful in Case of Dominant Disorders known to be caused by Gene Mutations: Two Case Reports. J Mol Genet Med. 2014; 08:115.
- Zemani-Fodil F, et al. Factor 8 Gene Mutations and Risk of Inhibitor Development in Hemophilia A Algerian Patients. J Pharmacogenomics Pharmacoproteomics. 2014; 5:124.
- Kobayashi K and Hagiwara K. Treatment Guideline for Advanced NSCLC Based on Driver Gene Mutations. J Genet Syndr Gene Ther. 2014; 5: 212.
- Nassiri I, et al. Co-occurrence: A Gene Reference Resource for Coincidental Patterns of Gene Mutations in Human Cancers. J Proteomics Bioinform. 2013; 6:197-201.
- Cooper DN. Exploring the Role of Genomic Architecture and the Local DNA Sequence Environment in Mediating Gene Mutations Underlying Human Inherited Disease. J Genet Syndr Gene Ther. 2012; 3: e113.
- Kolnik M, et al. Prevalence of Mefv Gene Mutations and their Association with Clinical Phenotypes in 102 Caucasian Children with Henoch-Schonlein Purpura. Hereditary Genet. 2012; 1: 112.
- Magd MAE, et al. Effect of SNPs in Prolactin Promoter on Milk Traits in Egyptian Buffalo. J Adv Dairy Res. 2015; 3:128.
- Mezzavilla M and Ghirotto S. Neon: An R Package to Estimate Human Effective Population Size and Divergence Time from Patterns of Linkage Disequilibrium between SNPS. J Comput Sci Syst Biol. 2015; 8: 037-044.
- Pawlak-Adamska E, et al. Tagging SNPs in the Excision Repair Cross-Complementing Group 4 (ERCC4) Gene Increased Risk of Cervical Squamous Cell Carcinoma (CSCC) and Modulate the Disease Outcome. J Carcinog Mutagen. 2014; 5:172.
- Iskakova AN, et al. Allele Frequency and Genotype Distribution of 9 SNPs in the Kazakh Population. J Pharmacogenomics Pharmacoproteomics. 2014; 5:129.
- Al-Haggar M. SNPs as Co-morbid Factors for Drug Abuse and Ischemic Heart Disease. Gene Technology. 2014; 3:107.