Pharmacogenomics is the study of how genetic makeup determines the response to a therapeutic intervention. It has the potential to revolutionize the practice of medicine by individualisation of treatment through the use of novel diagnostic tools. This new science should reduce the trial-and-error approach to the choice of treatment and thereby limit the exposure of patients to drugs that are not effective or are toxic for them. Single Nucleotide Polymorphisms (SNPs) holds the key in defining the risk of an individual's susceptibility to various illnesses and response to drugs. There is an ongoing process of identifying the common, biologically relevant SNPs, in particular those that are associated with the risk of disease. The identification and characterization of large numbers of these SNPs are necessary before we can begin to use them extensively as genetic tools. As SNP allele frequencies vary considerably across human ethnic groups and populations, the SNP consortium has opted to use an ethnically diverse panel to maximize the chances of SNP discovery. Currently most studies are biased deliberately towards coding regions and the data generated from them therefore are unlikely to reflect the overall distribution of SNPs throughout the genome. The SNP consortium protocol was designed to identify SNPs without any bias towards these coding regions. Most pharmacogenomic studies were carried out in heterogeneous clinical trial populations, using case-control or cohort association study designs employing either candidate gene or Linkage disequilibrium (LD) mapping approaches. Concerns about the required patient sample sizes, the extent of LD, the number of SNPs needed in a map, the cost of genotyping SNPs, and the interpretation of results are some of the challenges that surround this field. While LD mapping is appealing in that it is an unbiased approach and allows a comprehensive genome-wide survey, the challenges and limitations are significant. An alternative such as the candidate gene approach does offer several advantages over LD mapping. Ultimately, as all human genes are discovered, the need for random SNP markers diminishes and gene-based SNP approaches will predominate. The challenges will then be to demonstrate convincing links between genetic variation and drug responses and to translate that information into useful pharmacogenomic tests.
Thalassaemia is a hereditary blood disorder that is becoming a major health problem all over the world. This chronic illness harms the quality of life of the sufferers by interrupting their physical activities, school performance and social life. Hence, this review takes aim to assess the factors affecting the quality of life of thalassaemia among paediatrics patients. A comprehensive electronic search was conducted by using PubMed, Google Scholar and Science Direct. The search was limited to those articles written in English language and by using Pediatrics Quality of Life Inventory (PedsQLTM) 4.0 generic core scale questionnaire only. This review notifies emerging knowledge regarding the factors affecting the quality of life among thalassaemia patients and its implications in the essential core domains for paediatrics health-related quality of life measurements: physical, emotional, social and school functioning. It also empowers a better understanding regarding thalassaemia and assists as a foundation for the development of the effective preventive strategies for it.
Colorectal cancer (CRC) is one of the most common cancer worldwide with approximately 2 to 5% of all colon cancers are associated with well-defined hereditary factors. Hereditary nonpolyposis colorectal cancer (Hereditary Nonpolyposis Colorectal Cancer), also known as Lynch syndrome (LS), is the most common form of hereditary CRC characterized by an early age of onset and follows the autosomal dominant inheritance pattern. HNPCC is caused by the alteration in four mismatch repair (MMR) genes. Immunohistochemistry (IHC) and microsatellite instability (MSI) testing, followed by conventional Sanger sequencing reliably identify the majority of mutations. However, methods to identify other underlying variants or genomic rearrangements of HNPCC have emerged. In addition to the clinical characterization and evaluation of HNPCC patients, the implementation of screening strategies for both affected and unaffected CRC patients together with the accelerated advancement in molecular testing methods will shed light on a more comprehensive detection of HNPCC. In this review, the approaches for the selection of high-risk HNPCC and molecular testing performed over the past few years are discussed.
Thalassaemia is a life-long illness that exists globally. The quality of life of adolescents with thalassaemia could differ based on the health policies of a specific region, existing levelof socio-economic development and the illness related variables. This study examines the relationship between socio-demographic and disease-related variables with the quality of life among adolescents with thalassaemia involving multiple treatment centers spread throughout various locations in Malaysia. Participants included 218 adolescents (male=108; female 112) with mean age of 13.86 (SD=2.40). They completed the questionnaire consisting of demographic information, illness-related variables, and Pediatric Quality of Life Inventory 4.0 (PedsQL). The participants in this study was found to have higher total summary score (Mean = 69.64, SD = 14.03), psychosocial health (Mean = 70.23, SD = 14.91), emotional (Mean = 72.12, SD = 20.66), social (Mean = 79.82, SD = 17.37), and school (Mean = 58.69, SD = 16.77) functioning but with lower physical health (Mean = 68.50, SD = 17.22) as compared to previous study that was done in Kuala Lumpur. Findings also shows a significant positive correlation between level of education and frequency of hospitalization (r = .156, p < 0.05), frequency of transfusion (r = .152, p < 0.05), and physical health (r = .186, p < 0.01). An increase in the frequency of transfusion was found to significantly increase social functioning (r = .137, p < 0.05). Other significant correlations are discussed in addition to the quality of life experienced by patients with thalassaemia in different region of theworld.
Wan Khairunnisa Wan Juhari, Khairul Bariah Ahmad Amin Noordin, Wan Faiziah Wan Abdul Rahman, Andee Dzulkarnaen Zakaria, Ahmad Shanwani Mohd Sidek, Muhammad Radzi Abu Hassan, et al.
Background: Hereditary nonpolyposis colorectal cancer (HNPCC) also known as Lynch syndrome is commonly caused by genetic alterations in any of the four mismatch repair (MMR) genes; MLH1, MSH2, MSH6 and PMS2. This is the first study aimed to investigate genetic variants in Malay HNPCC families. Methods: Six Malay HNPCC families who fulfilled any of the Bethesda criteria were recruited into this study. A total of 3 ml of blood was withdrawn from each patient in the families. The samples were further analyzed using polymerase chain reaction and direct sequencing of the selected exons of MLH1 and MSH2 genes. Results: Two missense mutations and four single nucleotide polymorphisms (SNPs) were identified in six patients. These variants in the MLH1 and MSH2 genes were identified in four families who met the revised Bethesda guidelines. In two families, no mutation and polymorphism was identified in both the exon and intron of the respective genes. Of the mutations and polymorphisms identified, five have never been reported in Malay HNPCC families before. A missense mutation was detected in exon 5 of the MLH1 gene, c.394G>C (p.Asp132His) and four mutations and polymorphisms were detected in the MSH2 gene; heterozygous c.211+98T>C and c.211+9C>G and homozygous c.211+98T>C and c.211+9C>G, c.367-86A>C and c.382C>G. Conclusion: The results represented a new spectrum of mutations and polymorphisms in the Malay HNPCC families. However, a larger study involving additional families and analysis is required to determine the impact and nature of the identified mutations and polymorphisms.
Using genome-wide case-control association approach, the current study aimed to determine whether genetic polymorphism(s) is/are associated with H. pylori infection among ethnic Malays from the north-eastern region of Peninsular Malaysia, a region with an exceptionally low prevalence for H. pylori infection and gastric cancer.
INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) has emerged as a major clinical public health threat and challenges the national TB control program in Malaysia. Data that elaborates on the risk factors associated with the development of MDR-TB is highly limited in this country. This study was aimed to determine the risk factors associated with the development of MDR-TB patients in peninsular Malaysia.
METHODOLOGY: This was a case control study; the data were collected from medical records of all the registered MDR-TB patients at five referral TB hospitals in peninsular Malaysia from January 2010 to April 2014. The 105 cases were all confirmed by a positive sputum culture of Mycobacterium tuberculosis for MDR-TB and extensively drug-resistant (XDR)-TB. As a comparison, a total of 209 non-MDR-TB cases were randomly selected as controls.
RESULTS: A total of 105 MDR-TB and 209 non MDR-TB patients were studied. The risk factors associated with MDR-TB within the multivariate analysis were previous tuberculosis treatment, HIV infection, being an immigrant, and high load of positive for acid-fast bacillus (AFB) smear.
CONCLUSIONS: The findings of this study revealed that patients who had received previous treatment for tuberculosis, were infected with HIV, were immigrants, and had a high burden of positive testing for AFB smear were more likely to have MDR-TB. An enhanced understanding of the risk factors associated with MDR-TB strains is imperative in the development of a national policy for public health interventions.