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  1. Fulltext 40 years of Alma Ata Malaysia: Targeting equitable access through organisational and physical adaptations in the delivery of public sector primary care - CORRIGENDUM
    Fadzil F, Jaafar S, Ismail R
    Prim Health Care Res Dev, 2020 05 21;21:e13.
    PMID: 32434613 DOI: 10.1017/S1463423620000146
  2. Fulltext 40 years of Alma Ata Malaysia: targeting equitable access through organisational and physical adaptations in the delivery of public sector primary care
    Fadzil F, Jaafar S, Ismail R
    Prim Health Care Res Dev, 2020 02 24;21:e4.
    PMID: 32090729 DOI: 10.1017/S146342362000002X
    This paper illustrates the development of Primary Health Care (PHC) public sector in Malaysia, through a series of health reforms in addressing equitable access. Malaysia was a signatory to the Alma Ata Declaration in 1978. The opportunity provided the impetus to expand the Rural Health Services of the 1960s, guided by the principles of PHC which attempts to address the urban-rural divide to improve equity and accessibility. The review was made through several collation of literature searches from published and unpublished research papers, the Ministry of Health annual reports, the 5-year Malaysia Plans, National Statistics Department, on health systems programme and infrastructure developments in Malaysia. The Public Primary Care Health System has evolved progressively through five phases of organisational reforms and physical restructuring. It responded to growing needs over a 40-year period since the Alma Ata Declaration in 1978, keeping equity, accessibility, efficiency and universal health coverage consistently in the backdrop. There were improvements of maternal, infant mortality rates as well as accessibility to health services for the population. The PHC Reforms in Malaysia are the result of structured and strategic investment. However, there will be continuing dilemma between cost-effectiveness and equity. Hence, continuous efforts are required to look at opportunity costs of alternative strategies to provide the best available solution given the available resources and capacities. While recognising that health systems development is complex with several layers and influencing factors, this paper focuses on a small but crucial aspect that occupies much time and energies of front-line managers in the health.
  3. Fulltext A minireview of CYP2C9 and CYP2C19 single nucleotide polymorphisms (SNPs) among Malaysian populations
    Rosdi R.A., Yusoff S., Mohd Yusoff N., Ismail R., Tan, C.S., Musa N.
    Journal of Biomedical and Clinical Sciences, 2017;2(1):47-52.
    MyJurnal
    It has been recognized extensively that studies of pharmacogenetics provide massive examples of causal relationship between genotypes and drug effectiveness to account for interindividual phenotypic variations in drug therapy. In most cases, cytochrome P450 (CYP) polymorphisms are one of the major variables that affecting those drug plasma concentration, drug detoxification and drug activation in humans. Thus, understanding of CYP polymorphisms can be crucially valuable in order to allow early and more accurate drug dosage prediction and improve the drug response accordingly. Despite the high level of homologous amino acid sequences, CYP2C9 and CYP2C19 genes are among the most important CYP genes which metabolize a wide range of clinically therapeutic drugs. Several critical reviews have been published relating to the aforementioned genes. However, this minireview aims to systematically merge reported studies on the SNPs frequencies of both genes concentrating only on Malaysian population. It is hoped that, the minireview can be an opener for new opportunities to reevaluate the evidence on the prevalence of CYP2C genes as a potential genetic factor influencing a particular drug efficacy and safety among Malaysian. Such evaluation can be developed to the next level of early prediction of better and specific drug treatment, thereby improving the drug response while helping the government in minimising the drug expenditures.
  4. Fulltext A Nested Allele-Specific Multiplex Polymerase Chain Reaction Method for the Detection of DRD2 Polymorphisms
    Zahari Z, Salleh MR, Zahri Johari MK, Musa N, Ismail R
    Malays J Med Sci, 2011 Oct;18(4):44-57.
    PMID: 22589672 MyJurnal
    The dopamine D2 receptor gene (DRD2) plays a role in many diseases such as schizophrenia, Parkinson's disease, and addictive behaviour. Methods currently available for the detection of DRD2 polymorphisms are costly and cannot detect all 8 polymorphisms of our research interest simultaneously (Val96Ala, Leu141Leu, Val154Ile, Pro310Ser, Ser311Cys, TaqI A, A-241G, and -141C Ins/Del). Therefore, we developed a nested multiplex polymerase chain reaction (PCR) for simultaneous detection of these polymorphisms.
  5. A Randomized, Single-Blind Trial of Clobetasol Propionate 0.05% Cream Under Silicone Dressing Occlusion Versus Intra-Lesional Triamcinolone for Treatment of Keloid
    Nor NM, Ismail R, Jamil A, Shah SA, Imran FH
    Clin Drug Investig, 2017 Mar;37(3):295-301.
    PMID: 27888448 DOI: 10.1007/s40261-016-0484-x
    BACKGROUND AND OBJECTIVE: Keloid is conventionally treated with intra-lesional (IL) triamcinolone, which is highly operator dependent and has its own adverse effects. Topical steroid and silicone dressings are a patient friendly and non-invasive treatment alternative. We therefore sought to determine the efficacy and safety of topical clobetasol propionate (Dermovate(®)) 0.05% cream under occlusion with Mepiform(®) silicone dressing compared to IL triamcinolone in the treatment of keloid.

    METHODS: This was a prospective, randomised, observer-blinded study. Two keloids on the same site were randomly assigned to receive either daily topical clobetasol propionate 0.05% cream under occlusion with silicone dressing (Scar 1) or monthly IL triamcinolone injection (Scar 2). Efficacy was assessed using patient and observer scar assessment scale (POSAS) at 4-weekly intervals up to 12 weeks. Dimension of keloid and adverse effects were also assessed.

    RESULTS: A total of 34 scars from 17 patients completed the study. There was significant improvement of POSAS at 12 weeks compared to baseline within each treatment group. However, there was no statistically significant difference in POSAS at 12 weeks between the two treatments. Keloid dimensions showed a similar trend of improvement by week 12 with either treatment (p = 0.002 in Scar 1, p = 0.005 for Scar 2). However, there was no significant difference between the treatment. In the IL triamcinolone group, all patients reported pain and 70.6% observed necrotic skin reaction. There was a significantly higher rate of adverse effects such as erythema (41.2 vs. 17.6%), hypopigmentation (35.3 vs. 23.5%), telangiectasia (41.2 vs. 17.6%) and skin atrophy (23.5 vs. 5.9%) documented in the IL triamcinolone group when compared to clobetasol propionate 0.05% cream under occlusion with silicone dressing.

    CONCLUSION: Clobetasol propionate 0.05% cream under occlusion with silicone dressing is equally effective and has fewer adverse effects compared to IL triamcinolone. Hence, it may be used as an alternative treatment for keloid particularly in patients with low pain threshold, needle phobia and those who prefers home-based treatment.

  6. Fulltext A carrier velocity model for electrical detection of gas molecules
    Hosseingholi Pourasl A, Ariffin SHS, Ahmadi MT, Ismail R, Gharaei N
    Beilstein J Nanotechnol, 2019;10:644-653.
    PMID: 30931206 DOI: 10.3762/bjnano.10.64
    Nanomaterial-based sensors with high sensitivity, fast response and recovery time, large detection range, and high chemical stability are in immense demand for the detection of hazardous gas molecules. Graphene nanoribbons (GNRs) which have exceptional electrical, physical, and chemical properties can fulfil all of these requirements. The detection of gas molecules using gas sensors, particularly in medical diagnostics and safety applications, is receiving particularly high demand. GNRs exhibit remarkable changes in their electrical characteristics when exposed to different gases through molecular adsorption. In this paper, the adsorption effects of the target gas molecules (CO and NO) on the electrical properties of the armchair graphene nanoribbon (AGNR)-based sensor are analytically modelled. Thus, the energy dispersion relation of AGNR is developed considering the molecular adsorption effect using a tight binding (TB) method. The carrier velocity is calculated based on the density of states (DOS) and carrier concentration (n) to obtain I-V characteristics and to monitor its variation in the presence of the gas molecules. Furthermore, the I-V characteristics and energy band structure of the AGNR sensor are simulated using first principle calculations to investigate the gas adsorption effects on these properties. To ensure the accuracy of the proposed model, the I-V characteristics of the AGNR sensor that are simulated based both on the proposed model and first principles calculations are compared, and an acceptable agreement is achieved.
  7. A case-control study of influenza vaccine effectiveness among Malaysian pilgrims attending the Haj in Saudi Arabia
    Mustafa AN, Gessner BD, Ismail R, Yusoff AF, Abdullah N, Ishak I, et al.
    Int J Infect Dis, 2003 Sep;7(3):210-4.
    PMID: 14563225
    To determine influenza vaccine effectiveness against clinically defined influenza-like illness among Malaysian pilgrims attending the Haj in Saudi Arabia.
  8. Fulltext A cross-sectional analysis of the PURE study on minerals intake among Malaysian adult population with hypertension
    Mat Nasir N, Md Isa Z, Ismail NH, Ismail R, Mohd Tamil A, Jaafar MH, et al.
    Sci Rep, 2024 Apr 13;14(1):8590.
    PMID: 38615144 DOI: 10.1038/s41598-024-59206-0
    Hypertension (HPT) is the leading modifiable risk factor for cardiovascular diseases and premature death worldwide. Currently, attention is given to various dietary approaches with a special focus on the role of micronutrient intake in the regulation of blood pressure. This study aims to measure the dietary intake of selected minerals among Malaysian adults and its association with HPT. This cross-sectional study involved 10,031 participants from the Prospective Urban and Rural Epidemiological study conducted in Malaysia. Participants were grouped into HPT if they reported having been diagnosed with high blood pressure [average systolic blood pressure (SBP)/average diastolic blood pressure (DBP) ≥ 140/90 mm Hg]. A validated food frequency questionnaire (FFQ) was used to measure participants' habitual dietary intake. The dietary mineral intake of calcium, copper, iron, magnesium, manganese, phosphorus, potassium, sodium, and zinc was measured. The chi-square test was used to assess differences in socio-demographic factors between HPT and non-HPT groups, while the Mann-Whitney U test was used to assess differences in dietary mineral intake between the groups. The participants' average dietary intake of calcium, copper, iron, magnesium, manganese, phosphorus, potassium, selenium, sodium, and zinc was 591.0 mg/day, 3.8 mg/day, 27.1 mg/day, 32.4 mg/day, 0.4 mg/day, 1431.1 mg/day, 2.3 g/day, 27.1 µg/day, 4526.7 mg/day and 1.5 mg/day, respectively. The intake was significantly lower among those with HPT than those without HPT except for calcium and manganese. Continuous education and intervention should be focused on decreasing sodium intake and increasing potassium, magnesium, manganese, zinc, and calcium intake for the general Malaysian population, particularly for the HPT patients.
  9. A facile three-component [3+2]-cycloaddition for the regioselective synthesis of highly functionalised dispiropyrrolidines acting as antimycobacterial agents
    Wei AC, Ali MA, Yoon YK, Ismail R, Choon TS, Kumar RS
    Bioorg Med Chem Lett, 2013 Mar 1;23(5):1383-6.
    PMID: 23352268 DOI: 10.1016/j.bmcl.2012.12.069
    A series of fourteen dispiropyrrolidines were synthesized using [3+2]-cycloaddition reactions and were screened for their antimycobacterial activity against Mycobacterium tuberculosis H(37)Rv in HTS (High Throughput Screen). Most of the compounds showed moderate to good activity with MIC of less than 20 μM. Compound 4'-(4-bromophenyl)-1'-methyldispiro[acenaphthylene-1,2'-pyrrolidine-3',2″-indane]-2,1″(1H)-dione (4c) was found to be the most active with MIC of 12.50 μM.
  10. A simple and rapid genotyping method for beta-2 receptor (beta2 AR) gene using allele specific multiplex PCR
    Romaino SM, Teh LK, Zilfalil BA, Thong CP, Ismail AA, Amir J, et al.
    J Clin Pharm Ther, 2004 Feb;29(1):47-52.
    PMID: 14748897 DOI: 10.1046/j.1365-2710.2003.00535.x
    Polymorphism of the beta2-adrenergic receptor (beta2 AR) gene is an important determinant of the function of this receptor. It affects receptor down-regulation and beta2-agonist responses. It has also been a focus of interest in attempts to elucidate the genetic basis of asthma, hypertension, obesity and cystic fibrosis. Several different techniques have been established to determine beta2 AR genotypes but none of these methods are simple enough to detect simultaneously all the five alleles of our research interest (Arg16/Gly16, -20T/C, Gln27/Glu27, -47T/C and Thr164/Ile164).
  11. A simple method for the detection of CYP2C9 polymorphisms: nested allele-specific multiplex polymerase chain reaction
    Zainuddin Z, Teh LK, Suhaimi AW, Salleh MZ, Ismail R
    Clin Chim Acta, 2003 Oct;336(1-2):97-102.
    PMID: 14500040 DOI: 10.1016/s0009-8981(03)00319-x
    BACKGROUND: Cytochrome P4502C9 (CYP2C9), a principle drug-metabolizing enzyme is polymorphic in humans and is responsible for important pharmacokinetic and pharmacodynamic variations of CYP2C9 substrates. We developed an allele-specific multiplex polymerase chain reaction (PCR) method for the detection of common CYP2C9 alleles.
    METHOD: Genomic DNA was extracted from blood obtained from 40 unrelated healthy Malaysian Indian volunteers. The DNA was subjected to a first PCR that was used to amplify both exons 3 and 7 simultaneously in one reaction tube and a second PCR that was used to detect the polymorphic sites of CYP2C9 alleles using allele-specific primers. Sequencing was performed to validate the test results.
    RESULTS: We were successful in amplifying the fragments of interest from the DNA samples. The method was also reproducible and specific. The amplified sequences showed 100% homology to CYP2C9 sequence.
    CONCLUSION: This is the first nested allele-specific multiplex PCR method reported to allow for the simultaneously detection of five CYP2C9 alleles.
  12. A simple multiplex PCR method for the concurrent detection of three CYP2C8 variants
    Muthiah YD, Lee WL, Teh LK, Ong CE, Salleh MZ, Ismail R
    Clin Chim Acta, 2004 Nov;349(1-2):191-8.
    PMID: 15469873 DOI: 10.1016/j.cccn.2004.06.024
    BACKGROUND: Cytochrome P450 (CYP) 2C8 is a principle enzyme responsible for the metabolism of many clinically important drugs as well as endogenous compounds such as arachidonic acid. The enzyme is genetically polymorphic but a simple method is not available to study its genetic polymorphism. We developed and optimized a variant-specific PCR techniques to detect CYP2C8*2, CYP2C8*3 and CYP2C8*4.
    METHOD: Genomic DNA was extracted from blood using standard extraction methods. A two-step PCR method was developed to detect simultaneously three CYP2C8 variants. In the first PCR (PCR1), specific regions from exons 3, 5 and 8 of the CYP2C8 gene were amplified. The products were used as templates in parallel alleles-specific PCR (PCR2). This method was tested against DNA samples obtained from 57 healthy Malaysian volunteers.
    RESULT: The bands of interest were successfully amplified. This method showed specific and reproducible results when tested on healthy volunteers. DNA sequencing further confirmed genotype results obtained from current method.
    CONCLUSION: We have successfully developed and optimized a multiplex PCR method suitable for use in population studies of CYP2C8 polymorphism.
  13. ABCB1 Polymorphisms and Cold Pressor Pain Responses: Opioid-Dependent Patients on Methadone Maintenance Therapy
    Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.
    Nurs Res, 2017 Mar-Apr;66(2):134-144.
    PMID: 28252574 DOI: 10.1097/NNR.0000000000000204
    BACKGROUND: Methadone is a substrate of the P-glycoprotein efflux transporter, which is encoded by ABCB1 (MDR1), and thus, ABCB1 polymorphisms may influence the transport of methadone at the blood-brain barrier, affecting its adverse effects.

    OBJECTIVES: This study investigated the association between ABCB1 polymorphisms and cold pressor pain responses among opioid-dependent patients on methadone maintenance therapy (MMT).

    METHODS: Malay male opioid-dependent patients receiving MMT (n = 148) were recruited. Cold pressor pain responses (pain threshold, pain tolerance, and pain intensity) were measured at 0, 2, 4, 8, 12, and 24 hours post-methadone dose. DNA was extracted from whole blood and genotyped for ABCB1 polymorphisms including 1236C>T (rs1128503), 2677G>T/A (rs2032582), and 3435C>T (rs1045642) using the allelic discrimination real-time polymerase chain reaction. Repeated-measure analysis of variance between-group analysis was used to compare the three cold pressor pain responses and ABCB1 polymorphisms (1236C>T, 2677G>T/A, and 3435C>T) according to genotypes and allelic additive models, genotype dominant and recessive models, haplotypes, and diplotypes.

    RESULTS: Patients with 2677 GG or 2677G allele had the lowest pain threshold compared with 2677G>T/A genotypes or alleles (p = .007 and .002, respectively). Haplotype analysis showed a significant association between ABCB1 haplotypes and pain threshold (p = .02). Patients with 2677G allele had the lowest pain tolerance compared to those with 2677T and 2677A alleles (2677G < 2677T < 2677A allele carriers; p = .05). In terms of pain intensity scores, patients with 2677 GG or 2677G allele had the highest scores compared to other 2677G>T/A genotypes or alleles (p = .04 and .008, respectively). Haplotype analysis revealed a significant difference between patients with CGC haplotype and those without this haplotype (p = .02).

    DISCUSSION: To the best of our knowledge, this study provides the first evidence that ABCB1 polymorphisms are associated with cold pressor pain responses among Malay male patients with opioid dependence on MMT. The results may provide an initial prediction on heightened pain sensitivity or hyperalgesia for individuals who are carriers of the ABCB1 polymorphisms.
  14. AChE inhibitor: a regio- and stereo-selective 1,3-dipolar cycloaddition for the synthesis of novel substituted 5,6-dimethoxy spiro[5.3']-oxindole-spiro-[6.3″]-2,3-dihydro-1H-inden-1″-one-7-(substituted aryl)-tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole
    Ashraf Ali M, Ismail R, Choon TS, Kumar RS, Osman H, Arumugam N, et al.
    Bioorg Med Chem Lett, 2012 Jan 1;22(1):508-11.
    PMID: 22142546 DOI: 10.1016/j.bmcl.2011.10.087
    Pyrrolothiazolyloxindole analogues share vital pharmacological properties, considered useful in Alzheimer's disease (AD). The aim of this study was synthesis and evaluate pyralothiazolyloxindole analogues if possess acetyl cholinesterase (AChE) inhibitory activity. The easily accessible one-pot synthesis of these compounds resulted to be significantly less difficult and expensive than that of donepezil. Several compounds possess anti-cholinesterase activity in the order of micro and sub-micromolar. Particularly, compound was the most potent inhibitors of the series against acetyl cholinesterase enzyme with IC(50) 0.11μmol/L.
  15. Fulltext Acne fulminans with dapsone induced haemolysis: a case report
    Ismail R
    Med J Malaysia, 1987 Jun;42(2):124-6.
    PMID: 2971861
    Acne is one of the most common disorders affecting mankind. Although acne does not cause death, it however produces a lot of discomfort, disfigurement and psychological trauma, particularly in teenagers. Acne vulgaris is a chronic condition involving the pilosebaceous unit of the skin. It is characterised by the presence of comedones, inflammatory papules, pustules or cysts, and eventually by scarring. The end result of acne varies from hyperpigmentation, slight pitting, to extremely disfiguring scars that may develop into keloids. Acne fulminans is a rare disorder and is characterised by sudden explosive appearance of highly inflammatory, tender, crusted, ulcerated lesions involving the back, chest and face. It is one of the most scarring acute dermatologic disorders of young people. A case of acne fulminans in a young female who developed haemolysis due to dapsone is reported here.
  16. Fulltext Acrodermatitis continua of Hallopeau--a report of a case
    Ismail R, Chan SP
    Med J Malaysia, 1983 Sep;38(3):191-3.
    PMID: 6672560
  17. Fulltext Ambit determination method in estimating rice plant population density
    Abu Bakar, B., Abdul Rahman, M.S., Teoh, C.C., Abdullah, M.Z.K., Ismail, R.
    Food Research, 2018;2(2):177-182.
    MyJurnal
    Rice plant population density is a key indicator in determining the crop setting and fertilizer application rate. It is therefore essential that the population density is monitored to ensure that a correct crop management decision is taken. The conventional method of determining plant population is by manually counting the total number of rice plant tillers in a 25 cm x 25 cm square frame. Sampling is done by randomly choosing several different locations within a plot to perform tiller counting. This sampling method is time consuming, labour intensive and costly. An alternative fast estimating method was developed to overcome this issue. The method relies on measuring the outer circumference
    or ambit of the contained rice plants in a 25 cm x 25 cm square frame to determine the number of tillers within that square frame. Data samples of rice variety MR219 were collected from rice plots in the Muda granary area, Sungai Limau Dalam, Kedah. The data were taken at 50 days and 70 days after seeding (DAS). A total of 100 data samples were collected for each sampling day. A good correlation was obtained for the variety of 50 DAS and 70 DAS. The model was then verified by taking 100 samples with the latching strap for 50 DAS and 70 DAS. As a result, this technique can be used as a fast, economical and practical alternative to manual tiller counting. The technique can potentially be used in the development of an electronic sensing system to estimate paddy plant population density.
  18. An ecological study of the relationship between urban built environment and cardiovascular hospital admissions (2004-2016) in an Asian developing country
    Kwan SC, Ismail R, Ismail NH, Mohamed N
    Soc Sci Med, 2021 05;276:113868.
    PMID: 33799201 DOI: 10.1016/j.socscimed.2021.113868
    This study aims to evaluate the relationship between urban built environment and hospital admissions from cardiovascular diseases in Kuala Lumpur, Malaysia. Hospital admission data from 2004 to 2016 for cardiovascular diseases were used with patient residential postcodes as the unit of analysis. Data was split into 2004-2009 (12,551 cases) and 2010-2016 (17,154 cases) periods corresponding to land use data. We used generalized linear mixed model to analyse population density, property value, entropy index, and the kernel density (800 m) of specific land use, bus and rail stations, and road junctions, with time period and postcodes as the random effects to generate incidence rate ratios (IRRs). Results indicated that entropy index and recreational area density were associated with fewer hypertensive disease and ischemic heart disease hospital admissions (IRR range: 0.49-0.68, 95%CI: 0.27, 0.97). Population density and property value were associated with fewer cerebrovascular disease hospital admissions (IRR range: 0.29-0.34, 95%CI: 0.11, 0.75). Contrarily, density of road junctions was associated with 2.5-6.3 times more hospital admissions for cardiovascular disease hospital admissions (IRR range: 2.53-6.34, 95%CI: 1.07,17.91). There were no significant association between hospital admission and density of residential area, undeveloped land, rail and bus stations. The shapes of relationships for all attributes were non-linear, and changed markedly at the third quartile except for recreational area density. The findings suggest that land use attributes have some protective effects on the cardiovascular disease admission cases as compared to the transport attributes. These findings have important merits for integrating health into urban planning.
  19. An improved method for the preparations of nanostructured lipid carriers containing heat-sensitive bioactives
    Hung LC, Basri M, Tejo BA, Ismail R, Nang HL, Abu Hassan H, et al.
    Colloids Surf B Biointerfaces, 2011 Oct 1;87(1):180-6.
    PMID: 21652183 DOI: 10.1016/j.colsurfb.2011.05.019
    Heat-sensitive bioactive compounds such as β-carotene and tocols, are widely used in the pharmaceutical and cosmetic fields. Their chemical stability in delivery systems is one of the major concerns in the production of nanostructured lipid carriers (NLCs). A previously established high-temperature high-pressure homogenisation technique involved in the preparation of NLCs can cause degradation of heat-sensitive compounds. Therefore, a novel preparation process needs to be developed to minimise the degradation of heat-sensitive active compounds during the preparation of NLCs. In this work, modified methods A and B were designed to minimise the degradation of β-carotene and tocols during the production of NLCs. These methods improved the chemical stability of heat-sensitive bioactive compounds (β-carotene and tocols) significantly compared to the previously established method. The physical stability of the formulation was maintained throughout study duration.
  20. An improved rapid genotyping method for the study of beta-2 adrenergic receptor gene polymorphisms using single tube allele specific multiplex PCR
    Zilfalil BA, Hoh BP, Nizam MZ, Liza-Sharmini AT, Teh LK, Ismail R
    J Clin Pharm Ther, 2006 Dec;31(6):637-40.
    PMID: 17176369
    Seventeen single nucleotide polymorphisms (SNPs) have been identified so far, within the beta-2 receptor (beta(2) AR) gene. The presence of so many SNPs within the beta(2) AR gene causes a problem, for those studying beta(2) AR pharmacogenetics, in relation to which SNPs to choose. Most of the work has focused on the three common SNPs within the coding block (alleles 16, 27 and 164) and the techniques developed have been for these three functionally important alleles.
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