Displaying publications 1 - 20 of 30 in total

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  1. Fulltext Genetic polymorphisms of human platelet antigens-1 to -6, and -15 in the Malaysian population
    Tan JY, Lian LH, Nadarajan VS
    Blood Transfus, 2012 Jul;10(3):368-76.
    PMID: 22682339 DOI: 10.2450/2012.0095-11
    Human platelet antigens (HPA) are determinant in several platelet-specific alloimmune disorders, such as neonatal alloimmune thrombocytopenia, post-transfusion purpura and platelet transfusion refractoriness. The distribution of HPA systems in the Malaysian population is not known. Defining the patterns of HPA systems provides a basis for risk assessment and management of the above complications.
  2. Fulltext Angiotensin-converting enzyme gene I/D dimorphism does not play a major role in the susceptibility of Malaysian systemic lupus erythematosus patients
    Lian LH, Lau TP, Ching AS, Chua KH
    Genet. Mol. Res., 2012;11(2):863-71.
    PMID: 22576914 DOI: 10.4238/2012.April.10.2
    Systemic lupus erythematosus (SLE) is an autoimmune disease that causes systemic damage, involving auto-reactive antibodies and over-deposition of immune complexes. Susceptibility to SLE is believed to be multifactorial, and genetics is one of the proven etiological factors; it can affect SLE development, severity and prognosis. We investigated a possible association between the angiotensin-converting enzyme gene and susceptibility to SLE in the Malaysian population. PCR was employed for the determination of I/D dimorphism of this gene. The I allele was more frequent than the D allele in both the SLE patients (N = 170) and healthy controls (N = 190). However, there was no significant difference in the distribution of these two alleles between both groups studied (χ(2) = 0.284, P > 0.05). Interestingly, the DD homozygous genotype scored notably higher in the healthy control group (χ(2) = 7.568, P < 0.05), while the ID heterozygote was observed to be significantly associated with SLE (χ(2) = 11.143, P < 0.05). In conclusion, with respect to the Malaysian population, the DD genotype might play a protective role in the development of SLE while in contrast, those who carry the ID genotype might be at potential risk for onset of this disease.
  3. Genetic polymorphisms of EGF 5'-UTR and NAT2 857G/A associated with glioma in a case control study of Malaysian patients
    Muthusamy KA, Lian LH, Vairavan N, Chua KH, Waran V
    Genet. Mol. Res., 2012;11(3):2939-45.
    PMID: 22782629
    Studies of genetic mutations that have been used in predicting glioma prognosis have revealed a complex relationship between clinical and genetic factors. Epidermal growth factor (EGF) and the NAT2 gene play a central role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production, and the mutations in the NAT2 gene have been postulated as a risk factor for cancer. We investigated EGF and the NAT2 gene in 13 glioma tissue samples and 12 normal controls. In the EGF 5'-UTR 61G polymorphism, the heterozygote GA was the most common genotype in the glioma patients. In the NAT2 polymorphism at nucleotide position 857G/A, the G allele and the GG genotype were the most prevalent forms in both the glioma and normal samples. We did not find any homozygous AA genotypes in the glioma patients. Based on this preliminary evidence, the EGF 5'-UTR at position 61 and the NAT2 SNP at position 857 polymorphisms are associated with increased risk for glioma.
  4. Association of the functional polymorphism in the catechol-O-methyltransferase gene with schizophrenia in the three ethnic groups of the Malaysian population
    Wan CL, Zainal NZ, Lian LH, Mohamed Z
    Psychiatry Res, 2011 Aug 30;189(1):67-71.
    PMID: 21414668 DOI: 10.1016/j.psychres.2011.02.008
    The catechol-O-methyltransferase (COMT) gene is a candidate gene for schizophrenia as its encoded enzyme is involved in the metabolic inactivation of dopamine and noradrenaline. Several molecular genetic studies thus far have demonstrated that the COMT functional polymorphism of Val158Met is susceptible with schizophrenia. Hence, the present study aims to determine this genetic association of this SNP in the three major ethnic groups of the Malaysian population. A total of 317 patients (79 Malays, 154 Chinese and 84 Indians) meeting DSM-IV criteria for schizophrenia and 417 healthy subjects (160 Malays, 164 Chinese and 93 Indians) were recruited. A PCR-RFLP method was used to determine the genotypes and alleles present. We found a significant association of genotypes within the total pooled samples, as well as in the female subgroup, with a higher frequency of heterozygotes in schizophrenia subjects. However, there were no significant differences in allele and genotype frequency between the schizophrenic patients and normal controls in all three ethnic groups. Our current findings suggest that the Val158Met polymorphism has a weak association with schizophrenia in the Malaysian population and does not play a major role in conferring susceptibility to the schizophrenia in any of the three major local ethnicities.
  5. Fulltext Lack of association between RANTES-28, SDF-1 gene polymorphisms and systemic lupus erythematosus in the Malaysian population
    Lian LH, Kee BP, Ng HL, Chua KH
    Genet. Mol. Res., 2011;10(4):2841-50.
    PMID: 22095608 DOI: 10.4238/2011.November.17.2
    Regulated on activation, normal T-cell expressed and secreted (RANTES) and stromal cell-derived factor 1 (SDF-1) are members of the CC- and CXC-chemokine families, respectively. Both genes have been postulated to be involved in the pathogenesis of systemic lupus erythematosus (SLE). We analyzed position 28 of the RANTES gene promoter region, as well as the SNP observed in the 3' UTR of the SDF-1 gene at position 801, in 130 patients presenting SLE at the Malaya University Medical Centre. Screening of 130 healthy volunteer controls using RFLP was also performed. RANTES-28 polymorphism analysis showed no significant (P = 0.3520) relationship, even though homozygous C/C was more frequent in SLE patients (OR = 1.4183) and heterozygous C/G was more frequent in healthy controls (OR = 0.7051). There were no significant (P = 0.2650) associations between A/A (OR = 0.783), G/G (OR = 1.5914) and G/A (OR = 0.8289) genotypes in the SDF-1 gene polymorphism with SLE. We conclude that there is no significant association of RANTES-28 and SDF-1 gene polymorphisms and occurrence of SLE in Malaysia.
  6. Complement components 2 and 7 (C2 and C7) gene polymorphisms are not major risk factors for SLE susceptibility in the Malaysian population
    Lian LH, Ching AS, Chong ZY, Chua KH
    Rheumatol Int, 2012 Nov;32(11):3665-8.
    PMID: 21881993 DOI: 10.1007/s00296-011-2070-0
    There have been numerous studies linking complement components and the pathogenesis of systemic lupus erythematosus (SLE). This is due to their numerous roles in modulating immune responses in the human body. This study examined the association of C2 and C7 genetic polymorphisms with the susceptibility to SLE based on two separate cohorts of patient and control samples from Malaysia. The 28-bp deletion in the C2 exon-intron junction and single nucleotide polymorphism in the 3'untranslated region in the C7 genes were detected based on direct polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively. A total of 150 patient and 150 healthy control samples were screened, but there was no association detected between either genes. All individuals presented with null deletion in C2 genes, while the C allele and CC genotypes were most commonly scored. These overall results suggest a lack of strong association with the C2 and C7 gene polymorphisms to the susceptibility of SLE in the Malaysian population.
  7. Fulltext Interleukin-6 promoter polymorphisms (-174 G/C) in Malaysian patients with systemic lupus erythematosus
    Chua KH, Kee BP, Tan SY, Lian LH
    Braz. J. Med. Biol. Res., 2009 Jun;42(6):551-5.
    PMID: 19448905 DOI: 10.1590/s0100-879x2009000600012
    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves the inflammation of various organs upon deposition of immune complexes and is characterized by uncontrolled B cell hyperactivity. Despite intensive research on the etiology of the disease, the exact cause of the onset of SLE is unknown. The pathogenesis of the disease has been proposed to be associated with the imbalance of T helper type 1 (Th1) and Th2 cytokine activities. Elevated serum levels of interleukin-6 (IL-6), a Th2 cytokine with various functions in the regulation of human biological systems, are observed in SLE patients. In the present study, 100 Malaysian SLE patients and 100 controls were evaluated in order to determine the association of polymorphisms existing in the promoter region of the IL-6 gene with the onset of SLE. The homozygous G genotype was found to be significant in SLE patients (chi(2) = 33.754; P = 0.00000000625), whereas the heterozygous G/C genotype was significant in the controls (chi(2)= 25.087; P = 0.000000548). We suggest that the C allele might have a masking effect on the G allele when both alleles are present in heterozygous individuals. However, we did not observe any significant association of the homozygous C allele with the onset of SLE or with protection from the disease (chi(2) = 1.684; P = 0.194366).
  8. Antibiotic prophylaxis in elective colorectal surgery
    Gul YA, Lian LH, Jabar FM, Moissinac K
    ANZ J Surg, 2002 Apr;72(4):275-8.
    PMID: 11982514
    Antibiotics are often administered in elective colorectal surgery to prevent wound infection. The tendency for surgeons to prolong the administration of prophylactic antibiotic therapy in the postoperative period is a well-known fact. The aim of this study was to elucidate the pattern of prophylactic antibiotic utilization in elective colorectal surgery and to determine if evidence-based medicine is employed in relation to this practice.
  9. Population data of six Alu insertions in indigenous groups from Sabah, Malaysia
    Kee BP, Chua KH, Lee PC, Lian LH
    Ann Hum Biol, 2012 Nov-Dec;39(6):505-10.
    PMID: 22989108 DOI: 10.3109/03014460.2012.719548
    The present study is the first to report the genetic relatedness of indigenous populations of Sabah, Malaysia, using a set of Indel markers (HS4.32, TPA25, APO, PV92, B65 and HS3.23). The primary aim was to assess the genetic relationships among these populations and with populations from other parts of the world by examining the distribution of these markers.
  10. Fulltext Ethnic variation in interleukin-6 -174 (g/c) polymorphism in the malaysian population
    Gan GG, Subramaniam R, Lian LH, Nadarajan V
    Balkan J Med Genet, 2013 Dec;16(2):53-8.
    PMID: 24778564 DOI: 10.2478/bjmg-2013-0032
    Interleukin-6 (IL-6) is one of the cytokines that has been well studied and implicated in many diseases including cancers. The frequency of the IL-6 -174 (G/C) polymorphism had been proven to differ in various populations. Malaysia is a country with three major ethnic populations, Malays, Chinese and Indians. In this study, we proposed to determine the G or C allele frequency of the IL-6 -174 polymorphism in these three populations. A total of 348 blood samples were available for analysis. The median age for the subjects was 31 years. There were a total of 245 males and 103 females. A total of 86 Malays (25.0%), 122 Chinese (33.0%) and 140 Indians (40.0%) were genotyped. The result showed a significant difference in the G or C allele frequency of the -174 polymorphism. The total frequencies for the G and C alleles were 91.0 and 9.0%, respectively. In the Malays, the allele frequency of the C allele was 4.0% compared with 19.0% in the Indians. The C allele was not detected in the Chinese population. This finding is the first reported on the Malaysian population and may be important in determining risk of diseases associated with the IL-6 polymorphism in these three populations.
  11. Association between genetic polymorphisms in interferon regulatory factor 5 (IRF5) gene and Malaysian patients with Crohn's disease
    Chua KH, Lian LH, Khor WC, Lee WS, Hilmi I, Goh KL, et al.
    J Dig Dis, 2015 Apr;16(4):205-16.
    PMID: 25564941 DOI: 10.1111/1751-2980.12229
    The study aimed to investigate the association between the interferon regulatory factor 5 (IRF5) gene polymorphisms and the onset of Crohn's disease (CD) in a Malaysian cohort.
  12. Fulltext Association between EGF and VEGF functional polymorphisms and sporadic colorectal cancer in the Malaysian population
    Lau TP, Roslani AC, Lian LH, Lee PC, Hilmi I, Goh KL, et al.
    Genet. Mol. Res., 2014;13(3):5555-61.
    PMID: 25117311 DOI: 10.4238/2014.July.25.9
    Growth factors are polypeptides that are critical for the initiation, progression, and metastasis of cancer. Most tumor cells are capable of synthesizing particular growth factors leading to constitutive pathway activation in these cells through autocrine signaling. Epidermal growth factor (EGF) is a potent mitogenic peptide that exerts direct effects on the proliferation and differentiation of tumor cells in carcinogenesis. By contrast, vascular endothelial growth factor (VEGF) is vital for the invasion and metastasis of neoplasms through the formation of new blood vessels from mature endothelial cells. In this study, we investigated the association between functional polymorphisms of both the EGF and VEGF genes and colorectal cancer (CRC) susceptibility. A total of 130 CRC patients and 212 healthy controls were recruited for this case-control study. Genotyping of genetic variants was conducted via real-time polymerase chain reaction (PCR) amplification with allele-specific TaqMan probes. None of the genotypes of the EGF +61 A>G and VEGF +936 C>T variants was significantly associated with CRC susceptibility among the Malaysian subjects evaluated (P > 0.05). The observed frequency distributions of the EGF +61 A>G polymorphism genotypes showed ethnic heterogeneity, which was not the case for the VEGF +936 C>T genotypes. In conclusion, no positive correlation between these functional polymorphisms and CRC risk was found in this Malaysian population. Studies of the EGF and VEGF genes and CRC susceptibility are scarce, and the results reported thus far differ from one population to another. Hence, more replication studies are warranted before any firm conclusions can be made.
  13. Fulltext Evaluation of SLE susceptibility genes in Malaysians
    Molineros JE, Chua KH, Sun C, Lian LH, Motghare P, Kim-Howard X, et al.
    Autoimmune Dis, 2014;2014:305436.
    PMID: 24696779 DOI: 10.1155/2014/305436
    Systemic Lupus Erythematosus (SLE) is a clinically heterogeneous autoimmune disease with strong genetic and environmental components. Our objective was to replicate 25 recently identified SLE susceptibility genes in two distinct populations (Chinese (CH) and Malays (MA)) from Malaysia. We genotyped 347 SLE cases and 356 controls (CH and MA) using the ImmunoChip array and performed an admixture corrected case-control association analysis. Associated genes were grouped into five immune-related pathways. While CH were largely homogenous, MA had three ancestry components (average 82.3% Asian, 14.5% European, and 3.2% African). Ancestry proportions were significantly different between cases and controls in MA. We identified 22 genes with at least one associated SNP (P < 0.05). The strongest signal was at HLA-DRA (P Meta = 9.96 × 10(-9); P CH = 6.57 × 10(-8), P MA = 6.73 × 10(-3)); the strongest non-HLA signal occurred at STAT4 (P Meta = 1.67 × 10(-7); P CH = 2.88 × 10(-6), P MA = 2.99 × 10(-3)). Most of these genes were associated with B- and T-cell function and signaling pathways. Our exploratory study using high-density fine-mapping suggests that most of the established SLE genes are also associated in the major ethnicities of Malaysia. However, these novel SNPs showed stronger association in these Asian populations than with the SNPs reported in previous studies.
  14. Fulltext NOD2/CARD15 variants in Malaysian patients with sporadic colorectal cancer
    Lau TP, Roslani AC, Lian LH, Lee PC, Hilmi I, Goh KL, et al.
    Genet. Mol. Res., 2014;13(3):7079-85.
    PMID: 24682985 DOI: 10.4238/2014.March.19.3
    Colorectal cancer (CRC) is one of the most common types of cancer in both developed and developing countries. This disease is triggered by and progresses via the sequential accumulation of multiple genetic alterations. In addition, the interaction between low-penetrance genes and environmental factors can also increase the risk of developing CRC. Since inflammatory bowel diseases (IBDs) are one of the predisposing factors for CRC, IBD-related genes might, to a certain extent, be associated with cancer initiation. The nucleotide oligomerization domain 2/caspase activating recruitment domain 15 gene (NOD2/CARD15) is the most well-established gene to be associated with increased susceptibility to Crohn's disease. Thus, various studies have been performed to investigate the potential contribution of this gene to CRC risk. In this study, we aimed to determine the frequency of the Arg702Trp, Gly908Arg, 3020insC, Pro268Ser, and JW1 variants of NOD2/CARD15, and to investigate their association with CRC susceptibility. A total of 130 CRC patients and 212 healthy controls were recruited for this study. Subsequently, real-time polymerase chain reaction with TaqMan was performed for the genotyping of these NOD2/ CARD15 variants. None of the NOD2/CARD15 variants was statistically associated to CRC susceptibility in our Malaysian population. Our findings were remarkably similar to those of other Asian cohorts, which indicated that these NOD2/CARD15 variants exhibit genetic heterogeneity between Caucasian and Asian populations.
  15. Association between inflammatory bowel disease gene 5 (IBD5) and interleukin-23 receptor (IL23R) genetic polymorphisms in Malaysian patients with Crohn's disease
    Chua KH, Hilmi I, Lian LH, Patmanathan SN, Hoe SZ, Lee WS, et al.
    J Dig Dis, 2012 Sep;13(9):459-65.
    PMID: 22908971 DOI: 10.1111/j.1751-2980.2012.00617.x
    This study was aimed to investigate the possible association of Crohn's disease (CD) with inflammatory bowel disease gene 5 (IBD5) IGR2198a_1 (rs11739135), IGR2096a_1 (rs12521868) and interleukin-23 receptor (IL23R) genetic variant (rs1004819) in the Malaysian population.
  16. Fulltext Genetic data for 15 STR loci in a Kadazan-Dusun population from East Malaysia
    Kee BP, Lian LH, Lee PC, Lai TX, Chua KH
    Genet. Mol. Res., 2011;10(2):739-43.
    PMID: 21523653 DOI: 10.4238/vol10-2gmr1064
    Allele frequencies of 15 short tandem repeat (STR) loci, namely D5S818, D7S820, D13S317, D16S539, TH01, TPOX, Penta D, Penta E, D3S1358, D8S1179, D18S51, D21S11, CSF1PO, vWA, and FGA, were determined for 154 individuals from the Kadazan-Dusun tribe, an indigenous population of East Malaysia. All loci were amplified by polymerase chain reaction, using the Powerplex 16 system. Alleles were typed using a gene analyzer and the Genemapper ID software. Various statistical parameters were calculated and the combined power of discrimination for the 15 loci in the population was calculated as 0.999999999999999. These loci are thus, informative and can be used effectively in forensic and genetic studies of this indigenous population.
  17. Identification of DLG5 and SLC22A5 gene polymorphisms in Malaysian patients with Crohn's disease
    Chua KH, Lian LH, Kee BP, Thum CM, Lee WS, Hilmi I, et al.
    J Dig Dis, 2011 Dec;12(6):459-66.
    PMID: 22118696 DOI: 10.1111/j.1751-2980.2011.00533.x
    The aim of this study was to investigate the association of DLG5 and SLC22A5 gene polymorphisms with the onset of Crohn's disease (CD) in a Malaysian cohort.
  18. A study of association of the complement C4 mutations with systemic lupus erythematosus in the Malaysian population
    Puah SM, Lian LH, Chew CH, Chua KH, Tan SY
    Lupus, 2007;16(9):750-4.
    PMID: 17728371 DOI: 10.1177/0961203307079454
    The aim of the present study was to investigate the association of C4 gene mutations with systemic lupus erythematosus, in 130 Malaysian SLE patients and 130 healthy controls. Generally, various PCR approaches were used to screen the mutations of the C4 genes, which included 2 bp (+TC) insertions at codon 1213 in exon 29, 1 bp deletions (-C) at codon 811 in exon 20, 1 bp (-C), 2 bp (-GT) deletions at codons 522 and 497 in exon 13 and null alleles. No mutations located at exons 13, 20 and 29 of the C4 gene, were detected amongst the patient and control samples in this study. C4A*Q0 was found in two out of the 130 control samples, while C4B*Q0 was present in two out of the 130 SLE patients. Overall, our results do not demonstrate a significant association to these known C4 mutations identified by previous studies, in the Malaysian scenario.
  19. A simple instrument for the assessment of student performance in problem-based learning tutorials
    Sim SM, Azila NM, Lian LH, Tan CP, Tan NH
    Ann Acad Med Singap, 2006 Sep;35(9):634-41.
    PMID: 17051280
    INTRODUCTION: A process-oriented instrument was developed for the summative assessment of student performance during problem-based learning (PBL) tutorials. This study evaluated (1) the acceptability of the instrument by tutors and (2) the consistency of assessment scores by different raters.

    MATERIALS AND METHODS: A survey of the tutors who had used the instrument was conducted to determine whether the assessment instrument or form was user-friendly. The 4 competencies assessed, using a 5-point rating scale, were (1) participation and communication skills, (2) cooperation or team-building skills, (3) comprehension or reasoning skills and (4) knowledge or information-gathering skills. Tutors were given a set of criteria guidelines for scoring the students' performance in these 4 competencies. Tutors were not attached to a particular PBL group, but took turns to facilitate different groups on different case or problem discussions. Assessment scores for one cohort of undergraduate medical students in their respective PBL groups in Year I (2003/2004) and Year II (2004/2005) were analysed. The consistency of scores was analysed using intraclass correlation.

    RESULTS: The majority of the tutors surveyed expressed no difficulty in using the instrument and agreed that it helped them assess the students fairly. Analysis of the scores obtained for the above cohort indicated that the different raters were relatively consistent in their assessment of student performance, despite a small number consistently showing either "strict" or "indiscriminate" rating practice.

    CONCLUSION: The instrument designed for the assessment of student performance in the PBL tutorial classroom setting is user-friendly and is reliable when used judiciously with the criteria guidelines provided.

  20. Fulltext Lack of association between TYK2 and STAT3 genes and Crohn's disease in the Malaysian population
    Lian LH, Lau TP, Lee VL, Lee WS, Hilmi I, Goh KL, et al.
    Genet. Mol. Res., 2013;12(1):167-74.
    PMID: 23408403 DOI: 10.4238/2013.January.24.9
    This study aimed to investigate the potential association of TYK2 and STAT3 genes with the susceptibility to Crohn's disease (CD) among Malaysians. DNA samples were obtained from 80 CD patients and 100 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism methods were employed for genotyping, followed by statistical analysis. In our current study, none of the single nucleotide polymorphisms of either TYK2 or STAT3 was statistically associated with the susceptibility to CD in our local population (P > 0.05). In contrast, there was a statistically significant association between the G/G homozygotes of the STAT3 rs2293152 and the healthy control group (χ(2) = 6.229, P < 0.05). In conclusion, our study does not support the role of the TYK2 and STAT3 genes influencing CD susceptibility.
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