Effects of leptin gene variants on obesity and its attributes in Malay population

Leptin is a hormone that regulates the energy intake and expenditure which is encoded by leptin gene. Leptin gene variants were studied comprehensively in relation with body weight status, but the evidences were indecisive. This study was to determine the association between leptin gene variants, G2548A, H1328080 and A19G with obesity and its attributes in Terengganu, Malaysian population. This study involved a total of 249 Malay subjects (101 healthy adults with normal BMI as the control group and 148 overweight and obese subjects). The anthropometrics data were obtained, blood samples were collected for genetic markers and lipid profile analyses. PCR-RFLP technique was performed to determine the genotype and allele distribution of leptin gene variants. The genotypic and allelic frequencies of leptin gene variants presented no significant difference between groups, G2548A (P = 0.93 and 0.74); H1328080 (P = 0.58 and 0.56); and A19G (P = 0.72 and 0.38) correspondingly. However, there was statistical significant difference between triglyceride level and genotypes of G2548A variant (P = 0.016); between total cholesterol level and H1328080 genotypes (P = 0.027). In addition, multivariate logistic regression projected the male gender (adjusted OR= 26.27; CI= 1.06-1.25; P = 0.009), waist circumference (adjusted OR = 1.15; CI = 1.06-1.25; P = 0.001) and body fat percentage (adjusted OR = 1.43; CI = 1.20-1.70; P<0.001) were the independent risk factors for obesity. The data suggest G2548A, H1328080 and A19G variants were not associated with obesity. However, waist circumference and body fat percentage may increase risk for obesity in Malay population

Korelasi antara Projek Genom Melayu dengan akidah Islam

Projek Genom Melayu (PGM) merupakan penyelidikan berkaitan genom bangsa Melayu yang dipelopori oleh dua buah Universiti Awam (UA) di Malaysia iaitu Universiti Teknologi MARA (UiTM) dan Universiti Sains Malaysia (USM) yang menfokuskan penghasilan produk farmaseutikal dan mengenal pasti asal-usul bangsa Melayu itu sendiri. Walaupun ia sangat bermanfaat kepada masyarakat Melayu, penyelidikan ini masih terikat dengan etika sains dan nilai-nilai kemanusiaan berkaitan perundangan dan keagamaan. Oleh itu, kajian ini bertujuan menghuraikan kerangka teori kajian dan mengenal pasti hubungan antara PGM dengan akidah Islam seterusnya mencadangkan Indeks Pematuhan Akidah Islam (IPAI) terhadap PGM sebagai tapisan kedua selapas etika sains. Kajian ini menggunakan pendekatan kualitatif dan kuantitatif yang dikenali sebagai Kaedah Campuran Penerokaan Berturutan (Exploratory Sequencial Mixed Method) terhadap literatur utama dalam bidang berkaitan menggunakan analisis kandungan dan soal selidik terhadap ahli akademik UA di Malaysia menggunakan perisian IBM SPSS 21.0. Kajian ini mendedahkan bahawa terdapat hubungan yang positif antara pembolehubah-pembolehubah kajian (p-value < 0.05) iaitu PGM dengan akidah Islam (0.403), akidah Islam dengan IPAI (0.639) dan PGM dengan IPAI (0.304). Oleh yang demikian, integrasi antara PGM dengan akidah Islam mampu menghasilkan penyelidikan saintifik yang selari dengan ajaran Islam di samping memberi nilai tambah terhadap korpus ilmu pengetahuan semasa

Study of association of TGF-ß1 polymorphism with breast density in a tertiary medical center of Malaysia

Early detection of breast cancer risk by screening tools such as mammography can reduces the cost of treatment management and the prognosis of the disease. The level of breast density of in mammogram is one of the potential cofounder factor for breast cancer risk. The development of mammary epithelial cells is determined by the genetic factor. Transforming growth factor-beta (TGF-ß) gene involves in the regulation of cell proliferation and cell division. This study aimed to assess the association of TGF-ß1 polymorphisms with breast density among women who underwent breast screening using mammogram. The detection of genotypes for three polymorphisms of TGF-ß1 assigned as rs1800469, rs1800470 and rs4803455 were performed using PCR-RFLP technique. The allele and genotype frequencies were calculated for control group that consists of BIRADS 1 and BIRADS 2 class whilst case group consisted of BIRADS 3 and BIRADS 4 class. Two polymorphisms (rs1800469 and rs1800470) yielded a significant association with breast density with p value of 0.004 and 0.003, respectively. However, the third polymorphism, rs4803455 did not yield a significant association (p value=0.090). Haplotype association analysis might suggest the haplotype GAA conferred susceptibility (p value= 0.02, OR=2.21[1.07-4.55]) rather than haplotype AAC predispose a protective effect (p value=0.004, OR=0.40[0.21-0.77]) to breast density development. This preliminary data on single and haplotype association might reveal the association of polymorphisms of TGF-ß1 with breast density and give an insight on the role of polymorphism in predisposing to breast density development

Gene Expression Profiling and Protein Analysis Reveal Suppression of the C-Myc Oncogene and Inhibition JAK/STAT and PI3K/AKT/mTOR Signaling by Thymoquinone in Acute Myeloid Leukemia Cells

Overexpression of c-Myc plays an essential role in leukemogenesis and drug resistance, making c-Myc an attractive target for cancer therapy. However, targeting c-Myc directly is impossible, and c-Myc upstream regulator pathways could be targeted instead. This study investigated the effects of thymoquinone (TQ), a bioactive constituent in Nigella sativa, on the activation of upstream regulators of c-Myc: the JAK/STAT and PI3K/AKT/mTOR pathways in HL60 leukemia cells. Nextgeneration sequencing (NGS) was performed for gene expression profiling after TQ treatment. The expression of c-Myc and genes involved in JAK/STAT and PI3K/AKT/mTOR were validated by quantitative reverse transcription PCR (RT-qPCR). In addition, Jess assay analysis was performed to determine TQ’s effects on JAK/STAT and PI3K/AKT signaling and c-Myc protein expression. The results showed 114 significant differentially expressed genes after TQ treatment (p < 0.002). DAVID analysis revealed that most of these genes’ effect was on apoptosis and proliferation. There was downregulation of c-Myc, PI3K, AKT, mTOR, JAK2, STAT3, STAT5a, and STAT5b. Protein analysis showed that TQ also inhibited JAK/STAT and PI3K/AKT signaling, resulting in inhibition of c-Myc protein expression. In conclusion, the findings suggest that TQ potentially inhibits proliferation and induces apoptosis in HL60 leukemia cells by downregulation of c-Myc expression through inhibition of the JAK/STAT and PI3K/AKT signaling pathways

Sequence polymorphism and haplogroup data of the hypervariable regions on mtDNA in Semoq Beri population

Orang Asli is the aboriginal people in Peninsular Malaysia who have been recognized as indigenous to the country and still practicing traditional lifestyle. The molecular interest on the Orang Asli started when the earliest prehistoric migration occurred approximately 200 kya and entering Peninsular Malaysia 50 kya in stages. A total of three groups of Orang Asli present in Peninsular Malaysia, namely, Negrito also known as Semang, Senoi and Proto Malays. Through records, there is no research has been conducted on mtDNA variations in the Semoq Beri population, one of the tribes in Senoi group. In this report, variations of mtDNA were analysed in the population in Hulu Terengganu as an initial effort to establish the genetic characterisation and elucidating the history of Orang Asli expansion in Peninsular Malaysia. An array of mtDNA parameters was estimated and the observed polymorphisms with their respective haplogroups in comparison to rCRS were inferred respectively. The DNA sequences are registered in the NCBI with accession numbers KY853670-KY853753

Isu-Isu Genetik Manusia Dari Perspektif Sains & Islam

Kejuruteraan genetik dan teknologi rekombinan merupakan penemuan penting yang telah memacu perkembangan pesat dalam bidang bioteknologi moden terutamanya dalam penyelidikan dan pembangunan (R&D). Walaupun begitu, perkembangan tersebut menimbulkan isu dan persoalan agama serta etika khususnya melibatkan teknik pembiakan buatan, pemindahan organ, pengklonan dan kejuruteraan genetik itu sendiri. Isu etika sering ditekankan dalam pelbagai cabang ilmu dan memainkan peranan sangat penting dalam sistem hidup manusia serta berkait rapat dengan agama. Oleh yang demikian, penulisan kertas kerja ini bertujuan mendedahkan berkaitan Projek Genom Manusia (PGM) dan isu-isu genetik manusia yang timbul dari perspektif sains dan Islam seperti Teori Evolusi Darwin, PGM, pengklonan manusia dan eugenik. Akhirnya, isu-isu yang timbul dari aplikasi teknologi genetik manusia perlu ditangani dengan sebaik mungkin melalui etika sains serta diintegrasikan dengan ajaran Islam supaya segala pencapaian bidang ini tidak merosakkan alam dan populasi manusia seterusnya menjadikan kehidupan manusia lebih baik dan kondusif dari semasa ke semasa

Application of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique in the analysis of MYO1H single nucleotide polymorphism in Malay mandibular prognathism patients

Genetic studies have reported the association between polymorphism in MYO1H with mandibular prognathism. MYO1H is found in skeletal muscle sarcomeres and is expressed in the mandibular jaw cartilage signifying its importance during craniofacial development. This study aimed to characterise the genotype and allele of MYO1H single nucleotide polymorphism (SNP) (rs3825393) and to associate the SNP with mandibular prognathism in Class III skeletal malocclusion. This was a case-control study, which involved 57 Malay subjects with 30 Class I (control) and 27 Class III skeletal base patients (case). Cephalometric measurements were taken prior to collection of saliva samples. MYO1H SNP (rs3825383) was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chi-square (χ2) test was used to compare genotype and allele frequencies between the groups while Hardy-Weinberg Equilibrium (HWE) was applied to assess distribution of genotype frequency in both classes. MYO1H SNP (rs3825393) did not yield significant association with mandibular prognathism with p = 0.33; OR = 0.66; 95% CI = 0.289~1.518, that was reflected by no significant difference in allele (p > 0.05) and genotype (p > 0.05) frequency between control and study group. Nevertheless, AA genotype depicted the highest frequency in both groups. The genotype distribution in both groups was in concordance with HWE (p > 0.05). Our data showed no association of MYO1H SNP (rs3825393) with mandibular prognathism. Interestingly, we observed Allele A representing the major allele in Malay population. Presence of MYO1H SNP (rs3825393) was detected in samples analysed. Larger number of samples is required to confirm the involvement of MYO1H polymorphisms in mandibular prognathism

Disrupted-in-schizophrenia-1 SNPs and susceptibility to schizophrenia: evidence from Malaysia

Even though the role of the DICS1 gene as a risk factor for schizophrenia is still unclear, there is substantial evidence from functional and cell biology studies that supports the connection of the gene with schizophrenia. The studies associating the DISC1 gene with schizophrenia in Asian populations are limited to East-Asian populations. Our study examined several DISC1 markers of schizophrenia that were identified in the Caucasian and East-Asian populations in Malaysia and assessed the role of rs2509382, which is located at 11q14.3, the mutual translocation region of the famous DISC1 translocation [t (1; 11) (p42.1; q14.3)]. METHODS: We genotyped eleven single-neucleotide polymorphism (SNPs) within or related to DISC1 (rs821597, rs821616, rs4658971, rs1538979, rs843979, rs2812385, rs1407599, rs4658890, and rs2509382) using the PCR-RFLP methods. RESULTS: In all, there were 575 participants (225 schizophrenic patients and 350 healthy controls) of either Malay or Chinese ethnicity. The case-control analyses found two SNPs that were associated with schizophrenia [rs4658971 (p=0.030; OR=1.43 (1.35-1.99) and rs1538979-(p=0.036; OR=1.35 (1.02-1.80)] and rs2509382-susceptibility among the males schizophrenics [p=0.0082; OR=2.16 (1.22-3.81)]. This is similar to the meta-analysis findings for the Caucasian populations. CONCLUSION: The study supports the notion that the DISC1 gene is a marker of schizophrenia susceptibility and that rs2509382 in the mutual DISC1 translocation region is a susceptibility marker for schizophrenia among males in Malaysia. However, the finding of the study is limited due to possible genetic stratification and the small sample size. KEYWORDS: DISC1; SNPs; Schizophrenia; Susceptibilit

Identification of RS9960767 at TCF4 gene in Malaysian schizophrenia and rheumatoid arhtritis patients: a preliminary study

Objectives: Mutation of a TCF4 gene was previously reported as the cause of Schizophrenia. As documented long ago, there were inverse relationship between Schizophrenia (SZ) and Rheumatoid Arthritis (RA). Aim of this study is to detect genetic associations of a Single Nucleotide Polymorphism (SNP), rs9960767 at TCF4 gene between both patients group with controls. Methods: A total of 3ml whole blood was obtained from 47 SZ patients, 47 RA patients and 48 controls. Genomic DNA was extracted and PCR amplification of the exon 18 of TCF4 gene was performed. The PCR amplicon was digested with AluI restriction enzyme for rapid genotyping of the SNP and followed with 3% gel electrophoresis. Single association was analyzed using online SHEsis software based on Hardy-Weinberg Equilibrium using Chi-square calculation with 95% confidence interval (CI) and P value <0.05 is considered statistically significant. Results: The incidence of the mutation allele among the patients were 3.2% in SZ and 2.1% in RA while compared to controls incidence are 3.1% (p=0.98, OR=0.978; %95 CI=0.193-4.98 between SZ and controls and p=0.67, OR=1.48; %95 CI=0.24-9.09 between RA and controls). Genotype frequencies for SZ, RA and controls for AA (wild type homozygous) are 93.6 %, 97.9% and 93.8% respectively. AC genotype frequencies (mutant heterozygous) are 6.4% for SZ, 4.3% for RA and 6.2% for controls. However, none was found for allele CC (mutant homozygous) in all groups. Conclusion: The presence of SNP rs9960767 of the TCF4 gene statistically did not show association in our SZ patients. The negative association arises when the C allele from the SNP predispose to RA and protects from having SZ. However, a bigger sample size is needed to confirm this correlation

The cytotoxicity effect and identification of bioactive compounds of Prismatomeris glabra crude leaf extracts against breast cancer cells

Abstract Background Despite the fact that natives of Southeast Asia have been consuming Prismatomeris glabra for decades for a variety of health benefits, research on this species is not as extensive as that on other species due to its limited distribution. The purpose of this study was to determine the cytotoxicity and identify the bioactive compounds of P. glabra crude leaf extracts against the MCF-7 cell line. Results We first examined the potential cytotoxic activity of P. glabra using the MTT assay against the MCF-7 cell line to determine the IC50 of the plant extracts at various concentrations at three time points (24 h, 48 h, and 72 h). Across all time points, the MTT assay revealed that the aqueous extract exhibited the lowest IC50 values (p < 0.05) compared to the ethanol and methanol extracts. All plant extracts exerted the ability to induce cell death in the MCF-7 cell line at all time points, and the optimal time for P. glabra to manifest its antiproliferative activities and promote cell death was 48 h. LC–MS analysis was conducted to reveal the components in plant extracts. Forty compounds were discovered in P. glabra's extracts, with the majority being flavonoids and triterpenoids. Five similar compounds were present in all three extracts. Further research should be conducted on these compounds to unveil a compound that fulfils the criteria as a promising anticancer agent. This research is of the utmost importance, as it provides a fundamental framework for the identification of alternative therapies for breast cancer and contributes implicitly to the development of new drugs. Conclusions This study discovered that P. glabra crude leaf extracts have the potential to inhibit the MCF-7 cell line by inducing cell death