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

Preliminary study of PAX9 single nucleotide polymorphism (rs8004560) in patients with Class II skeletal base malocclusion contributed by mandibular retrognatism

Polymorphism in PAX9 (rs8004560), a gene responsible for craniofacial and tooth development, is often associated with Class II/Div2 malocclusion. This study aimed to detect the presence of PAX9 SNP (rs8004560) and to determine its genotype and allele distribution in Class II skeletal base malocclusion, contributed by retrognathic mandible, in the local Malaysian population. The association of PAX9 SNP (rs8004560) with Class II skeletal base malocclusion was also determined. A case control study was performed on 30 samples; 15 from Class II skeletal base malocclusion, and 15 from Class I skeletal base subject as control. Cephalometric measurements were performed prior to saliva samples collection. Genomic DNA was extracted from unstimulated saliva of all subjects, and the DNA was amplified using specific primers for marker rs8004560, followed by genotyping by sequencing. SHEsis online software was used to analyse Hardy-Weinberg Equilibrium (HWE) for cases and controls. Allelic and genotypic frequencies were compared between cases and controls. Significant difference in allele frequency was observed within the group whereby G allele was over-represented in the analysed population (p<0.05). However, when compared between cases and control; there was no significant association between PAX9 SNP (rs8004560) with Class II skeletal base malocclusion (p=0.56, OR=0.71; 95% CI=0.225-2.246). The distribution of genotype frequency in both groups were consistent with HWE (p>0.05). Although no genetic association between PAX9 SNP (rs8004560) with Class II skeletal base malocclusion was observed, significant difference in allele frequency observed might provide some indication in the involvement of PAX9 polymorphism in Class II skeletal base malocclusion contributed by retrognathic mandible. Further research utilising larger sample size will be required in order to determine the role of PAX9 gene in the aetiology of Class II skeletal base malocclusion observed in the local Malaysian population

Thymoquinone Suppresses Cell Proliferation and Enhances Apoptosis of HL60 Leukemia Cells through Re-Expression of JAK/STAT Negative Regulators.

The natural compound, thymoquinone (TQ) has demonstrated potential anticancer properties in inhibiting cell proliferation and promoting apoptosis in myeloid leukemia cells, breast cancer cells, and others. However, the effect mechanism of TQ on AML cells still not fully understood. In this study, the authors examined the effects of TQ on the expression of JAK/STAT-negative regulator genes SOCS-1, SOCS-3, and SHP-1, and their consequences on cell proliferation and apoptosis in HL60 leukemia cells. MTT and trypan blue exclusion tests were conducted to determine the 50% inhibitory concentration (IC50) and cell proliferation. FITC Annexin and Guava® reagent were used to study the cell apoptosis and examine the cell cycle phases, respectively. The expression of JAK/STAT-negative regulator genes, SOCS-1, SOCS-3, and SHP-1, was investigated using reverse transcriptase- quantitative PCR (RT-qPCR). TQ demonstrated a potential inhibition of HL60 cell proliferation and a significant increase in apoptotic cells in dose and time-dependent manner. TQ significantly induced cycle arrest at G0-G1 phase (P .This work was funded by the Fundamental Research Grant Scheme of the Ministry of Education, Malaysia [FRGS/1/2019/SKK08/UNISZA/02/3 (RR330)]