1.Influence of CYP2D6 polymorphisms on symptomatology and side effects of patients with schizophrenia in Malaysia
Zalina Zahari ; Mohd Razali Salleh ; Lay Kek Teh ; Rusli Ismail
Malaysian Journal of Medical Sciences 2009;16(3):13-22
Background: Our objective was to investigate the association of CYP2D6 polymorphisms with
symptoms and side-effects of patients with schizophrenia.
Methods: The subjects were 156 patients with schizophrenia undergoing antipsychotic treatment
at a psychiatric clinic. Patients with co-morbid diagnoses of substance abuse or mental retardation were
excluded from the study. Psychopathology was evaluated using the Positive and Negative Symptoms
Scale (PANSS). Extrapyramidal side-effects and akathisia were assessed with the Simpson Angus Scale
(SAS) and the Barnes Akathisia Rating Scale (BARS), respectively. DNA was extracted from blood and
subjected to PCR-genotyping.
Results: We found that CYP2D6 polymorphisms were significantly associated with a subtotal
negative PANSS score. In addition, CYP2D6 is not related to side-effects of antipsychotic therapy, or
SAS and BARS scores. The results suggest that CYP2D6 polymorphisms may have implications in
treatment response.
Conclusions: Therefore, CYP2D6 may be a predictor for treatment outcomes of patients with
schizophrenia. However, further investigation is required to confirm these findings in a larger sample.
2.Technology Advancement Enabling the Link of Gut Microbiota with Obesity and Metabolic Disorder
Hartini Yusof ; Mohamad Shafiq Aazmi ; Ili Ng Abdullah ; Teh Lay Kek ; Aminuddin Ahmad ; Mazlifah Omar ; Thuhairah Rahman ; Mohd Zaki Salleh
Malaysian Journal of Health Sciences 2015;13(1):77-91
Obesity is a growing epidemic due to an accelerated phase of industrialization and urbanization with the overfed people
now outnumbered the underfed. It is the major public health problem with a lot of research interest as it is associated
with many complicated chronic disorders such as type-2 diabetes, cardiovascular diseases (CVD) and cancers. A global
estimation of 2.8 million deaths per year is due to obesity and there are tremendous on-going efforts to identify hosts
and environmental factors that infl uence the cause and pathogenesis of obesity. Concerted efforts from different research
groups had successfully shown that obese subjects have altered composition of gut microbiota and transplantation of this
microbiota infl uences body weight in the germ-free recipient mice. The advancement of technology had made possible
the study of gut microbiota which was unculturable for better understanding of their impact to human health. Rapid
deep sequencing of DNA at reasonable cost through various options of platforms followed by data analysis using robust
bioinformatic tools are an important way of analysing the gut microbiome. Here we review the role of gut microbiota
which modulates host’s metabolic functions and gene expression, facilitating the extraction and storage of energy from the
ingested dietary substances and leading to body-weight gain. We will discuss on the different techniques used, focusing
on the high-defi nition technologies for the determination of the composition, function and ecology of gut microbiota. This
allows the appropriate selection of platform which becomes the key for success of subsequent research.
Obesity
3.Peri-implant Bone Healing: Its Basic Osteogenesis and Biomarkers
Muhammad Amal Abd Wahab ; Eleena Mohd Yusof ; Rohana Ahmad ; Mohd Zaki Salleh ; Teh Lay Kek
Malaysian Journal of Medicine and Health Sciences 2022;18(No.6):324-331
The continuous sequence of bone healing phases starts off with osteoconduction to the implant surface, depending on the migration of osteogenic cells. Osteoneogenesis ensues resulting in a mineralised interfacial matrix and
is followed by bone remodelling to the implant interface at discrete sites. Dental implant drilling procedure and
placement produce osseous defect which is filled by blood. Within seconds, blood proteins are adsorbed onto the
implant surface and platelets are activated resulting in the release of cytokines and growth factors. Further platelet
aggregation initiates osteoconduction to the surface, followed by osteoneogenesis, forming an extracellular matrix.
Subsequently, remodelling creates a bone to implant interface which can be explained through distance and contact
osteogenesis. The dental implant surface has been shown to influence osteoconduction by modifying protein properties and adsorption around the implant. Salivary biomarkers may be considered as a specific and sensitive diagnostic
tool to detect these changes in protein expressions after implant placement. Thus, the purpose of this narrative review
is to provide a detailed account of the bone healing mechanism associated with dental implant placement, as well as
how the implant surface architecture and protein release play a role in bone healing, and the potential use of saliva
to detect these biomarkers.
4.Genetic Analysis of a Young Adult Presented with Acute Myocardial Infarction with No Traditional Risk Factors: A Novel Case Report
Huzairi Sani ; Lay Kek Teh ; Mohd Nur Fakhruzzaman Noorizhab ; Mohd Zaki Salleh ; Sazzli Shahlan Kasim
Malaysian Journal of Medicine and Health Sciences 2022;18(No.1):349-352
Myocardial infarction (MI) in the young adults are more common among the Asians compared to the Caucasians.
It is of great interest to investigate the genetic risks that increase the susceptibility of MI in young patients with no
family history. We conducted a genetic analysis on a young adult diagnosed with acute MI. The coronary angiogram
showed acute complete occlusion of the left anterior descending artery with 40% left ventricular ejection fraction
(LVEF). Patient’s DNA was subjected to genotyping using Infinium Asian Screening Array. The genotypes were annotated and associated with risks of cardiovascular diseases catalogued in GWAS database. Ninety-four genetic variants were detected. Patient has more than half of the genetic variants being homozygous risk genotypes for coronary
artery and coronary heart diseases. Identifying the potential genetic modifiers associated with MI in young patients is
of great interest to help the clinician make informed decisions to implement preventive and personalised medicine
for this patient.
5.Effects of proton pump inhibitor on the human gut microbiome profile in multi-ethnic groups in Singapore.
Seok Hwee KOO ; Jing DENG ; Daphne Shih Wen ANG ; John Chen HSIANG ; Lian Shien LEE ; Shafiq AAZMI ; Elsa Haniffah Mejia MOHAMED ; Hong YANG ; Siew Yoon YAP ; Lay Kek TEH ; Mohd Zaki SALLEH ; Edmund Jon Deoon LEE ; Tiing Leong ANG
Singapore medical journal 2019;60(10):512-521
INTRODUCTION:
The objectives of this study were to examine the effects of ethnicity, gender and a proton pump inhibitor (PPI), omeprazole, on the human gut microbiome. PPIs are commonly used for the treatment of acid-related disorders. We hypothesised that PPI therapy might perturb microbial communities and alter the gut microbiome.
METHODS:
Healthy subjects of Chinese (n = 12), Malay (n = 12) and Indian (n = 10) ancestry, aged 21-37 years, were enrolled. They provided a baseline stool sample (Day 1) and were then given a course of omeprazole at therapeutic dose (20 mg daily) for seven days. Stool samples were collected again on Day 7 and 14 (one week after stopping omeprazole). Microbial DNA was extracted from the stool samples, followed by polymerase chain reaction, library construction, 16S rRNA sequencing using Illumina MiSeq, and statistical and bioinformatics analyses.
RESULTS:
The findings showed an increase in species richness (p = 0.018) after omeprazole consumption on Day 7, which reverted to baseline on Day 14. There were significant increases in the relative abundance of Streptococcus vestibularis (p = 0.0001) and Veillonella dispar (p = 0.0001) on Day 7, which diminished on Day 14. Faecalibacterium prausnitzii, Sutterella stercoricanis and Bacteroides denticanum were characteristic of Chinese, Malays and Indians, respectively. Lactobacillaceae and Bacteroides xylanisolvens were the signature taxa of male and female subjects, respectively.
CONCLUSION
The study demonstrated alterations in the gut microbiome following omeprazole treatment. This may explain the underlying pathology of increased risk of Clostridium difficile infections associated with omeprazole therapy.