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Biomedical subjects

M C Wong

Publications and source records attributed to M C Wong.

At least 19 recordsLinked to original sources
PubMed2006

Association analysis of endothelial nitric oxide synthase gene polymorphism with primary hypertension in a Singapore population.

Vascular endothelial cells produce nitric oxide (NO), which contributes to the regulation of blood pressure and regional blood flow. Endothelial nitric oxide synthase (eNOS) gene polymorphisms are associated with coronary artery disease, but their linkage with primary hypertension is controversial. A total of 103 individuals with primary hypertension and 104 normotensive control subjects were studied in Singapore. The specific genotypes for G894T missense variant in exon 7, variable number tandem repeats (VNTR) in intron 4 (eNOS 4A/B/C) and T-786C in the promoter were isolated using allele-specific gene amplification and restriction fragment length polymorphism to examine the association of genotype and allelic frequency in both groups. Logistic regression analysis was also used to detect the association between genotypes and hypertension. Five genotypes of intron 4 VNTR (AA, AB, BB, AC and BC) were observed. Intron 4 B/B genotype was significantly associated with the hypertension group (P = 0.035), but disequilibrium of G894T and T-786C was absent between the two groups (P = 0.419 and P = 0.227), respectively. The overall distribution of allelic frequency differed significantly between the two groups, with four-repeat allele (4A) of intron 4 more frequent in the normotensive group than the hypertensive group (P = 0.019). Logistic regression analysis showed that intron 4 B/B genotype was significantly associated with systolic blood pressure of individuals with body mass index greater than 25 kg/m2 (P = 0.04). In conclusion, the eNOS 4 B/B genotype is a genetic susceptibility factor for primary hypertension in a Singapore population.

Blood Pressure↗
PubMed2006

The LRRK2 Gly2385Arg variant is associated with Parkinson's disease: genetic and functional evidence.

Evidence of LRRK2 haplotypes associated with Parkinson's disease (PD) risk was recently found in the Chinese population from Singapore, and a common LRRK2 missense variant, Gly2385Arg, was independently detected as a putative risk factor for PD in the Chinese population from Taiwan. To test the association between the Gly2385Arg variant in a large case-control sample of Chinese ethnicity from Singapore, and to perform functional studies of the wild type and Gly2385Arg LRRK2 protein in human cell lines. In a case-control study involving 989 Chinese subjects, the frequency of the heterozygous Gly2385Arg genotype was higher in PD compared to controls (7.3 vs. 3.6%, odds ratio = 2.1, 95% CI: 1.1-3.9, P = 0.014); these values yield an estimated population attributable risk (PAR) of approximately 4%. In a multivariate logistic regression analysis with the disease group (PD vs. controls) as the dependent variable and the genotype as an independent factor with adjustments made for the effect of age and gender, the heterozygous Gly2385Arg genotype remained associated with an increased risk of PD compared to wild type genotype (odds ratio = 2.67, 95% CI: 1.43-4.99, P = 0.002). The glycine at position 2385 is a candidate site for N-myristoylation, and the Gly2385Arg variant replaces the hydrophobic glycine with the hydrophilic arginine, and increases the net positive charge of the LRRK2 WD40 domain. In transfection studies, we demonstrated that both the wild type and Gly2385Arg variant LRRK2 protein localize to the cytoplasm and form aggregates. However, under condition of oxidative stress, the Gly2385Arg variant was more toxic and associated with a higher rate of apoptosis. Our study lends support to the contention that the Gly2385Arg is a common risk factor for PD in the Chinese population. Our bioinformatics and in-vitro studies also suggest that the Gly2385Arg variant is biologically relevant and it might act through pro-apoptotic mechanisms.

Aged↗
PubMed2006

Genetic analysis of SCA2, 3 and 17 in idiopathic Parkinson's disease.

Recent reports of SCA2 and SCA3 patients who presented with levodopa responsive parkinsonism have generated considerable interest as they have implications for genetic testing. It is unclear whether ethnic race alone or founder effects within certain geographical region explain such an association. In this study, we conducted genetic analysis of SCA2, 3, 17 in an ethnic Chinese cohort with early onset and familial Parkinson's disease (PD) and healthy controls. A total of 191 subjects comprising of 91 PD and 100 healthy controls were examined. We identified one positive case of SCA2 in an early-onset sporadic PD patient who had CAG 36 repeats, yielding a prevalence of 2.2% in early-onset sporadic PD patients and less than 1.0% in our study PD population. The size of the repeats was lower than the expanded repeats (38-57) in SCA2 patients with ataxia in our population. All the children of the patient were physically normal even though some of them carried the repeat expansion of similar size. No cases and controls were positive for SCA3 and SCA17. We do not think routine screening of SCA2, SCA3 and SCA17 for all idiopathic PD patients is cost-effective in our ethnic Chinese population. However, SCA2 should be a differential diagnosis in young onset sporadic PD when genetic mutations of other known PD genes have been excluded.

Adult↗
PubMed2006

Oligodendroglial tumor chemotherapy using "decreased-dose-intensity" PCV: a Singapore experience.

The authors propose "decreased-dose-intensity" PCV (procarbazine, lomustine [CCNU], and vincristine) chemotherapy for Asian patients with oligodendroglial tumors. In this study, all seven patients with oligodendroglioma (OD) and eight with anaplastic oligodendroglioma (AO) had objective responses or stable disease. Median progression-free survival was greater than 29 months (OD) and 36.5 months or greater (AO); 86% of patients with OD and 63% with AO remain progression-free. Twenty-four Common Toxicity Criteria Grade 3/4 adverse events were noted.

Adult↗
PubMed2005

Analysis of LRRK2 functional domains in nondominant Parkinson disease.

A comprehensive sequence analysis of 29 exons that code for the functional domains of LRRK2 in 160 nondominant Parkinson disease (PD) patients was performed. Novel variant screening in a further 470 sporadic PD patients and 630 controls revealed two novel variants (R1067Q and IVS33 + 6 T>A), which are likely to be pathogenic in five patients. One patient presented initially with a typical essential tremor phenotype, expanding the phenotypic spectrum of LRRK2 mutations.

Adult↗
PubMed2005

Impaired transcriptional upregulation of Parkin promoter variant under oxidative stress and proteasomal inhibition: clinical association.

We provided data to show that the transcriptional activity of wildtype -258T in the parkin promoter region was significantly higher than the -258G variant in human cell lines. The transcriptional activity of wildtype -258T was significantly increased under oxidative stress by hydrogen peroxide, but this was not observed for the -258G variant. The transcriptional upregulation was significantly higher for wildtype -258T compared to -258G variant at 0.1, 0.2 and 0.4 mM of hydrogen peroxide. Similar results were obtained when the cells were treated with a proteasome inhibitor, MG132.Furthermore, in a case control study involving 753 subjects, we demonstrated that the parkin promoter -258G variant was associated with an increased risk of sporadic Parkinson's disease (PD) in the elderly ethnic Chinese population. Our clinical and laboratory data provide corroborative evidence that some older individuals who have the -258G variant may have a higher risk of developing PD.

Age Factors↗
PubMed2005

The G2019S LRRK2 mutation is uncommon in an Asian cohort of Parkinson's disease patients.

A common heterozygous leucine-rich repeat kinase 2 (LRRK2) mutation 6055G > A transition (G2019S) accounts for about 3-7% of familial Parkinson's disease (PD) and 1-1.6% sporadic PD in a number of European populations. To determine the prevalence of the G1019S mutation in our Asian population, we conducted genetic analysis of this mutation in 1000 PD and healthy controls. The G2019S mutation was not detected in any of our study subjects. The prevalence of G2019S mutation is rare (< 0.1%) in our population, suggesting that occurrence of this mutation may vary amongst different ethnic races. This has important clinical implication when implementing guidelines for genetic testing.

Adolescent↗
PubMed2005

Differential expression of splice variant and wild-type parkin in sporadic Parkinson's disease.

BACKGROUND: Altered splicing of parkin under cellular stress could lead to changes in gene expression and altered protein activity. The causative role of parkin in sporadic Parkinson's disease (PD) is unknown. OBJECTIVES: We described a parkin splice variant (SV) in the substantia nigra and leukocytes of sporadic PD patients. Using a case control methodology, we investigated the exon 4 SV (E4SV) and wild-type parkin expression in the leukocytes of sporadic PD patients and healthy individuals. METHODS/RESULTS: We identified a parkin E4SV in the substantia nigra and leukocytes of sporadic PD patients and controls by reverse transcriptase-polymerase chain reaction (PCR). The exon 4 (122 bp) deletion resulted in a reading frame shift over the junction of exons 3-5 and a stop codon (tga) 17 bp downstream from exon 3. The translated truncated protein was associated with a total loss of the two-RING finger functional domain. Utilizing TaqMan real-time PCR with probes located across the junction of exons 3-4 or 3-5, we demonstrated an over-expression of E4SV/wild-type parkin ratio in the leukocytes of sporadic PD patients compared to age-, gender-, and race-matched controls (p<0.0005). A multivariate regression analysis demonstrated that the ratio of E4SV/wild-type parkin expression increased with age in PD patients, but this was not observed in the controls (p<0.0005). CONCLUSION: The relative expression of E4SV/wild type parkin was increased in sporadic PD compared to healthy controls. Based on our observations, further functional studies to determine the pathophysiologic role of E4SV in sporadic PD patients will be of importance.

Aged↗
PubMed2005

Prescribing pattern in Parkinson's disease: are cost and efficacy overriding factors?

Information on prescribing pattern of antiparkinsonian medications and factors influencing neurologists' choice of such drugs are important considerations in evaluating healthcare cost of Parkinson's disease (PD). We surveyed neurologists' perceived factors influencing their choice of drugs and actual prescribing pattern in PD. Three hundred and six patients at a tertiary hospital, diagnosed with idiopathic PD and who were dispensed antiparkinsonian drugs during a 6-month period were randomly selected. Patient demographics, type and dose of medications were analysed. A questionnaire survey evaluating the factors influencing choice of medications was administered to neurologists who practiced at the institution. The study population had a mean age of 64.4 years (SD +/- 9.9 years), and more than 80% were at Hoehn & Yahr stage 2-3. 92.3% of the study population were receiving levodopa and monotherapy, with levodopa being the most common treatment regimen. Patients who were prescribed levodopa were significantly older and at a later stage of disease compared to those without levodopa (p < 0.05). Only 26.8% of patients were prescribed dopamine agonists. In the survey, the neurologists cited severity of symptoms, and patients' intolerance of side effects, and efficacy as the most important factors influencing their choice of drugs. However, the actual prescribing pattern revealed a strong positive correlation of drug usage with cost subsidy by the institution. While factors affecting drug usage in PD are well recognised, cost and efficacy of a drug appear to be overriding practical factors in influencing usage pattern in clinical practice.

Aged↗
PubMed2005

Comparing 2-year outcomes of anterior cruciate ligament reconstruction using either patella-tendon or semitendinosus-tendon autografts: a non-randomised prospective study.

PURPOSE: To compare the results of anterior cruciate ligament (ACL) reconstructions using either a patella-tendon autograft or a semitendinosus-tendon autograft. METHODS: Based on surgeon experience and preference, 68 patients underwent ACL reconstruction using either a quadruple-strand semitendinosus autograft (n = 34) or a central one-third bone-patella tendon-bone autograft (n = 34). Each patient was assessed preoperatively and postoperatively at 3, 6, and 24 months using the International Knee Documentation Committee (IKDC) knee score, Biodex muscle strength and endurance testing, and the KT1000 instrumented arthrometer test of knee laxity to anterior translation. All assessments at the 2-year follow-up were performed by the same physician and physiotherapist. RESULTS: While ACL reconstruction improved knee stability and IKDC knee scores significantly, there was no statistically significant difference between semitendinosus- and patella-tendon autograft reconstructions in terms of long-term knee score or laxity to anterior translation. Semitendinosus graft reconstruction was associated with less donor-site morbidity and hamstring weakness. Meniscectomy was associated with poorer long-term knee scores. CONCLUSION: ACL reconstruction is associated with a significantly better IKDC knee score and laxity measurement at 2-year follow-up. However, we were unable to demonstrate a significantly better long-term outcome in knee score or laxity to anterior translation with either a patella-tendon autograft or a semitendinosus-tendon autograft.

Adolescent↗
PubMed2004

Fragile X premutation alleles in SCA, ET, and parkinsonism in an Asian cohort.

Among 367 subjects, the authors analyzed 167 patients with essential tremor, sporadic progressive cerebellar ataxia, multiple-system atrophy, and atypical parkinsonism and 200 healthy control subjects for FMR1 premutation alleles. None of the subjects carried alleles within the premutation range. These findings suggest that in the absence of other supportive clinical or imaging features, the cost-effectiveness of routine fragile X tremor/ataxia syndrome screening in this Asian cohort with movement disorders was low.

Adult↗
PubMed2004

Alpha-synuclein haplotypes implicated in risk of Parkinson's disease.

The authors examined four- and six-loci haplotype constructs (from five single nucleotide polymorphisms and three microsatellite regions) of the alpha-synuclein gene in patients with Parkinson's disease (PD) and controls in an ethnic Chinese population. Logistic regression analysis demonstrated an association of NACP-Rep1 (p = 0.002) and L478 (p < 0.0001) with risk of PD after correction for the effects of age, sex, and the other polymorphic loci. Specific four-loci and six-loci haplotypes were significantly associated with an increased or decreased risk of PD.

Adult↗
PubMed2004

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in a Chinese family: clinical, radiological and skin biopsy features.

We describe the clinical, radiological, genetic and skin biopsy findings of the first Chinese family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Of the 43-member family tree extending over three generations, eight had typical clinical features of CADASIL with recurrent ischemic stroke. In the three surviving affected family members, brain MRI showed extensive leukoaraiosis. Genotyping revealed heterozygous C to T mutation at nucleotide 406 in exon 3. Unusual clinical features were cerebellar infarction as a presenting complaint and a late age of onset with mild symptoms at age 69. A novel finding is the suggestion of a direct correlation between clinical disease severity and the quantity of ultrastructural pathognomonic granular osmophilic material (GOM) seen on skin biopsy.

Aged↗
PubMed2004

The lack of epidemiological link between the HIV type 1 infections in Hong Kong and Mainland China.

Blood samples were collected from 139 newly reported HIV-1 infections in Hong Kong over a 3-year period between 1999 and 2001, representing 22.8% of all reported cases. A majority of the patients were male (85.6%), Chinese (74%), and adult (97.1%) and acquired HIV-1 through sexual transmission (88.2%). The B and CRF01_AE were the major subtypes detected--49.6% and 44.6%, respectively. Over time, the frequency of CRF01_AE subtype increased, the B subtype decreased, and new subtypes of C (4) 2.8%, B' (1) 0.7%, and CRF07_BC (3) 2.2% emerged. The CRF01_AE subtype was commoner in female, Chinese, heterosexuals, and injection drug users whereas B subtype was commoner in male, white, and people with homosexual/bisexual contacts. There was no common source of infection from the analysis except a discernible cluster of Vietnamese injection drug users with the CRF01_AE subtype. The molecular findings did not suggest an epidemiological link between HIV infection in Hong Kong and Mainland China. Hong Kong's longstanding and extensive methadone treatment network may have contributed to the phenomenon.

Adult↗
PubMed2004

Pineal yolk sac tumour with a solid pattern: a case report in a Chinese adult man with Down's syndrome.

Intracranial germ cell tumours are rare. The incidence of primary intracranial yolk sac tumour is even more uncommon, with only two reported cases being associated with Down's syndrome in the English literature. This report details the findings of yolk sac tumour in the pineal region affecting a 22 year old Chinese man with Down's syndrome. Histology revealed yolk sac tumour with only a solid pattern, potentially mimicking the more common germinoma in the pineal region. No other germ cell components were identified. This is the third report of intracranial yolk sac tumour manifesting in a patient with trisomy 21. The pathology of this tumour and its differential diagnoses are discussed.

Adult↗