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Eng-King Tan

Publications and source records attributed to Eng-King Tan.

At least 37 records · Page 2Linked to original sources
PubMed2006

Polymorphisms in candidate genes: implications for the current treatment of Parkinson's disease.

Pharmacological treatment remains the cornerstone of therapy in Parkinson's disease. A number of clinical and genetic factors may influence the therapeutic response and treatment-related complications. Some exploratory studies have suggested that genetic polymorphisms may influence an individual's response to dopaminergic therapy and susceptibility to drug-related complications, such as hallucinations, dyskinesias, motor fluctuations and sudden onset of sleep episodes. This article provides a concise summary and discussion of the potential utility and limitation of studies that have examined the influence of genetic polymorphisms on drug-related response and complications in Parkinson's disease.

Animals↗
PubMed2006

Identification of a common genetic risk variant (LRRK2 Gly2385Arg) in Parkinson's disease.

The recent identification of a common genetic variant (LRRK2 G2385R) which is associated with a two-fold increased risk of sporadic Parkinson's Disease (PD) in two independent Chinese populations in Singapore and Taiwan has generated considerable excitement. Thus far, this variant appears specific for the Asian population, emphasising further that ethnic-specific effects should be considered in genetic association studies. Cautious optimism is advised as we await more scientific studies and clarification if this risk variant is specific to ethnic Chinese race. Our in-vitro studies suggest the Gly2385Arg variant is biologically relevant and it might act through pro-apoptotic mechanisms, especially under cellular stresses. This may provide a partial explanation why some carriers develop the disease while others do not. The presence of other epigenetic factors, gene-gene and gene-environmental interaction could modulate the phenotype expression. Further validation of these findings would be needed to confirm this variant as the single most important common genetic risk factor in ethnic Chinese and/or Asian PD patients. The identification of the LRRK2 Gly2385Arg variant could potentially facilitate the development of clinical, bioimaging, genetic and biological biomarkers, useful in the monitoring and neuroprotective therapy in asymptomatic individuals.

Asian People↗
PubMed2005

Analysis of LRRK 2 G 2019 S and I 2020 T mutations in Parkinson's disease.

Mutations in the leucine-rich repeat kinase 2 (LRRK 2), encoding dardarin protein, have been demonstrated to be linked to autosomal dominant Parkinson's disease (PD). In the present study the entire exon 41 of LRRK 2 gene was evaluated in a series of 174 PD patients recruited from Polish population, aged at the time of diagnosis 54.0+/-39.1 years, 21 of them had positive family history of PD with mean onset of the disease of 51.9+/-11.7 years as well as in 190 healthy controls aged 73.7+/-6.0 years. The mutations were evaluated by direct sequencing for mutations in exon 41 of LRRK 2 gene. In the studied patients no known mutations in exon 41 of LRRK 2 gene, including G 2019 S and I 2020 T were found, both in PD patients as well as in the controls. It can be concluded that the G 2019 S and I 2020 T mutations in exon 41 of LRRK 2 gene are rare causes of Parkinson disease in a Polish population.

Aged↗
PubMed2005

Comprehensive evaluation of common genetic variation within LRRK2 reveals evidence for association with sporadic Parkinson's disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder whose aetiologies are largely unknown. To date, mutations in six genes have been found causal for some rare familial forms of the disease and common variation within at least three of these is associated with the more common sporadic forms of PD. LRRK2 is the most recently identified familial PD gene, although its role in sporadic disease is unknown. In this study, we have performed the first comprehensive evaluation of common genetic variation within LRRK2 and investigated its contribution to risk of sporadic PD. We first characterized the linkage disequilibrium within LRRK2 using a panel of densely spaced SNPs across the gene. We then identified a subset of tagging-SNPs (tSNP) that capture the majority of common variation within LRRK2. Both single tSNP and tSNP haplotype analyses, using a large epidemiologically matched sporadic case-control series comprising 932 individuals, yielded significant evidence for disease association. We identified a haplotype that dramatically increases disease risk when present in two copies (OR=5.5, 95%CI=2.1-14.0, P=0.0001). Thus, we provide the first evidence that common genetic variation within LRRK2 contributes to the risk of sporadic PD in the Chinese population.

Adult↗
PubMed2005

Functional COMT variant predicts response to high dose pyridoxine in Parkinson's disease.

Pyridoxal-5-phosphate, the biological active form of pyridoxine, is a cofactor for dopa-decarboxylase (DDC) enzyme. Pyridoxine may augment the conversion of levodopa to dopamine in the periphery and therefore decrease availability of levodopa to the brain. However, this effect can be negated in the presence of a DDC inhibitor, which potentiates plasma levodopa level. A single nucleotide polymorphism at the nucleotide 1947 in the catechol-O-methyltransferase (COMT) gene encodes the high (COMT(H)) and low activity (COMT(L)) forms of the enzyme. In this study, we examined the effect of the COMT(L) allele on the clinical response to pyridoxine in Parkinson's disease (PD) patients. PD patients who were on stable and optimized dose of levodopa were included in this study. Their mean motor and activities of living score improved after high dose pyridoxine (P = 0.09, P = 0.04), and worsened after a washout period (P = 0.005, P = 0.001). Using a multivariate model, the presence of the COMT(L) allele predicted response to pyridoxine, with the best outcome observed in COMT(L/L) homozygotes. Our observational study suggests that the status the functional COMT(L) variant may be potentially useful to select PD patients for high dose pyridoxine therapy.

Activities of Daily Living↗
PubMed2005

Effect of MDR1 haplotype on risk of Parkinson disease.

BACKGROUND: MDR1, a multidrug transporter, encodes a P-glycoprotein that regulates the bioavailability of xenobiotics and is highly expressed at the blood-brain-barrier. Two single nucleotide polymorphisms (SNPs) (e21/2677[G/T/A] and e26/3435[C/T]) in the MDR1 gene can lead to differences in MDR1 expression and function. Specific MDR1 alleles of the 2 SNPs are positively selected among ethnic Chinese but not in the white population. OBJECTIVE: To determine whether specific haplotypes formed by SNPs e21/2677 and e26/3435 may protect against Parkinson disease (PD) among ethnic Chinese in Hong Kong. DESIGN: Case-control study. SETTING: Tertiary referral centers in Hong Kong. SUBJECTS: One hundred eighty-five patients with PD and 206 control subjects. INTERVENTIONS: The two SNPs were amplified in a single multiplex polymerase chain reaction. Five other SNPs that span 100 kilobases of the gene were also analyzed. MAIN OUTCOME MEASURES: Haplotypes frequencies, degree of haplotype association with the disease status, and estimated odds ratio for each haplotype with associated 95% confidence intervals. RESULTS: In addition to 2677 G-->T/A (exon 21) and 3435 C-->T (exon 26), the other SNPs that were analyzed were -41 A-->G (intron -1), -145 C-->G (exon 1), -129 T-->C (exon 1), 1236 T-->C (exon 12), and 4036 A-->G (exon 28). Haplotypes containing SNPs e21/2677 and e26/3435 were found to be significantly associated with risk of PD. In particular, the 2677T-3435T haplotype was strongly associated with a reduced risk of PD (P<.001; chi(2) = 14.521; odds ratio, 0.33; 95% confidence interval, 0.19-0.59). CONCLUSIONS: An MDR1 haplotype containing SNPs e21/2677T and e26/3435T protects against PD in ethnic Chinese, compatible with the observation of a recent positive selection of the T alleles of these 2 SNPs in this ethnic population.

Adult↗
PubMed2005

Alpha-synuclein mRNA expression in sporadic Parkinson's disease.

The expression of alpha-synuclein gene can be influenced by the genomic load and/or epigenetic factors. By using quantitative real-time polymerase chain reaction techniques, we demonstrated that the alpha-synuclein gene mRNA expression in sporadic PD did not differ from healthy controls (median [range] 0.110 ]0.012-0.628] vs. 0.120 [0.028-0.447]; P = 0.15). There was no difference in the alpha-synuclein gene dosage between PD patients with high and low mRNA expression. Multivariate analysis did not reveal age, gender, or cigarette smoking as confounding variables. Our study suggests that there was no significant alteration of alpha-synuclein mRNA expression in our sporadic PD patients compared to controls. However, the role of alpha-synuclein mRNA expression in select groups of sporadic PD patients and its interaction with environmental agents need to be further determined.

DNA Primers↗
PubMed2005

Alpha-synuclein and Parkinson's disease: implications from the screening of more than 1,900 patients.

Data on the frequency of alpha-synuclein mutations in Parkinson's disease (PD) are limited. Screening the entire coding region in 1,921 PD patients with denaturing high performance liquid chromatography and subsequent sequencing we only detected silent mutations (g.2654A>G, g.10151G>A, and g.15986A>T) and the c.209G>A substitution corresponding to the p.A53T mutation. These results demonstrate that mutations in the alpha-synuclein gene are rare and suggest that other factors contribute to alpha-synuclein aggregation in the majority of PD patients.

Aged↗
PubMed2005

Behind the facial twitch: depressive symptoms in hemifacial spasm.

BACKGROUND: Depression impairs psychosocial and occupational functioning and contributes to significant morbidity and mortality. Hemifacial spasm (HFS) causes social embarrassment and visual and verbal disability. OBJECTIVE: We examined; (1) the prevalence and predictive factors of depressive symptoms (Becks Depression Inventory (BDI) and clinical assessment) in HFS and (2) the sensitivity and specificity of BDI as a screening and diagnostic tool in HFS. METHODS: A large cohort of HFS patients in a movement disorders clinic was clinically evaluated and the BDI self-administered by patients. Univariate analysis and multivariate logistic regression were undertaken to investigate the effect of age, gender, body-mass index, duration and severity of HFS on the outcome of BDI score. ROC (receiver operating characteristics) analysis was utilized to evaluate the sensitivity and specificity and discriminative property of the scale. RESULTS: There were 90 HFS patients with a mean age of 54.4+11.1 (35-79) years, comprising of 58.9% women and with a mean severity HFS score of 2.9+0.8 (range 1-4). The mean BDI score was higher in depressed HFS than in non-depressed HFS (19.7+6.7 vs 4.2+4.9, p<0.0001). Female gender and a younger age were risk factors (p=0.07). In the multivariate analysis, the severity of HFS was an independent predictor of BDI scores (p<0.0001). The AUC was 97.1% suggesting excellent discriminative property of BDI. For cut-off score of 12/13, the sensitivity was 93.3%, specificity 94.7%, Positive Predictive Value 77.8% and Negative Predictive Value 98.6%. CONCLUSIONS: The prevalence of depressive disorder in HFS was 16.7%, with younger women at greater risk. The severity of HFS was positively correlated with the severity of depressive symptoms. The BDI can be a complimentary screening and/or diagnostic instrument for depressive disorder in HFS. Early diagnosis of at-risk patients will prevent unnecessary morbidity and mortality.

Adult↗
PubMed2004

Analysis of MDR1 haplotypes in Parkinson's disease in a white population.

The MDR1 multidrug transporter is important in regulating environmental xenobiotics and hence may play a causative role in Parkinson's disease (PD). MDR1 haplotype comprising 2677 G > T/A and 3435 C > T may be protective against PD. Using a case control methodology, we investigated the association of MDR1 haplotypes (single nucleotide polymorphisms (SNPs) 2677 G > T/A and 3435 C > T) in a Polish PD population. Seven SNPs, extending from the promoter to exon 28 of the MDR1 gene in 158 PD patients and 139 healthy controls were evaluated. Specifically we examined the association of haplotypes containing SNPs 2677 G > T/A and 3435 C > T and risk of PD. The multivariate logistic regression model was used to evaluate the effects of the covariates on the phenotypes. Haplotypes' frequencies were estimated using the Expectation-Maximization algorithm. The frequency of each individual SNPs; -41 A > G (intron -1), -145 C > G (exon 1), -129 T > C (exon 1), 1236 T > C (exon 12), 2677 G > T/A (exon 21), 3435 C > T (exon 26), and 4036 A > G (exon 28) did not differ between PD and controls. However, there was a trend towards significance in PD patients having the haplotype 2677G-3435C (p < 0.09, chi-square 2.85, odds ratio 0.25, 95% CI 0.06-1.08). Haplotype constructs of the other loci did not differ significantly between the two groups. There was a weak protective effect of the haplotype 2677G-3435C in our white population. However, the MDR1 haplotypes did not generally modulate the risk of PD.

Adult↗
PubMed2004

Genetic analysis of DJ-1 in a cohort Parkinson's disease patients of different ethnicity.

Mutations in the DJ-1 gene have been described in autosomal recessive Parkinson's disease patients (ARPD) of European ancestry and young onset (YOPD) Ashkenazi Jewish and Afro-Caribbean patients. There is little information on the prevalence of DJ-1 mutations amongst Asian PD populations. In this study, we examined for DJ-1 mutations in consecutive YOPD and ARPD in a multi-ethnic cohort (Chinese, Malays, and Indians) of PD patients in a tertiary referral center. Sequence analysis of all the exons and the exon and intron boundaries of the DJ-1 gene were carried out. We did not find any DJ-1 mutations in these patients. A number of intronic variants with genotype frequency ranging from 15 to 90% were detected. Unlike Parkin, pathogenic DJ-1 mutations appear to be restricted to certain populations and are unlikely to be of clinical importance in our Asian cohort.

Adult↗
PubMed2004

Botulinum toxin improves quality of life in hemifacial spasm: validation of a questionnaire (HFS-30).

BACKGROUND: Hemifacial spasm (HFS) can be disabling and affect quality of life. There is a lack of a validated scale for evaluating botulinum toxin (BTX) response in HFS. OBJECTIVE: We examined the validity and reliability of a self-rating health-related quality of life (HRQOL) questionnaire (HFS-30) in HFS and investigated the correlation of this questionnaire with the neurologists' assessment of severity of HFS and response to botulinum toxin (BTX) treatment. METHODS: HFS patients were asked to answer a total of 30 self-rating questions divided into seven subscales: Mobility; Activities of Daily Living (ADL); Emotional Well-being; Stigma; Social support; Cognition; and Communication. All of the items were scored on a 5-point scales ranging from 0 ("never") to 4 ("always"). They were also asked to assess their response to the BTX treatment based on a similar questionnaire at 6-8 weeks after BTX. The validity, reliability and sensitivity of the questionnaire were analyzed statistically. RESULTS: There were 80 HFS patients with mean age of 56.3+/-11.1 (S.D.) years (range 35 to 81), consisting of 54 (67.5%) females, 26 (32.5%) males. The intraclass correlation coefficient (ICC) and Cronbach's alpha were more than 0.7 for the majority of the items and subscales, respectively. There was a good positive correlation of severity of HFS with the subscale scores. Regression analysis of physicians' assessment of response to BTX on change in scores from baseline as rated by patients demonstrated a significant correlation. CONCLUSIONS: We demonstrated validity, reliability and sensitivity of the HFS-30 questionnaire. BTX improves quality of life in HFS.

Adult↗
PubMed2004

Severe bruxism following basal ganglia infarcts: insights into pathophysiology.

Bruxism characterized by clenching and grinding of teeth can lead to toothwear, headaches and depression. While bruxism has been associated with a number of neurological diseases, it has not been highlighted following cerebral infarction. An elderly man presented with an acute onset of tooth grinding and jaw clenching associated with dysarthria. His bruxism was worse during the day and resolved during sleep. He had frequent jaw aches, headaches and swallowing difficulty. Examination demonstrated the presence of dysarthria with jaw clenching and tooth grinding, producing persistent high pitch and loud squeaky sounds. A magnetic resonance imaging and angiography examination revealed a recent infarct in the right thalamus. In addition, chronic lacunar infarcts were present in the bilateral caudate nuclei with severe basilar artery stenosis. He was successfully treated with botulinum toxin. We discuss the pathophysiologic mechanisms of bruxism associated with basal ganglia infarcts. Dysfunction of the efferent and/or afferent thalamic or striatopallidal tracts may play a role in bruxism. Early recognition of bruxism following stroke could reduce unnecessary suffering since the condition can be effectively treated.

Basal Ganglia Cerebrovascular Disease↗
PubMed2004

An urge to move with L-thyroxine: clinical, biochemical, and polysomnographic correlation.

We report on the cause and effect relationship of restless legs syndrome (RLS) with L-thyroxine treatment in a hypothyroid patient with low serum ferritin. Upon challenge and withdrawal of L-thyroxine, there was a significant change in the International Restless Legs Syndrome Study Group severity score (26/40 to 6/40), the periodic limb movements (PMLS) index (20/hour to 10/hour), the number of arousals due to PLMS (59 to 22), sleep efficiency (74 to 85%), and biochemical parameters. RLS symptoms can complicate thyroxine replacement in at-risk hypothyroid patients with low serum ferritin. Early diagnosis and iron replacement could significantly reduce patient morbidity.

Ferritins↗
PubMed2004

Nurr1 mutational screen in Parkinson's disease.

We performed sequence analysis of all the exons and exon-intron boundaries in familial and young-onset Parkinson's disease (PD) in an Asian cohort. None of the patients carried any pathogenic mutations in the Nurr1 gene. We demonstrated a 5 to 10% prevalence of the intron 7 +33 C-->T variant among Malay and Indian PD and healthy controls, suggesting that this variant, which was previously described only in 1 Chinese patient, was not a silent mutation but a common polymorphic variant in some ethnic races.

Adult↗
PubMed2004

Polymorphism of renin-angiotensin system genes in IgA nephropathy.

BACKGROUND AND AIMS: Individuals are prone to disease because of certain disease-susceptible genes. The angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D), the angiotensinogen (AGT) gene, M235T, and the angiotensin II type 1 receptor (ATR) gene, A1166C, polymorphisms have been associated with IgA nephropathy (IgAN) and its progression. Several studies on Caucasians and Japanese patients have reported contradictory results. We determined these polymorphisms in 118 Chinese patients with IgAN and 94 healthy Chinese subjects to assess their clinical impact. METHODS: Genotyping was performed with DNA isolated from peripheral leucocytes, polymerase chain reaction amplification of the polymorphic sequence, restriction enzymes digestion, and separation and identification of DNA fragments. Clinical data at renal biopsy and final status on renal function were determined from patients' records. RESULTS: Comparing all IgAN patients with controls, AGT and ATR genotype distributions were similar, whereas there was a significant increase in the ACE DD genotype (P < 0.05). When comparing patients with end-stage renal failure (IgAN-ESRF) and those without (IgAN-nonESRF), there was no difference among the three gene polymorphisms. In contrast, there were significant differences in higher male prevalence (P < 0.05), increased serum creatinine at presentation (P < 0.05), more sclerosis (P < 0.01) and higher tubulointerstitial lesion score (P < 0.001) in the IgAN-ESRF group. CONCLUSION: Among the ACE, AGT and ATR gene polymorphisms, only the DD genotype may predispose the individual to IgAN in the Chinese population. None are significant for prognosticating ESRF.

Adult↗