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Biomedical subjects

Eng-King Tan

Publications and source records attributed to Eng-King Tan.

45 records · Page 3Linked to original sources

Renin-angiotensin system gene polymorphisms: its impact on IgAN and its progression to end-stage renal failure among Chinese in Singapore.

BACKGROUND: Gene polymorphisms in angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (ATR) had been associated with IgA nephropathy (IgAN) and its progression. Several studies on Caucasian and Japanese had reported contradicting results. We determined these polymorphisms in 118 Chinese patients with IgAN and 94 healthy Chinese to assess their clinical impact. METHODS: Genotyping was performed with DNA from peripheral leukocytes, PCR amplification of the polymorphic sequence, restriction enzymes digestion, separation and identification of DNA fragments. Clinical data at renal biopsy and final status on renal function were determined from patients' records. RESULTS: Among controls, genotype distributions were in Hardy-Weinberg equilibrium. Comparing all IgAN patients with controls, AGT and ATR genotype distributions were similar whereas there was significant increase in the ACE DD genotype (p < 0.05). Comparing patients with end-stage renal failure (IgAN-ESRF) and without (IgAN-nonESRF), there was no difference in any of the three gene polymorphisms. But 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 our Chinese population. In contrast to clinical and histological risk factors, these genetic variations showed no impact on disease progression to ESRF. It is unlikely that genotyping more patients will prove these genes useful. Nevertheless, preclinically determined genetic markers are very useful as risk factors for disease occurrence and as prognostic indices for disease progression. Therefore, continuing efforts should be made to look at other genes to find those with significance.

Adult↗

Psychogenic tics: diagnostic value of the placebo test.

Motor tics are characterized by abrupt onset of brief, unsustained focal movements that are usually preceded by a premonitory sensation and are suppressible. Psychogenic tics (pseudotics) are rarely described. It may not be easy to distinguish organic from functional tics because they can coexist. Using a case illustration, the value of a "staged" placebo test in aiding the diagnosis of psychogenic tics is described. In addition, a concise summary of the clinical phenomenology of tics and the diagnosis and management of psychogenic movement disorders is provided.

Child↗

Genetic analysis of Nurr1 haplotypes in Parkinson's disease.

Nurr1 gene plays an important role in the development of the mesencephalic dopaminergic system. Genetic variability of Nurr1 gene may be associated with risk of Parkinson's disease (PD). We found three polymorphic loci (c.-2922(C)2-3, IVS6+18insG and EX8+657 (9-10CA)) of the Nurr1 gene in our PD patients and a novel intron 7+33 C-->T variant in one PD patient. We proceeded to perform a haplotype analysis in a case control study. A total of 202 PD patients (mean age 65.04+/-9.44 years, 55.4% men) and 202 age, gender and race matched controls (mean age 64.33+/-10.12 years, 54.0% men) were studied. The intron 7+33 C-->T variant was present in only one of the PD patients (0.5%) but in none of the controls. The Nurr1 mRNA levels in the lymphocytes did not significantly differ between the affected patient and controls. We found complete linkage disequilibrium between c.-2922(C)2-3 and IVS6+18insG polymorphic loci (D=0.25). Analysis of the three loci haplotype frequencies did not demonstrate any significant difference between PD and controls. There were also no significant differences in the haplotype frequencies between young and late onset PD patients. In conclusion, we demonstrated a large common haplotype block spanning the Nurr1 gene in our population. The intron 7+33 C-->T variant most likely represents either a non-functional mutation or a rare polymorphism in our study population. Our study suggests that Nurr1 variability is unlikely to play a major role in the majority of our PD patients.

DNA-Binding Proteins↗

Alpha synuclein promoter and risk of Parkinson's disease: microsatellite and allelic size variability.

Polymorphism of the alpha synuclein promoter region (non-amyloid component of plaques (NACP)-Rep1) is associated with an increased risk of Parkinson's disease (PD) in three separate studies. We studied NACP-Rep1 polymorphism in two independent case control studies in our population. In study one, 104 PD and 104 age, gender and race matched controls; and in study two, 102 PD and 102 age, gender and race matched controls were examined separately. The results of both studies were analyzed independent of one another. We found three polymorphic alleles (designated 0, 1, 2). In study one, the frequency of allele 2 was significantly higher in PD patients as compared to healthy controls (0.37 versus 0.23, P=0.01, X(2)=9.98). In study two, the frequency of allele 2 was similar between PD and controls (0.31 versus 0.33, P=1.00, X(2)=0.30). There was a non-significant higher allele 2 frequency in PD when both studies were analyzed together (0.34 versus 0.28, P=0.20, X(2)=3.4). No significant differences of the various genotypes between PD and controls were found. However there were differences of the mixed dinucleotide repeats sequences for similar homozygous genotypes. Variability of the microsatellite region and potential interacting factors that could affect alpha synuclein gene transcription should be further examined.

Adult↗

Vascular parkinsonism in moyamoya: microvascular biopsy and imaging correlates.

We highlight the first case to our knowledge of vascular parkinsonism with angiographic moyamoya and functional imaging correlates. In addition, transmission electron microscopy of the cutaneous vasculature revealed the mean smooth muscle cell layer of the terminal arterioles to be significantly higher compared with ischemic stroke patients classified by vascular risk factors. Smooth muscle cell thickness was also greater in those with small vessel and large vessel strokes compared with cardioembolic strokes. The marked cutaneous arteriolar smooth muscle cell hypertrophy may be a useful surrogate marker for those at risk of developing angiographic moyamoya.

Arterioles↗

Dopamine D2 receptor TaqIA and TaqIB polymorphisms in Parkinson's disease.

In a case control study, we examined the association of DRD2 Taq1A and Taq1B polymorphisms and risk of PD, and evaluated the strength of linkage disequilibrium of the polymorphisms. The Taq1A and Taq1B polymorphisms were in strong linkage disequilibrium. There was, however, no significant association of the two polymorphisms with PD.

Alleles↗

Emerging therapeutic applications of botulinum toxin.

Botulinum toxin, the most potent known biological neurotoxin, holds great promise in the therapy of many diseases. It has been used effectively to treat strabismus, dystonias and other movement disorders, and spasticity. However, a number of potential new therapeutic indications have emerged and attracted a considerable amount of interest from the scientific community. These emerging indications included treatment for conditions associated with pain (e.g. headaches, myofascial pain, chronic low back pain), hypersecretion of glands (e.g. hyperhidrosis, sialorrhea, intrinsic rhinitis), and excessive or dyssynergic muscle contraction, and for cosmesis (e.g. myokymia, bruxism, anal fissure). There is a need for more controlled clinical trials, dose-ranging studies to determine optimal treatment, validated clinical scales and studies developed to assess the value of electromyographic guidance and skill of investigators on the outcome of treatment for some of these diseases. The long-term cost effectiveness of treatment and immunoresistance from repeated injections are also important clinical issues to address.

Botulinum Toxins↗