Chris Tan

Dose-dependent protective effect of coffee, tea, and smoking in Parkinson's disease: a study in ethnic Chinese

INTRODUCTION Few studies have examined the relationship of coffee and tea in Parkinsons disease (PD). The potential protective effect of coffee intake and risk of PD has not been studied in a Chinese population. There is a high prevalence of caffeine takers among Chinese in our population. OBJECTIVE We undertook a case control study to examine the relationship between coffee and tea drinking, cigarette smoking, and other enviromental factors and risk of PD among ethnic Chinese in our population. METHODS AND RESULTS 300 PD and 500 population controls were initially screened. Two hundred case control pairs matched for age, gender, and race were finally included in the analysis. Univariate analysis revealed significant association of PD with coffee drinking (p<0.0005), tea drinking (p=0.019), alcohol drinking (p=0.001), cigarette smoking (p<0.0005), and exposure to heavy metals (p=0.006). Conditional logistic regression analysis demonstrated that amount of coffee drunk (OR 0.787, 95%CI 0.664-0.932, p=0.006), amount of tea drunk (OR 0.724, 95%CI 0.559-0.937, p=0.014), number of cigarettes smoked (OR 0.384, 95%CI 0.204-0.722, p=0.003), history of heavy metal and toxin exposure (OR 11.837, 95%CI 1.075-130.366, p=0.044), and heart disease (OR 5.518, 95%CI 1.377-22.116, p=0.016) to be significant factors associated with PD. One unit of coffee and tea (3 cups/day for 10 years) would lead to a 22% and 28% risk reduction of PD. One unit of cigarette smoke (3 packs/day for 10 years) reduced the risk of PD by 62%. CONCLUSIONS We demonstrated a dose-dependent protective effect of PD in coffee and tea drinkers and smokers in an ethnic Chinese population. A history of exposure to heavy metals increased the risk of PD, supporting the multifactorial etiologies of the disease.

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 Parkinsons 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.

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 Parkinsons 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.

Monoamine oxidase B polymorphism, cigarette smoking and risk of Parkinson's disease: a study in an Asian population.

Cigarette smoking is associated with reduced monoamine oxidase B (MAO B) activity. Polymorphisms of the MAO B gene may modify the relationship between smoking and Parkinsons Disease (PD). We examined the association of MAO B intron 13 G/A polymorphism and risk of PD, and the modulation of the polymorphism on smoking and PD in an Asian study population in Singapore. Two hundred and thirty PD patients (mean age 66.0 ± 9.4 years, 63% men) and 241 age, gender, and race matched controls (mean age 64 ± 9.2 years, 58.9% males) were studied. The frequency of G and A alleles in PD and controls was; 66/315 (21.0%) vs. 73/340 (21.5%) and 249/315 (79.0%) vs. 267/340 (78.5%). For women, the genotype frequency in PD and controls was; GG: 7/85 (8.2%) vs. 8/99 (8.1%); GA: 25/85 (29.4%) vs. 27/99 (27.3%); AA: 53/85 (62.4%) vs. 64/99 (64.6%). For men, allele frequency in PD and controls was; A: 118/145 (81.4%) vs. 112/142 (78.9%) and G: 27/145 (18.6%) vs. 30/142 (21.1%). The allele and genotype frequencies were not significantly different between young and late onset PD. The frequency of “ever” smokers in PD and controls was 31/230 (13.5%) vs. 52/241 (21.6%), P = 0.02. A stepwise logistic regression analysis did not reveal any interaction of smoking and the G allele and risk of PD. The MAO B G/A genotype frequency in our Asian population was quite different from Caucasians suggesting that ethnicity specific effects need to be considered in evaluating gene‐environmental interaction.

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 Parkinsons 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.

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.

Nurr1 mutational screen in Parkinson's disease

We performed sequence analysis of all the exons and exon–intron boundaries in familial and young‐onset Parkinsons 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.

Transcranial magnetic stimulation screening for cord compression in cervical spondylosis

OBJECTIVE Cervical spondylosis (CS) often results in various degrees of cord compression, which can be evaluated functionally with transcranial magnetic stimulation (TMS). We investigate the use of TMS as a screening tool for myelopathy in CS. METHODS We prospectively studied 231 patients classified into Groups 1 to 4 based on MRI grading of severity of cord compromise. TMS elicited central motor conduction times and motor evoked potential (MEP) amplitudes in all 4 limbs. The results were compared with those from 45 healthy controls. RESULTS TMS showed 98% sensitivity and 98% specificity for cord abnormality using MRI as reference standard. CONCLUSIONS MEP abnormalities are useful for electrophysiological evaluation of cord compression in CS. While TMS is not a substitute for MRI, it is of value as a rapid, inexpensive and non-invasive technique for screening patients before MRI studies.

Cutaneous silent periods in the evaluation of cord compression in cervical spondylosis

ObjectiveThe clinical diagnosis of cervical spondylotic myelopathy (CSM) may be challenging in patients with cervical spondylosis (CS). Routine nerve conduction studies (NCS) may not evaluate cord compression adequately.MethodsWe obtained cutaneous silent periods (CSP) in 26 consecutive patients presenting with clinical features of CS, in comparison with 30 normal controls. The results were also compared with transcranial magnetic stimulation (TMS) findings, and magnetic resonance imaging of the cervical cord as the gold standard.ResultsCSP findings showed similarly high sensitivity of up to 96% with TMS in evaluating cervical cord dysfunction.ConclusionIn specific clinical settings, CSP is of value for the diagnosis of CSM in CS. CSP measurement is advocated as a simple and rapid diagnostic adjunct to NCS in evaluating CS patients with possible cord compromise.

Intraoperative monitoring study of ipsilateral motor evoked potentials in scoliosis surgery

Ipsilateral motor evoked potentials (MEPs) in spinal cord surgery intraoperative monitoring is not well studied. We show that ipsilateral MEPs have significantly larger amplitudes and were elicited with lower stimulation intensities than contralateral MEPs. The possible underlying mechanisms are discussed based on current knowledge of corticospinal pathways. Ipsilateral MEPs may provide additional information on the integrity of descending motor tracts during spinal surgery monitoring.