Impact of socioeconomic status on vision-related quality of life in primary open-angle glaucoma.

PurposeTo investigate the impact of socioeconomic status (SES) on vision-related quality of life (VRQOL) in patients with primary open-angle glaucoma (POAG).Patients and methodsThis prospective cross-sectional study included consecutive patients with POAG at a tertiary hospital between March 2012 and January 2013. All patients had visual acuity no worse than 20/60 in the better eye and reliable visual field tests. VRQOL was assessed by the validated Taiwan version 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25). Sociodemographic characteristics, medical history, and ocular parameters were recorded. SES was evaluated based on educational attainment and monthly income, both stratified into three levels. Analysis of variance and linear regression analysis were used to evaluate the relationship between SES, VRQOL, and clinical parameters.ResultsAmong the 186 patients recruited, intergroup differences were not observed among educational or monthly income levels for binocular vision or integrated visual field defects. Patients of lower educational and monthly income levels had lower self-reported general health ratings. After adjustment for visual function, treatment complexity, and general health in the multiple linear regression model, patients with a college degree or higher reported better NEI VFQ-25 scores for the composite score (P=0.041), mental health (P=0.035), and peripheral vision (P=0.05) than did those with education below junior high school. Monthly income levels did not affect the NEI VFQ-25 scores.ConclusionEducational attainment significantly affects VRQOL in patients with POAG. Additional counseling may be provided to patients with lower educational background to help them cope with the disease.

Seven-year incidence of uncorrected refractive error among an elderly Chinese population in Shihpai, Taiwan: The Shihpai Eye Study.

PURPOSE: To report the 7-year incidence of uncorrected refractive error in a metropolitan Chinese elderly population. METHODS: The Shihpai Eye Study 2006 included 460/824 (55.8%) subjects (age range 72-94 years old) of 1361 participants in the 1999 baseline survey for a follow-up eye examination. Visual acuity was assessed using a Snellen chart, uncorrected refractive error was defined as presenting visual acuity (naked eye if without spectacles and with distance spectacles if worn) in the better eye of <6/12 that improved to no impairment (≥6/12) after refractive correction. RESULTS: The 7-year incidence of uncorrected refractive error was 10.5% (95% confidence interval (CI): 7.6-13.4%). 92.7% of participants with uncorrection and 77.8% with undercorrection were able to improve at least two lines of visual acuity by refractive correction. In multivariate analysis controlling for covariates, uncorrected refractive error was significantly related to myopia (relative risk (RR): 3.15; 95% CI: 1.31-7.58) and living alone (RR: 2.94; 95% CI 1.14-7.53), whereas distance spectacles worn during examination was protective (RR: 0.35; 95% CI: 0.14-0.88). CONCLUSION: Our study indicated that the incidence of uncorrected refractive error was high (10.5%) in this elderly Chinese population. Living alone and myopia are predisposing factors, whereas wearing distance spectacles at examination is protective.

Increased level of MSU crystal-bound protein apolipoprotein A-I in acute gouty arthritis.

BACKGROUND: Gout is a common form of inflammatory arthritis that is triggered by the crystallization of monosodium urate (MSU). We investigated the potential proteins that relate to the pathogenesis or the spontaneous resolution of acute gouty arthritis. METHOD: We screened for differentially expressed proteins in the plasma of patients with acute gouty arthritis using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) identification. We confirmed these findings in a population study of 209 subjects, and further determined the protein profile of the synovial fluid (SF) from 24 gouty patients during acute attack by liquid chromatography coupled with tandem MS (LC/MS/MS). RESULTS: The highly expressed apolipoprotein A-I (apoA-I) was identified in the plasma of acute gouty patients compared with healthy controls. Moreover, we detected high levels of SF apoA-I in 83.3% of acute gouty patients during attack. From the population study, apoA-I was increasingly associated with normouricaemia, hyperuricaemia, and acute gouty arthritis (ptrend < 0.001), and plasma uric acid (UA) and apoA-I were positively correlated (p = 0.0156). We used a human liver cell model and found that UA enhanced the hepatic apoA-I mRNA expression level (ptrend < 0.01) and apoA-I secretion level (ptrend = 0.002) in a dose-dependent manner. An elevated MSU concentration caused the endogenous apoA-I to deplete gradually. CONCLUSIONS: Based on the role of apoA-I in anti-inflammation, our observational data in acute gout support the hypothesis that apoA-I expression can be induced under the condition of a high concentration of UA and its elevated level may be implicated in the spontaneous resolution of acute gouty arthritis.

Hepatotoxicity of anti-tuberculosis chemotherapy in patients with liver cirrhosis.

OBJECTIVE: To determine whether liver cirrhosis patients are at higher risk for drug-induced hepatotoxicity (DIH) than control subjects during treatment for tuberculosis (TB) with standard short-course regimens containing isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and/or pyrazinamide (PZA). METHODS: Fifty liver cirrhosis patients with newly diagnosed active TB treated with INH, RMP, EMB and/or PZA were included in the study, along with 147 patients without liver disease selected as control subjects. DIH was defined as alanine aminotransferase (ALT) > 120 IU/l with hepatitis symptoms or ALT > 200 IU/l. RESULTS: The aetiology of the liver cirrhosis patients consisted of alcoholic liver cirrhosis (n = 37, 74%), hepatitis B (n = 10, 20%) and hepatitis C (n = 3, 6%). The mean Child-Pugh score of all liver cirrhosis patients was 7.0 ± 1.2. DIH was more frequently found in liver cirrhosis patients, but the difference was not statistically significant (8.0% vs. 2.7%, P = 0.115). INH and RMP were successfully rechallenged and maintained until the end of treatment in three of four liver cirrhosis patients with DIH. CONCLUSION: Although DIH developed more frequently in TB patients with liver cirrhosis, the apparent difference in the incidence of DIH did not achieve statistical significance. Most of the patients with DIH were successfully treated with a standard short-course regimen including INH and RMP.

Androgen receptor-mediated apoptosis in bovine testicular induced pluripotent stem cells in response to phthalate esters.

The androgen receptor (AR) has a critical role in promoting androgen-dependent and -independent apoptosis in testicular cells. However, the molecular mechanisms that underlie the ligand-independent apoptosis, including the activity of AR in testicular stem cells, are not completely understood. In the present study, we generated induced pluripotent stem cells (iPSCs) from bovine testicular cells by electroporation of octamer-binding transcription factor 4 (OCT4). The cells were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4, which maintained and stabilized the expression of stemness genes and pluripotency. The iPSCs were used to assess the apoptosis activity following exposure to phthalate esters, including di (2-ethyhexyl) phthalates, di (n-butyl) phthalate, and butyl benzyl phthalate. Phthalate esters significantly reduced the expression of AR in iPSCs and induced a higher ratio of BAX/BCL-2, thereby favoring apoptosis. Phthalate esters also increased the expression of cyclin-dependent kinase inhibitor 1 (p21(Cip1)) in a p53-dependent manner and enhanced the transcriptional activity of p53. The forced expression of AR and knockdown of p21(Cip1) led to the rescue of the phthalate-mediated apoptosis. Overall, this study suggests that testicular iPSCs are a useful system for screening the toxicity of environmental disruptors and examining their effect on the maintenance of stemness and pluripotency, as well as for identifying the iPSC signaling pathway(s) that are deregulated by these chemicals.

Psoriasis as initiator or amplifier of the systemic inflammatory march: impact on development of severe vascular events and implications for treatment strategy.

BACKGROUND: Psoriasis is a systemic disease associated with metabolic disorders and vascular complications. Both psoriasis and metabolic disorders are associated with systemic inflammation. We hypothesized that the sequence of events between the onset of psoriasis and metabolic disorder may affect the risk for subsequent development of vascular complications. METHODS: Nested case-control study was performed using the Taiwan National Health Insurance database. Accordingly, a total of 8180 psoriatic patients and 163,600 controls were included. Psoriasis was considered as the initiator of inflammatory march if metabolic disorder, including hypertension, diabetes mellitus and dyslipidemia, developed after onset of psoriasis. In patients with pre-existing metabolic disorder, psoriasis was considered as the amplifier of inflammatory march. RESULTS: In patients whose psoriasis served as the disease initiator, a lower risk for developing vascular disease (HR = 1.49; 95% CI = 1.11-2.00 and HR = 1.64; 95% CI = 1.31-2.05 for cerebrovascular and cardiovascular events, respectively) was found compared with patients whose psoriasis served as the disease amplifier (HR = 2.26; 95% CI = 1.72-2.97 and HR = 2.78; 95% CI = 2.26-3.42 for cerebrovascular and cardiovascular events, respectively) after adjusting for age and gender. In terms of treatment implications, methotrexate was associated with reduced risk for developing cerebrovascular event (HR = 0.22; 95% CI = 0.05-0.88) only in patients with psoriasis serving as the disease amplifier. CONCLUSIONS: Our results suggested that two scenarios of systemic inflammatory marches are present among psoriatic patients with metabolic disorder and judicious use of methotrexate may reduce the risk of cerebrovascular event, especially when psoriasis served as the disease amplifier of the systemic inflammatory march.

Mechanistic correlations between two itch biomarkers, cytokine interleukin-31 and neuropeptide ß-endorphin, via STAT3/calcium axis in atopic dermatitis.

BACKGROUND: Itch is the cardinal symptom of atopic dermatitis (AD). ß-Endorphin, a neuropeptide, is increased in both AD skin and sera. Interleukin (IL)-31, an itch-relevant cytokine, activates IL-31 receptors in keratinocytes. However, how IL-31 and ß-endorphin interact in AD skin remains elusive. OBJECTIVES: To investigate the mechanistic interaction of IL-31 and ß-endorphin in AD. METHODS: This was a prospective cross-sectional study. We recruited adult patients with AD and controls according to Hanifin's AD criteria. Serum levels of IL-31 and ß-endorphin were measured by enzyme-linked immunosorbent assay. Expressions of IL-31 receptor A (IL-31RA) and ß-endorphin in the skin were assessed by immunohistochemistry. Their expression in the skin and blood was compared and correlated in patients with AD and in controls. We also treated primary keratinocytes with IL-31 and measured calcium influx, ß-endorphin production and signalling pathways to define their mechanistic interactions. RESULTS: ß-Endorphin was increased in the supernatant from IL-31-treated keratinocytes. IL-31 receptor activation resulted in calcium influx and STAT3 activation; pretreatment with STAT3 inhibitor stopped the increase of ß-endorphin. Notably, either replacement of extracellular calcium or treatment with 2-aminoethoxydiphenyl borate, an inhibitor for the store-operated channel, blocked STAT3 activation. We found higher levels of blood ß-endorphin and IL-31, which were significantly correlated, in patients with AD. Moreover, IL-31RA and ß-endorphin were increased and colocalized both in AD human skin and TPA-painted mouse skin. CONCLUSIONS: IL-31 receptor activation in keratinocytes induces calcium influx and STAT3-dependent production of ß-endorphin. These results might contribute to an understanding of the regulatory mechanisms underlying peripheral itch.

The polymorphisms of C-reactive protein gene modify the association between central obesity and lung function in taiwan asthmatics.

High-sensitivity C-reactive protein (hs-CRP) concentrations and obesity are proposed to have a significant relationship with impairment of lung function, but little has been reported to date on the association between CRP gene and lung function. We studied the association of three tagSNPs (tag single nucleotide polymorphisms) of CRP gene and their interactions with central obesity on lung function. A total of 384 asthmatic adults and 384 controls who were 1:1 matched by sex and age were recruited for this study. Three tagSNPs polymorphisms for CRP rs1417938, rs1800947 and rs1205 were selected from HapMap data and genotyping by using TaqMan allelic discrimination assay. A questionnaire interview, body composition and pulmonary function tests were performed. CRP single nucleotide polymorphisms (SNPs) did not increase the risk of asthma, but CRP rs1205 CC genotype significantly decreased the predictive value of forced vital capacity (FVC) in the asthma group (adjusted mean change = -7.54%, 95% CI = -13.82 to -1.25%). Waist-to-hip ratio, not body mass index, also decreased the predictive value of FVC in asthmatics. The subjects with central obesity who carried CRP SNPs have a significant reduction effect in lung function. The current results suggest that central obesity may play a major role in lung function, and these effects were modified significantly by the polymorphisms for CRP gene.

Role of gender disparity of circulating high-sensitivity C-reactive protein concentrations and obesity on asthma in Taiwan.

BACKGROUND: Several studies have suggested that the association between obesity and asthma may be stronger in females than in males, but the reason is still unclear. OBJECTIVE: The aim of this study was to investigate whether differences in high-sensitivity C-reactive protein (hs-CRP) levels explain why obesity is associated with asthma in females but not in males. METHODS: This study prospectively enrolled 754 subjects ≥ 18 years old from hospital-based asthma patients and population-based controls. We measured adiposity factors [body mass index (BMI), waist circumference and waist-hip ratio], hs-CRP and total IgE levels. RESULTS: After adjusting for potential confounding factors, we found a significant association between BMI and asthma in females with a significant interaction of gender and BMI on asthma (χ(2) =10.2, P=0.004). If hs-CRP was added to the logistic model, the interaction was attenuated but still significant (χ(2) =7.02, P=0.03). After adjusting for BMI, we did not find that circulating hs-CRP concentrations were significantly associated with asthma in males and females. CONCLUSION: We found that BMI was associated with asthma in females, but our results do not support the suggestion that hs-CRP levels contribute significantly to the link between obesity and asthma with respect to gender disparity.

Signalling pathway of isophorone diisocyanate-responsive interleukin-8 in airway smooth muscle cells.

This study is the first to analyse the soluble factors secreted by the bronchial epithelium after exposure to isophorone diisocyanate (IPDI) that are responsible for increasing migration and proliferation of primary normal human bronchial smooth muscle cells (BSMCs). We treated immortalised, nontumorigenic human bronchial epithelial cells (cell line BEAS-2B) and primary normal human bronchial epithelial cells (HBEC) with IPDI, and then collected the conditioned culture media (IPDI-BEAS-2B-CM and IPDI-HBEC-CM, respectively), which was added to BSMCs. Exposure of BEAS-2B cells and HBECs to IPDI increased interleukin (IL)-8 production. Culture of BSMCs with IPDI-BEAS-2B-CM and IPDI-HBEC-CM increased BSMC proliferation and migration, which are major features in asthma-related airway remodelling. Induction of BSMC proliferation and migration by IPDI-BEAS-2B-CM and IPDI-HBEC-CM was associated with increased focal adhesion kinase (FAK), Src, extracellular signal-regulated kinase (ERK)1/2 and AKT activation. Blocking FAK with a specific inhibitor significantly decreased BSMC migration and proliferation by inhibiting ERK1/2 activation. FAK and ERK1/2 inhibitor also decreased IPDI-BEAS-2B-CM-, IPDI-HBEC-CM- and recombinant human IL-8-mediated BSMC proliferation and migration, whereas blocking Rnd3 using small interfering RNA failed to affect BSMC proliferation, suggesting that Rnd3 was only involved in the regulation of BSMC migration. Our study suggests that inhibition of IL-8 or IL-8-mediated FAK/ERK/Rnd3 signalling is an attractive therapeutic target for IPDI-mediated asthma.

Lifetime exposure to cigarette smoking and the development of adult-onset atopic dermatitis.

BACKGROUND: Adult-onset atopic dermatitis (AD) has recently been recognized as a distinct disease entity, but its risk factors have not yet been clearly defined. Although gestational and perinatal exposure to tobacco smoking may be associated with the development of classic AD, the association between active/passive smoking and adult-onset AD remains controversial. OBJECTIVES: To determine if exposure to smoking, including environmental tobacco smoke (ETS), is associated with the risk of adult-onset AD. METHODS: Tobacco smoking and exposure to ETS were measured in a case-control association analysis in 83 patients with physician-diagnosed adult-onset AD and 142 age- and sex-matched controls. RESULTS: Multiple logistic regression analyses showed that, among the potential environmental risk factors, both current and ever smoking were significant risk factors for adult-onset AD [odds ratio (OR) 4·994 and 3·619, respectively], compared with never smoking. Also, packs per year was significantly associated with adult-onset AD (OR 1·058, 95% confidence interval 1·028-1·089), suggesting a lifelong cumulative risk in current smokers. Moreover, nonsmokers with adult-onset AD reported significantly more exposure to ETS. CONCLUSIONS: Early and/or current exposure to cigarette smoking may contribute cumulatively to the development of adult-onset AD. Exposure to ETS in childhood is associated with the development of adult-onset AD. Adults should be discouraged from smoking to prevent adult-onset AD in themselves and their family members.

Playing saxophone induced diffuse alveolar hemorrhage: a case report.

INTRODUCTION: The blood-gas barrier must be very thin to allow gas exchange and it is therefore subjected to high mechanical stresses when the capillary pressure rises. Exercise-induced pulmonary hemorrhage (EIPH) occurs frequently in horses and there is evidence that EIPH can also occur in humans. MATERIALS AND METHODS: We reported on a healthy 65-year-old male who developed a diffuse alveolar hemorrhage (DAH), like an EIPH, after playing saxophone for 6 h continuously. There were hemoptysis, crackles breathing sounds on exam, and bilateral radiographic infiltrates. A high-resolution computed tomographic study of the thorax disclosed DAH, the presence of which was proved by a gross appearance of bilateral bronchus on bronchoscopy and histopathological study of bronchoalveolar lavage material. CONCLUSION: This is the first report of alveolar hemorrhage caused by playing saxophone. In our case, he presented with a benign course and regressed spontaneously without any medical intervention.

Peri-ictal normalization of visual cortex excitability in migraine: an MEG study.

To delineate if the change in cortical excitability persists across migraine attacks, visual evoked magnetic fields (VEF) were measured in patients with migraine without aura during the interictal (n = 26) or peri-ictal (n = 21) periods, and were compared with 30 healthy controls. The visual stimuli were checkerboard reversals with four different check sizes (15', 30', 60' and 120'). For each check size, five sequential blocks of 50 VEF responses were recorded to calculate the percentage change of the P100m amplitude in the second to the fifth blocks in comparison with the first block. At check size 120', interictal patients showed a larger amplitude increment than controls [28.1 +/- 38.3% (s.d.) vs. 8.7 +/- 21.3%] in the second block and a larger increment than peri-ictal patients in the second (28.1 +/- 38.3% vs. -3.2 +/- 19.2%), fourth (22.7 +/- 31.2% vs. -5.7 +/- 22.3%) and fifth (20.5 +/- 30.4% vs. -10.8 +/- 30.1%) blocks (P < 0.05). There was no significant difference at other check sizes or between peri-ictal patients and controls. In conclusion, there may be peri-ictal normalization of visual cortical excitability changes in migraine that is dependent on the spatial frequency of the stimuli and reflects a dynamic modulation of cortical activities.

Association study between keratinocyte-derived growth factor gene polymorphisms and susceptibility to vitiligo vulgaris in a Taiwanese population: potential involvement of stem cell factor.

BACKGROUND: Vitiligo vulgaris is a depigmentary disorder resulting from the disappearance of functional melanocytes. Currently, the pathogenesis of this disorder remains obscure. OBJECTIVES: Genetic analysis of patients with vitilgo may provide important clues for elucidating the complex pathomechanisms involved in the disease process. Because dysfunctional keratinocytes have recently been implicated in the pathogenesis of vitiligo vulgaris, we conducted a case-control association study to investigate this phenomenon. PATIENTS AND METHODS: Fifty-one patients with vitiligo vulgaris and 118 healthy controls from Taiwan were recruited to investigate the association between relevant keratinocyte-related genes and the occurrence of vitiligo vulgaris. This study genotyped 11 single-nucleotide polymorphisms (SNPs) in five genes including stem cell factor (SCF, also known as KITLG), basic fibroblast growth factor (bFGF, also known as NuDT6), endothelin-1 (EDN1), hepatocyte growth factor (HGF) and stem cell growth factor (SCGF, also known as CLEC11A). RESULTS: Our results revealed that the A allele for SNP rs11104947 in the SCF gene and the T allele for SNP rs13866 in the SCGF gene were, respectively, associated with a 1.95- and a 2.14-fold risk of developing vitiligo vulgaris. A higher risk was also detected among subjects who carried the SCF rs995029/rs11104947 C/A haplotype (odds ratio = 2.45). Furthermore, the at-risk alleles for SCF rs11104947 (A allele) and for SCGF SNP rs13866 (T allele) were found to display a 7.92-fold increased gene-gene combined risk. No significant relationship between polymorphic frequency for genes bFGF, EDN1 as well as HGF and occurrence of vitiligo vulgaris was observed. CONCLUSIONS: These novel genetic findings provide new insights in relation to the mechanisms that might be involved in the development of vitiligo vulgaris.

The cyclic GMP-dependent protein kinase II gene associates with gout disease: identified by genome-wide analysis and case-control study.

OBJECTIVE: To identify the position of a gout susceptibility gene. METHODS: A genome-wide scan was performed using 382 random polymorphic microsatellite markers spread across 22 autosomes in a Taiwanese family with gout to screen for the gout susceptibility genetic marker. Its association with gout by 33 single nucleotide polymorphisms (SNP) in 148 matched case-control subjects was confirmed. The family with gout comprised eight patients with gout and 10 gout-free subjects; case-control subjects were 74 male patients with gout and 74 healthy controls matched by age. RESULTS: Analysis of the genome-wide scan results by a non-parametric linkage method found that chromosome 4q21 contains a locus significantly linked with gout (D4S3243 at 81 289 553 bp; p = 0.004; LOD score = 5.13). In SNP genotyping analysis at the neighbourhood regions of marker D4S3243 for the case-control subjects, the polymorphisms rs7688672 and rs6837293, located on the cGMP-dependent protein kinase II (cGK II) gene, were found to relate significantly to gout disease in a recessive model after adjustment of hyperuricaemia (OR = 2.89, 95% CI 1.19 to 7.02 and OR = 2.72, 95% CI 1.13 to 6.54, respectively). CONCLUSIONS: This study suggests that the cGK II gene on chromosome 4q21 is most likely to harbour gout disease independently of hyperuricaemia and is inherited recessively.

Associations between gout tophus and polymorphisms 869T/C and -509C/T in transforming growth factor beta1 gene.

OBJECTIVES: To investigate the associations between gout tophus and polymorphisms 869T/C and -509C/T in TGF-beta1 gene. METHODS: The polymorphisms 869T/C and -509C/T were determined in 73 gout patients and 114 healthy controls among male Taiwanese using the PCR-restriction fragment length polymorphism method. Each patient was matched with 1-2 controls by age within 1-2 yrs. The tophus number was measured from all the patients' arms and legs. RESULTS: Neither 869T/C nor -509C/T showed a significant association between patients and controls in the proportions of genotypes, allele frequency or dominant and recessive models. The mean number of tophi for all patients was 1.53 +/- 3.44, showing a significant difference in distribution among the genotypes at polymorphism 869T/C (P = 0.006), but not those in polymorphism -509C/T (P > 0.05). Those carrying genotype CC at polymorphism 869T/C have a mean number of tophi 0.35 (+/- 1.11), which is significantly lower than those carrying genotype TT (3.73 +/- 4.67; P < 0.05). Those with genotype TT at polymorphism 869T/C also had 11.06 times the likelihood of having at least one tophus compared with the genotype CC after adjustment of hyperuricaemia (95% CI = 1.84, 66.36; P = 0.009). However, except for the tophus number, these two polymorphisms did not show any significant association with the clinical characteristics or biochemical markers. CONCLUSIONS: The polymorphism 869T/C in TGF-beta1 gene has a significant association with the occurrence of tophus in gout patients.

The polymorphism -863C/A in tumour necrosis factor-alpha gene contributes an independent association to gout.

OBJECTIVE: To investigate the associations between polymorphisms in the promoter of the tumour necrosis factor-alpha (TNF-alpha) gene and gout. METHODS: The polymorphisms -308G/A and -863C/A in the TNF-alpha gene were determined in 106 gout patients and 159 healthy controls among male Taiwanese using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The biochemical markers, including Glutamic-oxaloacetic transaminase (GOT), Glutamic-pyruvic transaminase (GPT), uric acid, creatinine, total cholesterol (TC), triglycerides (TG), body mass index (BMI) and hypertension, as well as alcohol consumption were measured. RESULTS: The gout patients had 9.43% (10/106) with genotype AA at polymorphism -863C/A showing a significantly higher fraction than controls (0.63%; 1/159, P < 0.001). The crude results also showed that the gout patients had significantly higher portions of abnormal GOT, GPT, creatinine, TC, TG, alcohol consumption, hypertension and hyperuricaemia than controls (P < 0.05), but the -308G/A, BMI and genotype CA at -863C/A did not show the same significant difference (P > 0.05). After adjustment by a stepwise logistic regression method, the hyperuricaemia, creatinine, GPT, TG and alcohol consumption as well as genotype AA at polymorphism -863C/A were found to be significantly associated with gout. CONCLUSION: The genotype AA at polymorphism -863C/A in a recessive model showed a significant association with developing gout independent of hyperuricaemia, abnormal creatinine, higher TG, GPT and alcohol consumption.

The polymorphisms of Eotaxin 1 and CCR3 genes influence on serum IgE, Eotaxin levels and mild asthmatic children in Taiwan.

BACKGROUND: Asthma is a complex disorder, which is known to be affected by interactions between genetic and environmental factors. The human Eotaxin 1 and CCR3 attract eosinophils and Th2-lymphocytes to migrate to the inflammatory foci that could represent a key mechanism in allergy and asthma. OBJECTIVE: We hypothesized that Eotaxin1 gene Ala23Thr and A-384 G, and CCR3 gene T51C polymorphisms are associated with plasma Eotaxin levels and predispose individuals to asthma pathogenesis. METHODS: One hundred seventy-eight hospital-based asthmatic children and 277 community-based controls aged from 5 to 12 years were recruited in southern Taiwan. Whole blood samples and questionnaires were collected. In this study, we addressed genetic effects of Eotaxin 1 and CCR3 genes on asthma, plasma IgE and Eotaxin 1 levels. RESULTS: In comparison with subjects with Ala23Ala genotype, Ala23Thr polymorphism of the Eotaxin 1 gene showed a significant protective effect on asthma (AOR = 0.58, 95% CI = 0.37-0.92). We demonstrated that the mean Eotaxin 1 concentration was significantly higher in subjects with Ala23Ala than in subjects with Thr23Thr (P = 0.005) or Ala23Thr (P = 0.07), which showed a gene-dose dependent relationship. But, we observed that the A-384G polymorphism of Eotaxin 1 gene and T51C polymorphism of CCR3 gene are not associated with asthma. CONCLUSION: This study finding provide a strong evidence that Eotaxin 1 Thr23Thr homozygote has a protective effect on asthma and significantly decreases plasma Eotaxin 1 concentrations in asthmatics in Taiwan.

Ethnic differences in the occurrence of oropharyngeal cancer in Taiwan.

OBJECTIVE: The purpose of this study was to examine the oropharyngeal cancer pattern among different ethnic groups in Taiwan. METHODS: The sample population was divided into three ethnic groups: the Fukkien, Hakka, and aboriginal communities. Age-standardized mortality rates (SMRs) and age-standardized incidence rates (SIRs) were estimated among these ethnic groups for the period 1979-1996/1997. RESULTS: Our study found that the higher oropharyngeal cancer mortality and incidence rates in females of aboriginal groups are statistically significant, and higher than reference groups for both genders (SMR=3.76, SIR=2.18). However, in the lower areca quid chewing aboriginal groups, the higher pattern was not seen in females, and the lower pattern was even found in males. The incidence and mortality rate of oropharyngeal cancer in Hakkas was significantly lower than in the reference group. CONCLUSIONS: The pattern of oropharyngeal cancer in Taiwan showed ethnic differences. The differences may be due to variation in exposure to different risk factors; however, in our study, we found that genetic differences might also be considered when explaining the different oropharyngeal cancer patterns among ethnic groups.

UCP2 A55V variant is associated with obesity and related phenotypes in an aboriginal community in Taiwan.

OBJECTIVE: Human uncoupling proteins 2 and 3 (UCP2 and UCP3) are two mitochondrial proteins that are involved in the control of metabolism of fatty acid and possibly protect against oxidative damage. The aim of this study was to analyze genetic associations of four polymorphisms of the UCP2 and UCP3 genes with insulin, leptin concentration and obesity in Taiwan aborigines. RESEARCH METHODS: Four polymorphisms were compared in 324 obese (body mass index (BMI) > or =30 kg/m(2)) and overweight (30>BMI > or =25 kg/m(2)) subjects, and 114 normal weight subjects (BMI <25 kg/m(2)) in an aboriginal community of southern Taiwan. Anthropometric characteristics and fasting levels of insulin, leptin, triglycerides and cholesterol were measured. RESULTS: Before and after adjusting for age distribution, only the Val55 allele in exon 4 of the UCP2 gene increased the risk of overweight and obesity (adjusted odds ratio (OR)=2.02, P=0.004) in comparison with Ala55. UCP2 V55V is also associated with higher fasting insulin levels than A55V (P=0.01) and A55A (P=0.04) in the obese/overweight group. Using the COCAPHASE program of the UNPHASED software, haplotype analysis of three single nucleotide polymorphisms (A55V-G866A-C-55T) revealed that A-G-C (73% in obese subjects and 77% in controls) was the most common haplotype and that the haplotype V-A-T (13% in obese subjects and 5% in controls) was significantly increased in obese and overweight subjects (BMI > or =25 kg/m(2)) (OR=2.62, P<0.001). DISCUSSIONS: UCP2 A55V variant might predispose to obesity and Val55 allele to confer population-attributable risk for 9.5% of obese disorders and increase insulin concentrations. The V-A-T haplotype within UCP2-UCP3 gene cluster is also significantly associated with obesity in Paiwan aborigines.