Browsing by Author "Wen L.-L."

Acrylamide is present in mainstream cigarette smoke and in some foods prepared at high temperatures. Animal studies have shown that acrylamide exposure alters thyroid function; however, it is not known if this also occurs in humans. The study examined the association between the urinary levels of the acrylamide metabolite and serum thyroid measures in adolescents and young adults. We recruited 793 subjects (mean age, 21.3 years; range, 12-30 years) from a population-based sample of Taiwanese adolescents and young adults to determine if the urinary levels of the acrylamide metabolite N-acetyl-. S-(propionamide)-cysteine (AAMA) and the 6 serum thyroid measures are associated. The mean (SD) AAMA were 76.54 (76.42) μg/L. Linear regression analyzes showed a 1-unit increase in natural log AAMA was significantly associated with a decrease in serum free thyroxine (T4) (ng/dL) (. β=-0.041, SE=0.013, p=0.001) after controlling for covariates. Subpopulation analyzes showed AAMA and free T4 were significantly associated with females, age 20-30 years, non-current smokers, and non-alcohol consumers. In conclusion, higher urinary AAMA concentrations were associated with decreased levels of free T4 in this cohort. Further studies are warranted to determine if there is a causal relationship between acrylamide exposure and thyroid function. ? 2014 Elsevier Inc.

Context: Perfluorinated chemicals (PFCs) have been widely used in a variety of products worldwide for years. The relationship between serum PFCs and thyroid function has never been addressed in a nationally representative survey. Objectives: The study examined the association between serum PFCs and thyroid function in the general U.S. population. Design and Participants: We selected 1181 subjects (aged 20 years) from a National Health and NutritionExaminationSurvey(NHANES) in2007through2008and2009through2010todeterminethe relationship between serum PFCs and thyroid function. Data were adjusted for confounding variables. Results: The geometricmeansand95%confidence interval (CI) concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate, perfluorononanoic acid, and perfluorohexane sulfonate (PFHxS) were 4.15 (4.02- 4.29), 14.2 (13.59 -14.86), 1.54 (1.48 -1.59), and 2.00 (1.89 -2.11) ng/mL, respectively. After weighting for sampling strategy, we determined a 1-U increase in natural log-serumPFOAincreased serum total T3 concentration by 6.628 ng/dL (95% CI0.545-12.712, P .035) in women. A 1-U increase in natural log-PFHxS was associated with an increase of total T4 by 0.26 g/mL (95% CI 0.108-0.413, P .002) and total T3 by 4.074 ng/dL (95% CI 2.232-5.916, P.001) inwomenanda decrease of natural log-free T4 by 0.016 (ng/dL)(95%CI0.029 to 0.003, P .019) in men. Conclusion: Higher serum concentrations of PFOA and PFHxS are associated with total T3, total T4, and free T4 in the U.S. general population. More studies are warranted to clarify the causal relationship between PFCs and thyroid function. Copyright ? 2013 by The Endocrine Society.

In animals, perfluorinated chemicals (PFCs), specifically perfluorooctanoic acid (PFOA) and perfluorooctane sulfate (PFOS), function as peroxisome proliferator-activated receptor (PPAR) alpha agonists. However, the relevance of animal (primarily rodent) data to humans is unresolved. While plasma adiponectin level is very responsive to PPAR gamma agonist drugs, it has not been determined whether adiponectin level is related to serum PFCs concentrations. In the present study, 287 subjects (12-30 years of age) were recruited to determine the relationship between serum level of PFCs and serum level of adiponectin. The results showed males had higher serum PFOS concentrations than females and that those with metabolic syndrome had lower serum PFOA than controls. Besides, it showed regional elevations of the perfluoroundecanoic acid (PFUA) (median concentration: 7.11 ng/mL) in the study subjects. No relationship of PFOA, PFOS, PFUA, and the sum of all four PFCs was found to glucose homeostasis, adiponectin level, lipid profile, and inflammatory markers. The median and the range of perfluorononanoic acid (PFNA) concentration (in ng/mL; for four categories corresponding to the <50, 50-74, 75-89, and ?90th percentiles) were 0.38 (0.38-1.68), 3.22 (1.73-4.65), 5.85 (4.75-8.29), 10.56 (8.40-25.40), respectively. After controlling for confounding factors, multiple linear regression analysis revealed that the mean natural log-transformed level of adiponectin increased significantly across categories of PFNA (in ng/mL; 8.78, 8.73, 9.06, 9.36; P for trend = 0.010 in the full model). In conclusion, higher serum PFNA concentration is associated with elevated serum adiponectin concentration. ? 2011 American Chemical Society.

Perfluorinated chemicals (PFCs) have been widely used in a variety of products worldwide for years. However, the effect of PFCs on thyroid function has not yet been clearly defined. We recruited 567 subjects (aged 12-30 years) in a population-based cohort of adolescents and young adults with abnormal urinalysis in the childhood to determine the relationship between serum level of PFCs and the levels of serum free thyroxine (T4) and thyroid stimulating hormone (TSH). The geometric means and geometric standard deviation concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA) were 2.67 (2.96). ng/ml, 7.78 (2.42). ng/ml, 1.01 (3.48). ng/ml and 5.81 (2.92). ng/ml, respectively. Differences in the levels of free T4 and TSH across different categories of PFOA, PFOS and PFUA were insignificant. After controlling for confounding factors, multiple linear regression analyses revealed mean serum level of free T4 increased significantly across categories (<60th, 60-89 and >90th percentiles) of PFNA (P for trend =0.012 in the full model). The association between PFNA and free T4 was more significant in male subjects in age group 20-30, active smokers and in those with higher body mass index in stratified analysis. Serum concentrations of PFNA were associated with serum free T4 levels in adolescents and young adults. ? 2012 Elsevier B.V.

Background: CHRNA7 encodes the α7 nicotinic acetylcholine receptor subunit, which is important to Alzheimer's disease (AD) pathogenesis and cholinergic neurotransmission. Previously, CHRNA7 polymorphisms have not been related to cholinesterase inhibitors (ChEI) response. Methods: Mild to moderate AD patients received ChEIs were recruited from the neurology clinics of three teaching hospitals from 2007 to 2010 (n = 204). Nine haplotype-tagging single nucleotide polymorphisms of CHRNA7 were genotyped. Cognitive responders were those showing improvement in the Mini-Mental State Examination score ?2 between baseline and 6 months after ChEI treatment. Results: AD women carrying rs8024987 variants [GG+GC vs. CC: adjusted odds ratio (AOR) = 3.62, 95% confidence interval (CI) = 1.47-8.89] and GG haplotype in block1 (AOR = 3.34, 95% CI = 1.38-8.06) had significantly better response to ChEIs (false discovery rate <0.05). These variant carriers using galantamine were 11 times more likely to be responders than female non-carriers using donepezil or rivastigmine. Conclusion: For the first time, this study found a significant association between CHRNA7 polymorphisms and better ChEI response. If confirmed by further studies, CHRNA7 polymorphisms may aid in predicting ChEI response and refining treatment choice. ? 2013 Weng et al.

Background/purpose: Lipid metabolism is involved in beta amyloid generation, which has been related with the progression of Alzheimer's disease (AD). No study has explored the association between polymorphisms of SAR1 homolog B (SAR1B) and the risk of dementia previously. Methods: This is a case-control study. A total of 279 AD and 117 vascular dementia (VaD) patients were recruited from neurology clinics at three teaching hospitals in Taiwan from 2007 to 2010. Controls (n = 466) were recruited from the elderly health checkup program and volunteers in the hospital during the same time interval. Three common (frequency ? 5%) haplotype-tagging single nucleotide polymorphisms were selected from the lipid metabolism gene SAR1B to assess its association with AD and VaD. Results: Homozygous variants of rs11948613 were associated with a decreased AD risk (CC vs. TT: adjusted odds ratio = 0.39, 95% confidence interval = 0.15-0.98) with a population attributable risk of 26.7%. This association decreased further in apolipoprotein E ε4 (ApoE ε4) noncarriers (adjusted odds ratio = 0.28, 95% confidence interval = 0.09-0.91). No association was found for VaD. Two common haplotypes (with a cumulative frequency of 95.7% in controls) were identified for SAR1B, and no association was found for AD or VaD. Simultaneous screening using rs11948613 and ApoE ε4 significantly improved the sensitivity of ApoE ε4 alone (from 0.40 to 0.75). Conclusion: SAR1B polymorphisms were associated with AD risk; results were not significant after correction for multiple tests. Simultaneous screening using SAR1B rs11948613 and ApoE ε4 status offered a better sensitivity for AD screening. ? 2015.

Background: Loss of basal forebrain cholinergic neurons is attributable to the proapoptotic signaling induced by nerve growth factor receptor (NGFR) and may link to Alzheimer's disease (AD) risk. Only one study has investigated the association between NGFR polymorphisms and the risk of AD in an Italian population. Type 2 diabetes mellitus (DM) may modify this association based on previous animal and epidemiologic studies. Methods. This was a case-control study in a Chinese population. A total of 264 AD patients were recruited from three teaching hospitals between 2007 to 2010; 389 controls were recruited from elderly health checkup and volunteers of the hospital during the same period of time. Five common (frequency5%) haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected from NGFR to test the association between NGFR htSNPs and the risk of AD. Results: Variant NGFR rs734194 was significantly associated with a decreased risk of AD [GG vs. TT copies: adjusted odds ratio (OR) = 0.43, 95% confidence interval (CI) = 0.20-0.95]. Seven common haplotypes were identified. Minor haplotype GCGCG was significantly associated with a decreased risk of AD (2 vs. 0 copies: adjusted OR = 0.39, 95% CI = 0.17-0.91). Type 2 DM significantly modified the association between rs2072446, rs741072, and haplotype GCTTG and GTTCG on the risk of AD among ApoE 4 non-carriers (P interaction< 0.05). Conclusion: Inherited polymorphisms of NGFR were associated with the risk of AD; results were not significant after correction for multiple tests. This association was further modified by the status of type 2 DM. ? 2012 Cheng et al; licensee BioMed Central Ltd.

Background/Purpose: Leisure activities have been associated with a decreased risk of dementia. However, to date, no study has explored how apolipoprotein E (. ApoE) e4 status or vascular risk factors modified the association between leisure activities and dementia risks. Methods: This case-control study recruited patients (age ? 60 years) with Alzheimer's disease (AD; n = 292) and vascular dementia (VaD; n = 144) and healthy controls (. n = 506) from three teaching hospitals in Taiwan between 2007 and 2010. Information on patient's leisure activities were obtained through a questionnaire. Conditional logistic regression models were used to assess the association of leisure activities and ApoE e4 status with the risk of dementia. Results: High-frequency physical activity was associated with a decreased risk of AD [adjusted odds ratio (AOR) = 0.45], and the results become more evident among ApoE e4 carriers with AD (AOR = 0.30) and VaD (AOR = 0.26). Similar findings were observed for cognitive (AOR = 0.42) and social activities (AOR = 0.55) for AD. High-frequency physical, cognitive, and social activities were associated with a decreased risk of VaD (AOR = 0.29-0.60). Physical and social activities significantly interacted with each other on the risk of VaD (pinteraction = 0.04). Conclusion: Physical activity consistently protects against AD and VaD. Significant interactions were identified across different types of leisure activities in lowering dementia risk. ? 2014.

Context: Perfluorooctanoic acid (PFOA) and perfluorooctane sulfate (PFOS) are used in a variety of products worldwide. However, the relationship among serum PFOA, PFOS concentration, bone mineral density (BMD), and the risk of fractures has never been addressed. Objectives: The study examined the association among serum PFOA, PFOS concentration, and lumbar spine and total hip BMD in the general US population. Design and Participants: We analyzed data on 2339 adults (aged ?20 y) from the National Health and Nutrition Examination Survey conducted in 2005-2006 and 2007-2008 to determine the relationship among serum PFOA, PFOS concentration, and total lumbar spine and total hip BMD measured by dual-energy x-ray absorptiometry and history of fractures cross-sectionally. Results: After weighting for sampling strategy, a 1-U increase in the natural log-transformed serum PFOS level was associated with a decrease in total lumbar spine BMD by 0.022 g/cm2 (95% confidence interval -0.038, -0.007; P = .006) in women not in menopause. There was no association among PFOA, PFOS concentration, and self-reported fracture in adults. Conclusion: Serum PFOS concentration is associated with decreased total lumbar spine BMD in women not in menopause. However, the potential biological significance of this effect is marginal and subclinical in the general US population. Further studies are warranted to clarify the causal relationship between perfluorinated chemical exposure and BMD. ? 2014 by the Endocrine Society.

Acrylamide is present in mainstream cigarette smoke and in some foods prepared at high temperatures. Animal studies have shown that acrylamide exposure increases oxidative stress; however, it is not known if this also occurs in humans. We recruited 800 subjects (mean age, 21.3 years, range, 12-30 years) from a population-based sample of Taiwanese adolescents and young adults to determine if urinary levels of the acrylamide metabolite N-acetyl-S-(propionamide)-cysteine (AAMA) and the oxidative stress product 8-hydroxydeoxyguanosine (8-OHdG) are associated. The mean (SD) AAMA and 8-OHdG were 76.54 (76.42). μg/L and 3.48 (2.37). μg/L, respectively. In linear regression analyses, a 1-unit increase in natural log AAMA was significantly associated with an increase in natural log 8-OHdG (μg/g creatinine) (β=0.044, SE=0.019, P=0.020) after controlling for covariates. Subpopulation analyses showed AAMA and 8-OHdG were significantly associated with males, adolescents, non-current smokers, without alcohol consumption, subjects, body mass index ?24, and homeostasis model assessment of insulin resistance score ?0.9. In conclusion, higher urinary AAMA concentrations were associated with increased levels of urinary 8-OHdG in this cohort. Further studies are warranted to determine if there is a causal relationship between acrylamide exposure and oxidative stress. ? 2013 Elsevier B.V.

Introduction: Religious affiliations vary across ethnic groups because of different cultural backgrounds. Some studies have explored the association between religious affiliation and cognitive decline. Only a small portion of patients with cognitive decline progress to dementia. However, the association between religious affiliation and dementia risk remains unclear. Methods: In this case-control study, we recruited 280 patients with Alzheimer's disease (AD) and 138 with vascular dementia (VaD) (both aged ?60 years) from three teaching hospitals in northern Taiwan between 2007 and 2010. Age-matched healthy controls (. n=. 466) were recruited from an elderly health checkup program and from volunteers visiting the hospital during the same period. Three religious affiliations-Taoism, Buddhism, and Christianity-were evaluated. The study also assessed the effect of important factors such as gender or leisure activities on the association of religious affiliation with dementia risk. Results: Participants with Christianity affiliation showed decreased AD risk (adjusted odds ratio [AOR]. =. 0.46, 95% confidence interval [CI]. =. 0.25-0.87) compared with those without any religious affiliation. Moreover, this effect was stronger in women (AOR. =. 0.38, 95% CI. =. 0.15-0.92) and in participants who exercised regularly (>3 times/week; AOR. =. 0.33, 95% CI. =. 0.14-0.77). No significant association was observed among participants with Taoism and Buddhism affiliations. Affiliation to none of the religions was associated with VaD risk. Conclusions: Thus, Chinese participants having Christianity affiliation showed decreased AD risk. Moreover, the protective effect was more evident in women and in participants who exercised regularly. ? 2015 Elsevier Ireland Ltd.

Background: Toll like receptor 4 (TLR4) has been related to inflammation and beta-amyloid deposition in Alzheimer's disease (AD) brain. No study has explored the association between haplotype-tagging single nucleotide polymorphisms (htSNPs) of TLR4 and AD risk previously and ApoE e4 status alone showed low sensitivity in identifying late-onset AD (LOAD) patients. Methods: A total of 269 LOAD patients were recruited from three hospitals in northern Taiwan (2007-2010). Controls (n = 449) were recruited from elderly health checkup and volunteers of the hospital during the same period of time. Five common (frequency?5%) TLR4 htSNPs were selected to assess the association between TLR4 polymorphisms and the risk of LOAD in the Chinese ethnic population. Results: Homozygosity of TLR4 rs1927907 was significantly associated with an increased risk of LOAD [TT vs. CC: adjusted odds ratio (AOR) = 2.45, 95% confidence interval (CI) = 1.30-4.64]. After stratification, the association increased further in ApoE e4 non-carriers (AOR = 3.07) and in hypertensive patients (AOR = 3.60). Haplotype GACGG was associated with a decreased risk of LOAD (1 vs. 0 copies: AOR = 0.59, 95% CI = 0.36-0.96; 2 vs. 0 copies: AOR = 0.31, 95% CI = 0.14-0.67) in ApoE e4 non-carriers. ApoE e4 status significantly modified this association (pinteraction = 0.01). These associations remained significant after correction for multiple tests. Conclusions: Sequence variants of TLR4 were associated with an increased risk of LOAD, especially in ApoE e4 non-carriers and in hypertensive patients. The combination of TLR4 rs1927907 and ApoE e4 significantly increased the screening sensitivity in identifying LOAD patients from 0.4 to 0.7. ? 2012 Chen et al.