Sequence Variants of Toll Like Receptor 4 and Late-Onset Alzheimer's Disease

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 (p(interaction) = 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

CHRNA7 Polymorphisms and Response to Cholinesterase Inhibitors in Alzheimer's Disease

Background: CHRNA7 encodes the alpha 7 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

Prospective study of effect modification by Toll-like receptor 4 variation on the association between Trichomonas vaginalis serostatus and prostate cancer

In previous studies, we observed a positive association between Trichomonas vaginalis serostatus and risk of prostate cancer, particularly aggressive cancer, which we hypothesized might be due to T. vaginalis-mediated intraprostatic inflammation and cell damage. To explore this hypothesis further, we investigated effect modification by Toll-like receptor 4 (TLR4) variation on this association. We hypothesized that TLR4 variation might serve a marker of the anti-trichomonad immune response because T. vaginalis has been shown to elicit inflammation through this receptor. We previously genotyped the non-synonymous TLR4 single nucleotide polymorphism (SNP), rs4986790, and determined T. vaginalis serostatus for 690 incident prostate cancer cases and 692 controls in a nested case-control study within the Health Professionals Follow-up Study. A non-significant suggestion of effect modification was observed by rs4986790 carrier status on the association between T. vaginalis serostatus and prostate cancer risk (p interaction = 0.07). While no association was observed among men homozygous wildtype for this SNP (odds ratio (OR) = 1.23, 95 % confidence interval (CI): 0.86-1.77), a positive association was observed among variant carriers (OR = 4.16, 95 % CI: 1.32-13.1). Although not statistically significant, TLR4 variation appeared to influence the association between T. vaginalis serostatus and prostate cancer risk consistent with the hypothesis that inflammation plays a role in this association. Larger studies will be necessary to explore this possible effect modification further

Obesity and the Occurrence of Bronchitis in Adolescents

Objective: Previous studies have shown that an elevated BMI was associated with higher risks of bronchitis among children. The magnitude of how increase in BMI influencing the risk of incident bronchitis remained unexplored. The objective of this study is to assess the association between BMI and the incidence of bronchitis in the Taiwan Children Health Study. Design: A school-based prospective cohort study. Methods: We conducted a population-based prospective cohort study among seventh-grade school children in 14 Taiwanese communities. A total of 3,634 adolescents completed follow-up questionnaire in 2009. Associations between BMI and incident bronchitis were analyzed by multiple Poisson regression models, taking overdispersion into account. Results: Among eligible cohort participants without bronchitis at study entry, the proportion of overweight and obesity were 32.1% and 17.9%. Overweight was 40.7% and obesity was 27.7% among those with incident bronchitis. The BMI percentile categories showed significant increasing trends for bronchitis in total eligible children and in girls (P for trend <0.001). Overweight and obesity were both associated with increased risks of incident bronchitis. This association was significant in girls only while stratified by gender. Conclusions: Our data showed that the BMI percentile and weight status were associated with higher risks of incident bronchitis in adolescents, especially in girls

Body Mass Index (Bmi) at an Early Age and the Risk of Dementia

BMI change and BMI at an early age have not been investigated as risks for dementia. This case-control study included 286 dementia patients and 268 controls from two medical centers between 2007 and 2009. BMI information was collected from medical records and questionnaires. Men and women with low BMIs at the time of the study, in their 20s, and in their 40s had significantly increased risks of Alzheimer's disease (AD) (odds ratio = OR = 2.62-3.97) and increased vascular dementia (VaD) risk (20s and 40s: OR = 6. 23-11.11) compared with those with normal BMIs. High BMI in the 20s and 40s was associated with increased VaD risk (OR = 15.29 and 10.32) among women. For BMI changes from the 20s or 40s, the second and third tertiles were significantly associated with decreased AD risk among women (OR = 0.15-0. 35) compared to the first tertile. The third tertile of BMI change from the 20s or 40s was associated with decreased VaD risk among women (OR = 0.06 and 0.14). Low BMIs in the 20s and 40s were stronger predictors of AD and VaD. There was a U-shaped association between BMI at different ages anddementia among participants with VaD

Early-Life or Lifetime Sun Exposure, Sun Reaction, and the Risk of Squamous Cell Carcinoma in an Asian Population

It has been widely accepted that sun exposure is a risk factor of squamous cell carcinoma (SCC) among fair-skinned populations. However, sun exposure and sun reaction have not been explored in Asians and no gender- specific data were available. In a case-control study, 176 incident skin cancer cases were recruited from National Cheng-Kung University Medical Center from 1996 to 1999. Controls included 216 age- , gender-, and residency-matched subjects from the southwestern Taiwan. A questionnaire was administered to collect information on life style and other risk factors. Logistic regression analysis was performed to evaluate the association between sun exposure or sun reaction and the risk of SCC by gender. Early-age (age 15 to 24) and lifetime sun exposure were significantly associated with increased risk of SCC in a dose-response pattern [odds ratio (OR) = 1. 49-3.08, trend p = 0.009 and 0.0007, respectively]. After stratified by gender, the third tertile of early-age sun exposure was significantly associated with the SCC risk among men (OR = 3.08). The second and third tertiles of lifetime sun exposure was significantly associated with SCC risk among women (OR = 3.78 and 4.53, respectively). Skin reaction after 2-h sun exposure during childhood and adolescence was not significantly associated with the risk of SCC. Lifetime sun exposure was more related to SCC risk in women, while early- age sun exposure was more relevant to men's SCC risk. This may be attributable to different lifestyle between men and women

Lung Adenocarcinoma and Human Papillomavirus Infection

Over the past three decades, the incidence of lung adenocarcinoma has increased worldwide. Most individuals with lung adenocarcinoma (especially women) are nonsmokers. Reported risk factors for the development of lung adenocarcinoma include cigarette smoking; exposure to cooking fumes, air pollution, second-hand smoke, asbestos, and radon; nutritional status; genetic susceptibility; immunologic dysfunction; tuberculosis infection; and asthma. Human papillomavirus (HPV) infection is a known risk factor for the development of squamous cell carcinoma (SCC), but it has not been thoroughly assessed as a potential risk factor for the development of pulmonary adenocarcinoma. More than 50% of people are infected with HPV during their lifetimes, either via intrauterine or postnatal infection. Recent studies involving Taiwanese patients have demonstrated a possible association between HPV infection and the risk of developing pulmonary adenocarcinoma. HPV transmission pathways have not yet been conclusively identified. The observation of certain types of HPV in association with cervical and oral SCC raises the possibility of sexual transmission of HPV from the cervix to the oral cavity, with subsequent transmission to the larynx and then to the lung. HPV infection and metaplasia in lung tissue may increase an individual's susceptibility to the tumorigenesis of pulmonary adenocarcinoma. Further epidemiologic and pathologic investigations will be necessary to establish a causal relation