Characteristics of the study population.

<p><b>Abbreviations:</b> BMD, bone mineral density; BMI, body mass index; hypertension, systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg or had medication for controlling blood pressure; diabetes, fasting glucose ≥126 mg/dl or using medication for diabetes; regular exercise: walking or hiking ≥30 mins/2 to 3 days.</p><p>Numbers in bold indicate significant findings (<i>p</i><0.05).</p

Association of <i>SPP1</i> common htSNPs and haplotypes with low BMD.

<p><b>Abbreviations:</b> SNP, single nucleotide polymorphism; Freq., haplotype frequency; BMD, bone mineral density; AOR, adjusted odds ratio; CI, confidence interval; L, low BMD; H, high BMD.</p><p>All models were adjusted for age, menopausal status, BMI (kg/m²), serum ALP (IU/L), UA (mg/dL), LDL (mg/dL), and exercise (frequency × duration × intensity).</p><p>The SNPs with underscore indicate variant allele.</p><p>Numbers in bold indicated significant findings (<i>p</i><0.05).</p

<i>CHRNA7</i> Polymorphisms and Response to Cholinesterase Inhibitors in Alzheimer's Disease

<div><p>Background</p><p><i>CHRNA7</i> encodes the α7 nicotinic acetylcholine receptor subunit, which is important to Alzheimer's disease (AD) pathogenesis and cholinergic neurotransmission. Previously, <i>CHRNA7</i> polymorphisms have not been related to cholinesterase inhibitors (ChEI) response.</p><p>Methods</p><p>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 <i>CHRNA7</i> were genotyped. Cognitive responders were those showing improvement in the Mini-Mental State Examination score ≧2 between baseline and 6 months after ChEI treatment.</p><p>Results</p><p>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<b>.</b></p><p>Conclusion</p><p>For the first time, this study found a significant association between <i>CHRNA7</i> polymorphisms and better ChEI response. If confirmed by further studies, <i>CHRNA7</i> polymorphisms may aid in predicting ChEI response and refining treatment choice.</p></div

<i>CHRNA7</i> linkage disequilibrium (LD) plot.

<p>The plot was generated by applying the Haploview program to genotype data from this study. The level of pairwise D', which indicates the degree of LD between two SNPs, is shown in the LD structure in gray scale. The level of pairwise r², which indicates the degree of correlation between two SNPs, is indicated by the number in the cell. Different numbers of common (frequency ≥5%) haplotypes were identified in each haplotype block. A modified Gabriel et al. algorithm was used to define the haplotype block <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084059#pone.0084059-Gabriel1" target="_blank">[32]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084059#pone.0084059-Chen1" target="_blank">[33]</a>.</p

Postulated mechanism for <i>CHRNA7</i> polymorphisms and ChEI cognitive response.

<p>ChEIs increase the level of acetylcholine, which binds to α7 nAChR (encoded by <i>CHRNA7</i>). <i>CHRNA7</i> polymorphisms are postulated to affect the cognitive response to ChEIs through the following mechanisms: (1) modulation of neurotransmitter release in presynaptic neurons, (2) enhancement of memory via mediating cholinergic neurotransmission, (3) neuroprotection via α7 nAChR, (4) upregulation of α7 nAChR by ChEI, and (5) galantamine-associated positive allosteric modulation of α7 nAChR. Abbreviations: nAChR, nicotinic acetylcholine receptor; ACh, acetylcholine; ChE, cholinesterase; ChEI, cholinesterase inhibitor.</p

Characteristics of <i>CHRNA7</i> haplotype-tagging SNPs.

<p>Abbreviations: SNP, single nucleotide polymorphism; MAF, minor allele frequency; HWE, Hardy–Weinberg equilibrium test.</p

<i>CHRNA7</i> SNP2 (rs8027987) and ChEI response by sex and ChEI type.

<p>Abbreviations: SNP, single nucleotide polymorphism; ChEI, cholinesterase inhibitor; AOR, adjusted odds ratio; CI, confidence interval.</p><p>Non-galantamine refers to users of donepezil or rivastigmine.</p><p><i>P</i><0.05, ^**<i>P</i><0.01.</p><p>All models were adjusted for age, baseline MMSE, hypertension, <i>and APOE</i> ε4 status.</p

Baseline characteristics and ChEI types of the study population.

<p>Abbreviations: SD, standard deviation; MMSE, Mini-Mental State Examination; <i>APOE</i>, apolipoprotein E; ChEI, cholinesterase inhibitor.</p><p><i>P</i><0.01 for comparing responders to non-responders.</p

Descriptive statistics of the lifestyle factors and their cut-off points.

<p>Descriptive statistics of the lifestyle factors and their cut-off points.</p

Adjusted effects of individual lifestyle factors and SES indicators on cognitive change.

<p>Adjusted effects of individual lifestyle factors and SES indicators on cognitive change.</p