A randomized, parallel control and multicenter clinical trial of evidence-based traditional Chinese medicine massage treatment VS External Diclofenac Diethylamine Emulgel for the treatment of knee osteoarthritis.

BACKGROUND: Both massage and topically administered NSAIDs are safe and effective treatments for knee osteoarthritis (KOA); however, different massage technique sects in China caused assessment difficulties for the treatment of KOA. In order to standardize the massage techniques and procedures, we organized multi-disciplinary experts in China to acquire an evidence-based traditional Chinese medicine massage treatment of knee osteoarthritis. The purposes of this study will be to provide clinicians a complementary and alternative therapy for patients and to evaluate the efficacy and safety of evidence-based traditional Chinese medicine massage treatment of KOA compared to External Diclofenac Diethylamine Emulgel. METHODS AND DESIGN: A randomized controlled trial in which 300 participants diagnosed with KOA will be recruited and randomly allocated to either the experimental group or the control group in a ratio of 2:1. Two hundred participants will receive evidence-based traditional Chinese medicine massage 2 sessions per week for 10 weeks as the experimental group, and 100 participants will receive External Diclofenac Diethylamine Emulgel 3-4 times per day for 10 weeks as the control group. The patients in the two groups will receive follow-up at two time points at 5 weeks and 10 weeks from the beginning of treatment, respectively. The MRI scans and X-ray will be performed at baseline and at the end of the intervention. The primary outcome will be the changes in the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Secondary outcomes will be measured by the PRO scale for knee osteoarthritis based on the concept of traditional Chinese medicine (Chinese scale for knee osteoarthritis (CSKO)), X-ray evaluation, and MRI scan evaluation. The data of WOMAC and CSKO will be analyzed at the baseline, 5 weeks, and 10 weeks from the beginning of treatment. The data from MRI scans and X-rays will be analyzed at baseline and at the end of the intervention. The significance level sets as 5%. The safety of interventions will be evaluated after each treatment session. DISCUSSION: This study will provide clinicians with much-needed knowledge for the treatment of KOA through a controlled trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800014400 . Registered on 10 January 2018.

Activation of adenosine receptor potentiates the anticonvulsant effect of phenytoin against amygdala kindled seizures.

Drug resistance in epilepsy is considered as a complicated and multifactorial problem. Poor penetration of antiepileptic drugs (AEDs) across blood-brain barrier (BBB) into the brain, which results in insufficient level of the drugs at the targeted brain region, has been discussed as one mechanism contributing to pharmacoresistance of epilepsies. Therefore, modulating permeability of BBB is the effective treatment strategy since it facilitates the entry of AEDs into the central nervous system (CNS). Recently, signaling through receptors for the adenosine has been identified as a potent modulator of BBB permeability. This paper aimed to investigate the effects of auxiliary application of adenosine receptor (AR) agonist on amygdala-kindled seizures in adult male Wistar rats. When fully kindled seizures were achieved by daily electrical stimulation of the amygdala, rats were randomly divided into three groups: control, phenytoin, and phenytoin (PHT)+5'-N-ethylcarboxamidoadenosine (NECA) groups. NECA (0.08 mg/kg, i.v.) was applied to the PHT+NECA group after the administration of PHT (75 mg/kg, i.p. on the first day; 50mg/kg, i.p. on the following 9 days). Intravenous infusion of NECA resulted in a significant increase in brain PHT levels as compared with the PHT treatment alone. On the other hand, the auxiliary application of NECA dramatically decreased the frequency of generalized seizures and seizure stage, shortened duration of afterdischarge and generalized seizures, as well as the elevated the afterdischarge threshold and generalized seizures threshold. Our study demonstrated that auxiliary application of AR agonist enhanced brain antiepileptic drug levels and strengthened the anticonvulsant properties of PHT against amygdala kindled seizures.

Targeting the mTOR signaling network for Alzheimer's disease therapy.

The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that can sense environmental stimuli such as growth factors, energy state, and nutrients. It is essential for cell growth, proliferation, and metabolism, but dysregulation of mTOR signaling pathway is also associated with a number of human diseases. Encouraging data from experiments have provided sufficient evidence for the relationship between the mTOR signaling pathway and Alzheimer's disease (AD). Upregulation of mTOR signaling pathway is thought to play an important role in major pathological processes of AD. The mTOR inhibitors such as rapamycin have been proven to ameliorate the AD-like pathology and cognitive deficits effectively in a broad range of animal models. Application of mTOR inhibitors indicates the potential value of reducing mTOR activity as an innovative therapeutic strategy for AD. In this review, we will focus on the recent process in understanding mTOR signaling pathway and the vital involvement of this signaling pathway in the pathology of AD, and discuss the application of mTOR inhibitors as potential therapeutic agents for the treatment of AD.

Association of GWAS-linked loci with late-onset Alzheimer's disease in a northern Han Chinese population.

OBJECTIVE: Five genomewide association studies (GWAS) in white populations have recently identified and confirmed 9 novel Alzheimer's disease (AD) susceptibility loci (CLU, CR1, PICALM, BIN1, ABCA7, MS4A gene cluster, CD2AP, CD33, and EPHA1). These studies have been conducted almost exclusively in white populations and it is unclear whether these observations generalize to populations with different ethnicities. METHODS: We recruited 1224 unrelated northern Han Chinese subjects comprising 612 patients with a clinical diagnosis of late-onset AD (LOAD) according to the criteria of the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association and 612 healthy age- and sex-matched control subjects. Because of our previous study investigating CLU, CR1, and PICALM in the Han population, we limited the current analysis to BIN1, ABCA7, MS4A gene cluster, CD2AP, CD33, and EPHA1. RESULTS: In a multivariate analysis, associations of MS4A6A (rs610932; odds ratio = 0.632, Bonferroni corrected P = .019) and CD33 (rs3865444; odds ratio = 1.492, Bonferroni corrected P = .017) with LOAD were replicated successfully. When these data were stratified by apolipoprotein E (APOE) ε4 status, both rs610932 and rs610932 were evident only among subjects without the APOE ε4 allele. For BIN1, assuming a dominant model of inheritance, a positive association for rs7561528 in APOE ε4 carriers was observed. This association, however, did not remain significant after Bonferroni correction. As for ABCA7, CD2AP, and EPHA1 single nucleotide polymorphisms from recent GWAS, despite the similar directional effects, no significant differences in genotype and estimated allele frequency distribution between patients and control subjects were observed. CONCLUSIONS: This study provides the first independent evidence that MS4A and CD33 loci are associated with the risk of LOAD in northern Han Chinese population. Genotypes at the two loci confer risk predominantly in APOE ε4-negative subjects.

Clusterin in Alzheimer's disease.

Clusterin, also known as apolipoprotein J, is a ubiquitous multifunctional glycoprotein. Following its identification in 1983, clusterin was found to be clearly increased in Alzheimer's disease (AD). Later research demonstrated that clusterin could bind amyloid-beta (Abeta) peptides and prevent fibril formation, a hallmark of AD pathology. In addition to preventing excessive inflammation, intracellular clusterin was found to reduce apoptosis and oxidative stress. Although early studies were inconclusive, two recent large-scale genome-wide association studies (GWAS) independently identified variants within the clusterin gene as risk factors for developing AD. This review focuses on the characteristics of clusterin and possible mechanisms of its relationship to AD.

Genetic association of SLC2A14 polymorphism with Alzheimer's disease in a Han Chinese population.

Glucose uptake and metabolism are impaired in Alzheimer's disease (AD) brain, which appear to be a cause, rather than a consequence of neurodegeneration. Recently, the gene of the 14th isoform of subfamily A of solute carrier family 2 (SLC2A14), encoding glucose transporter 14 (GLUT14), was identified for the association in vivo with AD pathology of Tau, and rs10845990 within SLC2A14 showed association with AD in Caucasians. In order to evaluate the involvement of the SLC2A14 polymorphism in the risk of developing late-onset Alzheimer's disease (LOAD) in Chinese, we performed an independent case-control association study in a Han Chinese population (597 LOAD cases and 605 healthy controls). There were significant differences in genotype and allele frequencies between LOAD cases and controls (genotype P = 0.015, allele P = 0.039). The G-carrying genotype (GT + GG) individuals showed a 1.41-fold increased risk compared with the TT genotype carriers (odds ratio (OR) = 1.41, 95 % confidence interval (CI) = 1.11-1.79, P = 0.005, Power = 83.6 %). After stratification by ApoE ε4-carrying status, rs10845990 polymorphism was only significantly associated with LOAD in non-ApoE ε4 allele carriers (P < 0.001). Multivariate logistic regression analysis also conferred this positive association between the SNP rs10845990 and LOAD in the dominant and additive model after adjustment for age, gender, and the ApoE ε4 carrier status. These results suggested that SLC2A14 polymorphism has a possible role in changing the genetic susceptibility to LOAD in a Han Chinese population.

Lack of association between rs597668 polymorphism near EXOC3L2 and late-onset Alzheimer's disease in Han Chinese.

Recently, an international genome-wide association study (GWAS) additionally found rs597668 near EXOC3L2/BLOC1S3/MARK4 was a new genome-wide significance locus associated with late-onset Alzheimer's disease (LOAD) in Caucasians. Follow-up replication studies were conducted almost exclusively in Caucasians, and the effects of the risk locus in other populations are as yet unknown. This study investigated the GWAS-associated locus near EXOC3L2 in 1205 unrelated Northern Han Chinese subjects comprising 598 LOAD patients and 607 healthy controls matched for gender and age. The results showed no significant differences in the genotypic or allelic distributions of rs597668 polymorphism between LOAD cases and healthy controls (genotype: P=0.653; allele: P=0.603), even after stratification for apolipoprotein E (APOE) ɛ4 status and statistical adjustment for age, gender and APOE ɛ4 status. This study suggests that the rs597668 polymorphism near EXOC3L2 may not play a major role in the susceptibility to LOAD in the Northern Han Chinese population.

Replication of the MTHFD1L gene association with late-onset Alzheimer's disease in a Northern Han Chinese population.

We conducted a replication study of the 2 genetic variants, rs11754661 and rs2073067, in MTHFD1L that have been recently reported to be associated with late-onset Alzheimer's disease (LOAD) in a genome-wide study in Caucasians. The associations were evaluated in a case-control sample comprising 1,189 Northern Han-Chinese individuals. The rs11754661 polymorphism is associated with LOAD (OR = 1.727; p = 0.016). For rs2073067, LOAD association was found only in APOEε4 carriers (OR = 0.400; p < 0.001). Haplotype analysis revealed the "AC" haplotype increased the risk of developing LOAD (OR = 1.730; p = 0.015). Our findings support a role of MTHFD1L gene in LOAD.

Blood clusterin levels, rs9331888 polymorphism, and the risk of Alzheimer's disease.

Variants in the clusterin gene have been associated with Alzheimer's disease (AD) through replicated genome-wide studies, but the underlying mechanisms remain unknown. In this study the association of the AD clusterin common risk polymorphism rs9331888 with blood clusterin levels was tested in 104 AD subjects and 104 healthy controls. Blood clusterin levels were significantly elevated in AD patients (p < 0.05). The rs9331888 AD-risk variant was associated with low clusterin mRNA and protein levels in an allele-dose dependent manner in both groups (p < 0.001). This study indicates that the rs9331888 AD-risk variant is associated with low blood clusterin levels.

Common variants in toll-like receptor 4 confer susceptibility to Alzheimer's disease in a Han Chinese population.

Toll-like receptor 4 (TLR4) represents a reasonable functional and positional candidate gene for Alzheimer's disease (AD) as it is located within the previous identified linkage region of AD on chromosome 9q, and functionally is involved in the microglia-mediated inflammatory response, amyloid-ß (Aß) plaque formation and Aß clearance. To test whether variants in the TLR4 gene are associated with late-onset AD (LOAD), we organized a multicenter study of 785 subjects (399 cases and 386 matched controls) in a Han Chinese population. Ten single nucleotide polymorphisms (SNPs) that span the TLR4 gene, from approximately 5 kb of the predicted 5'-untranslated region (UTR) to approximately 6 kb of the predicted 3'- UTR, were selected and their associations with LOAD risk factors were assessed. With respect to allelic diversity, the minor alleles of seven SNPs (rs10759930, rs1927914, rs1927911, rs12377632, rs2149356, rs7037117, and rs7045953) in TLR4 showed consistent protective effects against the risk of developing LOAD. With regard to genotypic diversity, individuals carrying at least one minor allele of each SNP above had a consistently lower risk of LOAD than those with no copies of the minor alleles (ORs ranging from 0.445 to 0.637). rs7045953, located in the 3'-UTR of TLR4, was most strongly associated with LOAD, and when incorporated into a haplotype with rs10759930, the strongest association was detected (P = 1.7x10-6, Pc s1.0x10-4). Our data suggests that the TLR4 gene contributes to the susceptibility for LOAD in Han Chinese.

Implication of IL-33 gene polymorphism in Chinese patients with Alzheimer's disease.

Interleukin-33 (IL-33), a newly described member of the IL-1 family, is located on chromosome 9p24, a chromosomal region of interest in Alzheimer's disease (AD) defined by many genome-wide studies. Three intronic rs1157505, rs11792633, and rs7044343 single nucleotide polymorphisms (SNPs) within IL-33 have recently been reported to be associated with risk of AD in Caucasian populations. In order to assess the involvement of the IL-33 polymorphisms in the risk of developing late onset AD (LOAD), we analyzed the genotype and allele distributions of these 3 polymorphisms in 704 Han Chinese subjects. The minor alleles of the rs11792633 polymorphism within IL-33 was significantly associated with a reduced risk of LOAD (odds ratio [OR] = 0.73, p = 0.005). Furthermore, rs11792633 polymorphism was still strongly associated with LOAD (dominant model: OR = 0.67, p = 0.015; recessive model: OR 0.57, p = 0.021; additive model: OR = 0.71, p = 0.004) after adjusting for age, gender, and the apolipoprotein E (APOE) ε4 status. Our results support the evidence that genetic variants of IL-33 affect susceptibility to LOAD in Han Chinese.

Anticonvulsant effect of unilateral anterior thalamic high frequency electrical stimulation on amygdala-kindled seizures in rat.

Deep brain stimulation (DBS) is an emerging treatment of epilepsy. Anterior nucleus of the thalamus (ANT) is considered to be an attractive target due to its close connection to the limbic structures and wide regions of neocortex. In this study, we examined the effect of unilateral high frequency stimulation (HFS) of the ANT on amygdala-kindled seizures in Wistar rats. When fully-kindled seizures were achieved by daily amygdala kindling, HFS (15 min train of 100 µs pulses at 200 Hz and 450-800 µA) was delivered to the ipsilateral or contralateral ANT immediately before the kindling stimulation for 15 days. HFS of the ipsilateral ANT significantly decreased the incidence of generalized seizures and the mean behavioral seizure stage and afterdischarge duration (ADD), and shortened cumulative ADD and cumulative generalized seizure duration. Furthermore, HFS of the ipsilateral ANT significantly increased the afterdischarge threshold (ADT). Our data suggest that unilateral HFS of the ANT may be an effective method of inhibiting kindled seizures by suppressing the susceptibility to seizures and generating long lasting anti-epileptic effect preventing the recurrence of kindled seizures, providing an alternative to bilateral ANT DBS for refractory epilepsy.

[The evaluation of hydrocarbon potential generation for source rocks by near-infrared diffuse reflection spectra].

Near-infrared (NIR) and mid-infrared (MIR) diffuse reflection spectra were compared and evaluated for hydrocarbon potential generation of source rocks. Near-infrared diffuse reflectance often exhibits significant differences in the spectra due to the non-homogeneous distribution of the particles, so the signal-to-noise ratio of NIR is much lower than MIR It is too difficult to get accurate results by NIR without using a strong spectral preprocessing method to remove systematic noise such as base-line variation and multiplicative scatter effects. In the present paper, orthogonal signal correction (OSC) and an improved algorithm of it, i.e. direct orthogonal signal correction (DOSC), are used as different methods to preprocess both the NIR and MIR spectra of the hydrocarbon source rocks. Another algorithm, wavelet multi-scale direct orthogonal signal correction (WMDOSC), which is a combination of discrete wavelet transform (DWT) and DOSC, is also used as a preprocessing method. Then, the calibration model of hydrocarbon source rocks before and after pretreatment was established by interval partial least square (iPLS). The experimental results show that WMDOSC is more successfully applied to preprocess the NIR spectra data of the hydrocarbon source rocks than other two algorithms, and NIR performed as good as MIR in the analysis of hydrocarbon potential generation of source rocks with WMDOSC-iPLS pretreatment calibration model.

Genetic association of TLR4/11367 polymorphism with late-onset Alzheimer's disease in a Han Chinese population.

The amyloid beta-protein (A-ß) deposits in the brains of patients with Alzheimer's disease (AD) are closely associated with innate immune responses that were assumed to play a pivotal role in the pathogenesis of AD. Toll-like receptor 4 (TLR4) is thought to contribute to Aß clearance. Studies have reported the presence and functional significance of the TLR4/11367 polymorphism in a Han Chinese population. To evaluate the involvement of the TLR4/11367 polymorphism in the risk of late-onset Alzheimer's disease (LOAD), we performed a case-control study to analyze the genotype and allele distributions of the TLR4/11367 polymorphism in a Han Chinese population (137 LOAD cases and 137 healthy controls). There were significant differences in genotype and allele frequencies between LOAD cases and controls (genotype P<0.001, allele P<0.001). After stratification by APOE ε4-carrying status, the C allele of the TLR4/11367 polymorphism was still significantly associated with LOAD in APOE ε4 non-carriers (OR=5.77, 95% CI=3.03-11.00, P<0.001) and carriers (OR=2.03, 95% CI=1.03-3.98, P=0.04). In addition, a logistic regression analysis also conferred positive association between TLR4/11367C and LOAD (dominant model: ORa=3.08, 95% CI=1.60-5.93, P=0.001; recessive model: ORa=8.79, 95% CI=3.31-23.36, P<0.001; additive model: ORa=2.75, 95% CI=1.73-4.37, P<0.001) after adjustment for age, gender, and the APOE ε4 carrier status. This study gives the first evidence that the TLR4/11367 polymorphism was associated with LOAD in a Han Chinese population.

Genetic association of rs11610206 SNP on chromosome 12q13 with late-onset Alzheimer's disease in a Han Chinese population.

BACKGROUND: Several genome wide screens and candidate gene studies have implicated the chromosome 12p13 locus as possibly harboring genetic variants predisposed to late-onset Alzheimer's disease (LOAD). Recently, the strongest significant association was reported for the single nucleotide polymorphism (SNP) rs11610206 on chromosome 12q13 in an independent genome-wide association study (GWAS) in Caucasians. METHODS: We investigated whether the SNP on chromosome 12q13 was associated with LOAD in a Han Chinese population. The common rs11610206 SNP on chromosome 12q13 was genotyped using MALDI-TOF mass spectrometry in 322 patients with LOAD and in 391 healthy controls matched for sex and age. RESULTS: Patients with LOAD had higher frequencies of T allele (56.0% versus 49.2%) compared with controls [odds ratio (OR)=1.45, 95% confidence intervals (CI)=1.08-1.95, and P=0.01]. After stratification by APOE ε4-carrying status, the T allele of rs11610206 was significantly associated with LOAD only in APOE ε4 allele carriers (OR=2.05, 95% CI=1.21-3.47, and P=0.007). Furthermore, multivariate logistic regression analysis showed that the TT genotype carriers demonstrated a 1.52-fold risk when compared with (TC+CC) genotype carriers (OR=1.52, 95% CI=1.07-2.17, and P=0.02). CONCLUSIONS: This study demonstrates an association of rs11610206 polymorphism locus on chromosome 12q13 with risk for LOAD in Han Chinese.

Mitochondrial transcription factor A (TFAM) polymorphisms and risk of late-onset Alzheimer's disease in Han Chinese.

Chronic mitochondria DNA (mtDNA) damage and mitochondrial dysfunction induced by increased reactive oxygen species (ROS) have been proved to contribute to the development of Alzheimer's disease (AD). Mitochondrial transcription factor A (TFAM) plays an important role in the maintenance of mtDNA integrity. Recently, some studies suggested two single nucleotide polymorphisms (SNPs) (rs1937 and rs2306604) in the TFAM gene are associated with sporadic late-onset AD (LOAD) in Caucasians. To explore the correlation between TFAM gene and LOAD, we performed a case-control study in a large Chinese cohort consisting of 394 patients and 390 healthy controls. The results showed that there were significant differences in genotype (P=0.03) and allele (P=0.04) frequencies of the SNP rs1937 between LOAD patients and controls. The minor C allele of rs1937 acted as a moderate protective factor of LOAD (P=0.04, odds ratios/OR=0.76). The logistic regression analysis also suggested an association of LOAD with SNP rs1937 (dominant model: P=0.03, OR=0.71; recessive model: P=0.02, OR=0.25; additive model: P=0.01, OR=0.68). No significant association was observed between rs2306604 and LOAD. Haplotype analysis identified the haplotype CC as a protective factor of LOAD (P=0.038, OR=0.76). This study provides the evidence that variations in TFAM are involved in the pathogenesis of sporadic LOAD in the Han Chinese population.

Association of DAPK1 genetic variations with Alzheimer's disease in Han Chinese.

Apoptosis and autophagy are common physiological and pathological processes in the human body. Death-associated kinase protein 1 (DAPK1), which participates in the process of cell death, has attracted people's attention for its potential risk with late-onset Alzheimer's disease (LOAD). A recent study identified two single nucleotide polymorphisms (SNPs) in DAPK1 that show significant association with LOAD in Caucasians. In order to clarify the role of these genetic variations in Chinese population, we examined the genetic variations of DAPK1/rs4877365 and DAPK1/rs4878104 in a group of 400 LOAD patients and 400 healthy controls. All samples were recruited from Northern Han Chinese population. Data collected from this study showed that there were significant differences in genotype (P=0.02) and allele (P=0.007) frequencies of DAPK1/rs4878104 but not in DAPK1/rs4877365 between LOAD patients and controls. The "C" allele of rs4878104 worked as a protective factor of LOAD (P=0.0026, odds ratio/OR=0.75) in Han Chinese. Logistic regression analysis revealed that homozygosity was strongly associated with LOAD under a recessive model (P=0.003, OR=0.23). No significant association was observed between rs4877365 and LOAD. Haplotype analysis identified the G/T haplotype as a risk factor for LOAD (P=0.007, OR=1.33, 95% CI=1.08-1.64). This study provides the evidence that variation in DAPK1 gene influences susceptibility to LOAD in the Northern Han Chinese population.

Association between late-onset Alzheimer's disease and microsatellite polymorphisms in intron II of the human toll-like receptor 2 gene.

The amyloid beta protein (Aß) deposits in the brains of patients with Alzheimer's disease (AD) are closely associated with innate immune responses that were assumed to play a pivotal role in the pathogenesis of AD. Toll-like receptor 2 (TLR2) is thought to contribute to Aß clearance. Studies have reported the presence and functional implications of guanine-thymine (GT) repeat microsatellite polymorphisms in intron II of the human TLR2 gene. The present study evaluated the association of the microsatellite polymorphism and sporadic late-onset AD (LOAD) in the Han Chinese population. The numbers of (GT) repeats were counted in 137 AD patients and in 137 non-AD control subjects, using polymerase chain reaction and genescan analysis. The alleles were divided into three subclasses: (GT)16 or less as the S allele, (GT)17 to (GT)22 as the M allele, and (GT)23 or more as the L allele. Patients with AD had more S alleles (P<0.001; odds ratio (OR)=2.32; 95% confidence interval (CI)=1.57-3.42) and fewer L alleles (P=0.02; OR=0.66; 95% CI=0.46-0.93) than did healthy controls. Genotypes SS and SM were more common, whereas ML and SL were less common in patients with AD. In subgroup analyses, the genotypes including S alleles were associated with an increased risk of LOAD (OR=2.05, 95% CI=1.26-3.34), and this association was influenced by the presence of APOE ɛ4 alleles. This study demonstrates an association of microsatellite polymorphisms in intron II of the human TLR2 gene with risk for LOAD in Han Chinese.

Lack of association between PCDH11X genetic variation and late-onset Alzheimer's disease in a Han Chinese population.

Protocadherin 11X (Pcdh11X) has been suspected to be associated with Alzheimer's disease through participating in the metabolism of PP1α and ß-catenin or by altering the synaptic functions. A recent genome-wide association study reported that a common single nucleotide polymorphism (SNP, rs5984894) in the gene encoding Pcdh11X was associated with susceptibility to late-onset Alzheimer's disease (LOAD) in Caucasians. In order to assess the involvement of the PCDH11X polymorphism in the risk of developing AD in Chinese, we analyzed the genotype and allele distributions of the PCDH11X rs5984894 polymorphism in a Han Chinese population (355 LOAD cases and 399 healthy controls). Our results failed to find any significant association between the tested SNP and LOAD, indicating that PCDH11X gene polymorphism does not play a major role in the genetic predisposition to LOAD in this Han Chinese population.

Implication of CLU gene polymorphisms in Chinese patients with Alzheimer's disease.

BACKGROUND: Clusterin (also called apolipoprotein J) has a potential central role in the pathogenesis of Alzheimer's disease (AD). Recently, two genome-wide association studies have identified three variants in CLU gene encoding clusterin associated with AD risk in Caucasians, while there are no studies on the association of CLU with AD risk in Asians. METHODS: The study investigated 324 sporadic late-onset AD (LOAD) and 388 healthy controls matched for sex and age in a Han Chinese population. Three common genetic variants (rs2279590, rs11136000 and rs9331888) in CLU gene were genotyped using MALDI-TOF mass spectrometry. RESULTS: The minor allele (G) of the rs9331888 polymorphism within CLU was significantly associated with an increased risk of LOAD (OR=1.39, 95% CI=1.13-1.72, P=0.002). Logistic regression analysis revealed that the rs9331888 polymorphism presented strong associations with LOAD in the dominant, recessive and additive models. No significant differences in genotype and allele frequencies of the rs2279590 and rs11136000 polymorphisms were found between LOAD patients and controls. Haplotype analysis identified a risk haplotype (CCG) (OR=1.66) and a protective haplotype (CCC)(OR=0.70). CONCLUSIONS: Our findings implicate CLU as a susceptibility gene for LOAD in Han Chinese.