Alzheimer's Disease In Chinese Population Research Articles

DHCR7 rs12785878 T>C Polymorphism Is Associated With an Increased Risk of Early Onset of Alzheimer's Disease in Chinese Population

Background: Vitamin D insufficiency has been considered a risk factor for Alzheimer's disease (AD) in several studies. Recently, four single-nucleotide polymorphisms (SNPs) to be genome-wide significant for 25-hydroxyvitamin D [25(OH)D] were identified to have an association with the risk of AD. These include GC rs2282679 A>C, CYP2R1 rs10741657 T>C, DHCR7 rs12785878 T>C, and CYP24A1 rs6013897 T>A. However, the association between these polymorphisms and AD susceptibility in the Chinese population remains unclear.Methods: A case-control cohort study was conducted in 676 AD patients (mean age at onset was 69.52 ± 10.90 years, male: 39.2%) and 551 healthy controls (mean age was 67.73 ± 6.02 years, male: 44.8%). Genotyping was determined by PCR and SNaPshot sequencing. To determine whether the four SNPs account for risks in AD in Chinese population, multivariate logistic regression models were performed. Stratified analysis was performed based on gender and age of onset of AD, separately. Statistical significance was set at 0.0125 (0.05/4) based on Bonferroni correction.Findings: DHCR7 rs12785878 T>C was found to be significantly associated with an increased risk of early-onset Alzheimer's disease (EOAD) (n = 300, risk allele C, adjusted OR = 1.542, adjusted 95% CI = 1.176–2.023, p = 0.002). There was no statistical significance of the other three SNPs between the two groups.Interpretation: Our results suggested that DHCR7 rs12785878 T>C might be associated with an increased risk of EOAD in the Chinese population, while other polymorphisms related to vitamin D insufficiency might not be. However, due to the limited data in this study, replication studies in a larger sample are required.

Association of Apolipoprotein E (ApoE) Polymorphism with Alzheimer's Disease in Chinese Population.

Apolipoprotein E (ApoE) plays a vital role in cholesterol metabolism and its allele polymorphisms have been associated with several diseases including Alzheimer's disease (AD). There are few systematic studies on ApoE polymorphism and its association with AD in Chinese population. To examine this issue, participants included 4251 subjects and 404 AD patients with 390 healthy elderly residing in Chongqing city were genotyped. The results showed that the ε3 allele presented the highest frequency (82%), followed by ε4 (6.25%) and ε2 (11.75%) in general population. ε3/ε3 genotype carriers are the most common ones (64.19%) and the ε4/ε4 had the lowest frequency (0.59%). The frequency of ApoEε4 allele frequency in AD (15.35%) was significantly higher than control (10.00%). Those carriers of two ε4 allele have five time higher risk to develop AD. Our study demonstrate that ApoEε4 allele is a risk factor of AD for Chinese population.

PICALM rs3851179 Variant Confers Susceptibility to Alzheimer's Disease in Chinese Population.

The association between PICALM rs3851179 variant and Alzheimer's disease (AD) has been well established by previous genome-wide association studies (GWAS) and candidate gene studies in European population. Recent studies investigated the association between PICALM rs3851179 and AD susceptibility in Chinese population. However, these studies reported consistent and inconsistent results. Here, we selected 9435 samples including 3704 AD cases and 5731 controls from previous studies and evaluated this association using a meta-analysis method for additive model. We did not observe significant genetic heterogeneity in Chinese population. Our results indicate significant association between PICALM rs3851179 and AD in Chinese population. The sensitivity analysis indicates that the association between rs3851179 and AD did not vary substantially. The regression analysis suggests no significant publication bias. In summary, this updated meta-analysis highlights the involvement of PICALM rs3851179 variant in Alzheimer's disease susceptibility in Chinese population.

CR1 rs3818361 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Chinese Population.

Recent genome-wide association studies (GWAS) reported CR1 rs3818361 polymorphism to be an Alzheimer's disease (AD) susceptibility variant in European ancestry. Three independent studies investigated this association in Chinese population. However, these studies reported weak or no significant association. Here, we reinvestigated the association using all the samples from three independent studies in Chinese population (N = 4047, 1244AD cases and 2803 controls). We also selected three independent studies in European ancestry population (N = 11787, 3939AD cases and 7848 controls) to evaluate the effect of rs3818361 polymorphism on AD risk in different ethnic backgrounds. In Chinese population, we did not identified significant heterogeneity using additive, recessive, and dominant genetic models. Meta-analysis showed significant association between rs3818361 and AD with P = 6.00E-03 and P = 5.00E-03. We further identified no heterogeneity of rs3818361 polymorphism between Chinese and European populations. We found that rs3818361 polymorphism contributed to AD with similar genetic risk in Chinese and European populations. In summary, this is the first study to show significant association between rs3818361 polymorphism and AD in Chinese population by a meta-analysis method. Our findings indicate that the effect of CR1 rs3818361 polymorphism on AD risk in Chinese cohorts is consistent with the increased risk observed in European AD cohorts.

Angiotensin-converting enzyme gene insertion-deletion polymorphism is a risk marker for Alzheimer's disease in a Chinese population: a meta-analysis of case-control studies.

It has long been known that the polymorphisms of angiotensin-converting enzyme gene (ACE) are associated to increase risk of Alzheimer's disease (AD) in Chinese population. However, consistent results were not obtained among studies. This study is aimed to clarify the association between ACE insertion (I)/deletion (D) polymorphism (rs1799752) and AD. Literatures were searched from PubMed, Embase, Cochrane Library, CNKI, Wanfang and VIP databases without language restrictions. Eleven separate studies were suitable for the inclusion criterion. The selected studies contained 2,763 Chinese participants, including 1,383 in AD group and 1,380 controls. Pooled odds ratios (ORs) were calculated to assess the association between ACE I/D polymorphism and AD. Our case-control data indicated that ACE insertion is a risk allele in all genetic models: additive model (I vs. D: OR = 1.32, 95 % CI 1.07-1.62, P = 0.008), dominant model (II + ID vs. DD: OR = 1.61, 95 % CI 1.08-2.41, P = 0.02) and recessive model (II vs. ID + DD: OR = 1.39, 95 % CI 1.07-1.81, P = 0.01). Heterogeneity between studies was significant (P < 0.10) but not in stratification defined by the selection of controls (P > 0.10). After stratification according to the selection of controls, the carrier of ACE I allele remained a high risk for AD in population-based samples subgroup (I vs. D: P = 0.008, OR = 1.32, 95 % CI 1.07-1.61, P(heterogeneity) = 0.47, I (2) = 0 %). Our study provided solid evidence suggesting that ACE gene I/D polymorphism is a genetic risk factor for AD in Chinese population.

Estrogen receptor 1 PvuII and XbaI polymorphisms and susceptibility to Alzheimer's disease: a meta-analysis.

The aim of this study was to explore whether estrogen receptor 1 (ESR1) PvuII and XbaI polymorphisms are associated with susceptibility to Alzheimer's disease (AD). We conducted a meta-analysis of the associations between AD and ESR1 PvuII and XbaI polymorphisms as well as haplotypes of the ESR1 PvuII and XbaI polymorphisms. A total of 1359 patients and 1387 controls from 9 studies on the ESR1 PvuII polymorphism and 1525 patients and 1575 controls from 8 studies on the ESR1 XbaI polymorphism were included in this meta-analysis. Gender-specific meta-analysis showed an association between the ESR1 PP+Pp genotype and AD in males (OR = 0.302, 95%CI = 0.100-0.914, P = 0.034), but not in females. No association was observed between AD and the ESR1 XbaI X allele (OR = 1.114, 95%CI = 0.868-1.429, P = 0.397). However, country-specific meta-analysis identified an association between AD and the ESR1 X allele in Japanese (OR = 1.386, 95%CI = 1.055-1.822, P = 0.019), but not Chinese or Italian populations. Meta-analyses results indicated an association between the PP/XX haplotypes and AD in Chinese population (OR for PP/XX vs others = 2.758, 95%CI = 1.750-4.346, P = 1.2 x 10(-6)). This meta-analysis showed associations between the ESR1 PvuII polymorphism and AD susceptibility in males, between AD risk and the ESR1 XbaI polymorphism in the Japanese population, and between the PP/XX haplotype and AD susceptibility in the Chinese population.

CD33 rs3865444 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Chinese, European, and North American Populations.

The CD33 rs3865444 polymorphism was first identified to be associated with Alzheimer's disease (AD) in European population. However, the following studies reported weak or no significant association in Chinese, Japanese, Korean, American, and Canadian populations. We think that these negative results may have been caused by either relatively small sample sizes compared with those used for the previous GWAS in European ancestry or the genetic heterogeneity of the rs3865444 polymorphism in different populations. Here, we reevaluated this association using the relatively large-scale samples from previous 27 studies (N = 86,759; 31,106 cases and 55,653 controls) by searching the PubMed, AlzGene, and Google Scholar databases. We identified significant heterogeneity and observed no significant association between the rs3865444 polymorphism and AD in pooled populations (P = 0.264, odds ratio (OR) = 0.97, 95% confidence interval (CI) 0.93-1.02). In subgroup analysis, we identified significant heterogeneity only in East Asian population and observed no significant association between the rs3865444 polymorphism and AD. We further identified significant heterogeneity and observed significant association between the rs3865444 polymorphism and AD in Chinese population. We identified no significant heterogeneity and significant association in North American and European populations. Collectively, our analysis shows that the CD33 rs3865444 polymorphism is associated with AD susceptibility in Chinese, European, and North American populations. We believe that our findings will be very useful for future genetic studies on AD.

The polymorphism of ARNTL2 (BMAL2) gene rs2306074 C>T is associated with susceptibility of Alzheimer disease in Chinese population

In the present study, we investigated whether polymorphism of ARNTL2 (BMAL2) gene rs2306074 T/C was associated with susceptibility of Alzheimer disease (AD) in Chinese population. A case-control method was employed in this study. 296 unrelated AD patients and 423 control subjects were recruited in current study. The prevalence of C carriers in BMAL2 gene rs2306074 T/C in AD patients was significantly higher than that of control subjects in both the whole sample and APOE ε 4 non-carriers (in the whole sample: χ (2) = 5.938, P = 0.012; in APOE ε 4 non-carriers: χ (2) = 9.048, P < 0.0001). In addition, both in the whole sample and APOE ε 4 non-carriers, prevalence of CC genotypes in BMAL2 gene rs2306074 of AD patients was also significantly higher than that in controls (in the whole sample: χ (2) = 5.126, P = 0.018; in APOE ε 4 non-carriers: χ (2) = 7.389, P = 0.023). However, there was no significant difference of prevalence of C carriers and CC genotypes in BMAL2 gene rs2306074 T/C between AD patients and control subjects among APOE ε 4 carriers (C carriers: χ (2) = 0.020, P = 0.900; CC genotypes: χ (2) = 0.017, P = 0.946). C carriers in BMAL2 gene rs2306074 T/C are associated with a high susceptibility of AD among APOE ε 4 non-carriers but not among APOE ε 4 carriers in Chinese population.

Apolipoprotein E gene polymorphism and Alzheimer's disease in Chinese population: a meta-analysis

The relationship between Apolipoprotein E (ApoE) genotype and the risk of Alzheimer's disease (AD) is relatively well established in Caucasians, but less established in other ethnicities. To examine the association between ApoE polymorphism and the onset of AD in Chinese population, we searched the commonly used electronic databases between January 2000 and November 2013 for relevant studies. Total 20 studies, including 1576 cases and 1741 controls, were retrieved. The results showed statistically significant positive association between risk factor ε4 allele carriers and AD in Chinese population (OR = 3.93, 95% CI = 3.37–4.58, P < 0.00001). Genotype ApoE ε4/ε4 and ε4/ε3 have statistically significant association with AD as well (ε4/ε4: OR = 11.76, 95% CI = 6.38–21.47, P < 0.00001; ε4/ε3: OR = 3.08, 95% CI = 2.57–3.69, P < 0.00001). Furthermore, the frequency of the ApoE ε3 is lower in AD than that in the health controls, and the difference of ε3 allele is also statistically significant (OR = 0.42, 95% CI = 0.37–0.47, P < 0.00001). No significant heterogeneity was observed among all studies. This meta-analysis suggests that the subject with at least one ApoE ε4 allele has higher risk suffering from AD than controls in Chinese population. The results also provide a support for the protection effect of ApoE ε3 allele in developing AD.

The Polymorphism of CLOCK Gene 3111T/C C>T Is Associated With Susceptibility of Alzheimer Disease in Chinese Population

ObjectivesIn the present study, it was examined whether polymorphism of circadian locomotor output cycle kaput (CLOCK) gene 3111T/C was associated with susceptibility of Alzheimer disease (AD).MethodsThis study was conducted using...

Association between the Polymorphism of Estrogen Receptor á and Alzheimer's Disease in Chinese Population

To investigate the possible association between the polymorphism of estrogen receptor alpha (ERalpha) and Alzheimer's disease (AD) in Chinese population. Cognitive function of patients with AD was evaluated with the Modified Mini-Mental Status Examination (MMSE). ERalpha polymorphism was detected in 236 AD patients and 236 control individuals. Logistic regression was used in age, body mass index, education, depression, hypertension, diabetes, history of stroke, smoking status, ApoE e4 carrier, and estrogen receptor a genotypes to calculate their odds ratios. There were no significant differences in PvuII allele and genotype between AD patients and control individuals. The frequencies of XbaI x allele and XbaI xx genotype were significantly higher in AD patients than in control individuals (chi2 = 28.116, df = 1, p < 0.0001 and chi2 = 16.628, df = 2, p < 0.0001, respectively). The odds ratio for the patients with xx genotype was 2.12 (95% CI = 1.63 - 2.76, p < 0.01). These findings suggest that ERalpha XbaI polymorphism is associated with an increased risk of AD in Chinese population. More research is needed to determine the mechanism by which ERalpha polymorphisms is associated with AD.

The prevalence of CD33 and MS4A6A variant in Chinese Han population with Alzheimer’s disease

CD33 and MS4A6A genes play potential key roles in the pathogenesis of Alzheimer's disease (AD). One recent genome-wide association study has revealed that the rs3865444 polymorphism in the CD33 gene and rs610932 polymorphism in the MS4A6A gene are associated with susceptibility to AD in Caucasians. To evaluate the relationship between the polymorphism of the CD33, MS4A6A gene and AD in the ethnic Chinese Han, we conducted a case-control study (n = 383, age > 54) to determine the prevalence of single-nucleotide polymorphism of two genes in patients with AD in Chinese population of Mainland, and clarified whether these polymorphisms are risk factors for AD. The prevalence of the allele (T) in the rs3865444 polymorphism of the CD33 gene and allele (C) in rs610932 polymorphism of the MS4A6A gene was significantly different in AD patients and control subjects (P < 0.001, respectively), and the results were not influenced by age, gender, or APOE status. Our data revealed the allele (T) of the rs3865444 polymorphism of the CD33 gene and the allele (C) of the rs610932 polymorphism of the MS4A6A gene may contribute to AD risk in the Chinese Han population.

The MTHFD1L gene rs11754661 marker is associated with susceptibility to Alzheimer's disease in the Chinese Han population

Our objective is to evaluate the relationship between the rs11754661 polymorphism of the MTHFD1L gene and Alzheimer's disease (AD) in the ethnic Chinese Han. We conducted a case-control study (n=380, age>50) to determine the prevalence of one common single-nucleotide polymorphism (SNP) of MTHFD1L (rs11754661) in patients with AD in Chinese population of Mainland China, and clarified whether this polymorphism is a risk factor for AD. The prevalence of the minor allele (A) in the rs11754661 polymorphism was significantly different in AD patients and control subjects (P<0.01). The rs11754661 polymorphism was associated with AD in the ethnic Chinese Han (OR=1.829, 95% CI: 1.277-2.619, P=0.001), and the results were influenced by APOE status. Our data revealed that the allele (A) of the rs11754661 polymorphism within MTHFD1L gene may contribute to AD risk in the Chinese Han population.

A single nucleotide polymorphism in LRP2 is associated with susceptibility to Alzheimer's disease in the Chinese population

Background LRP2 (also called megalin) plays a potential key role in the pathogenesis of Alzheimer's disease (AD). Recently, one genome-wide association study has revealed that the rs3755166 (G/A) polymorphism located in the LRP2 promoter is associated with development of AD in Caucasians, while there are no studies on the association LRP2 of with AD risk in Asians. Methods To evaluate the relationship between the rs3755166 polymorphism of the LRP2 gene and AD in the ethnic Chinese Han, we conducted a case-control study (n = 361, age > 50) to determine the prevalence of one common single-nucleotide polymorphism (SNP) of LRP2 (rs3755166) in patients with AD in Chinese population of Mainland China, and clarified whether this polymorphism is a risk factor for AD. Results The prevalence of the minor allele (A) in the rs3755166 polymorphism was significantly different in AD patients and control subjects (P < 0.05). The rs3755166 polymorphism was associated with AD in the ethnic Chinese Han (OR = 1.378, 95% CI: 1.017-1.867, P = 0.039), and the results were not influenced by age, gender, or APOE status (P = 0.441, P = 0.94, P = 0.432, respectively). Conclusion Our data revealed the allele (A) of the rs3755166 polymorphism within LRP2 gene may contribute to AD risk in the Chinese Han Population.