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Abstract: Tau-tubuline kinase 1 (TTBK1) is a recently discovered brain-specific protein kinase involved in tau phosphorylation at AD-related sites. A recent large study has identified significant association of two single nucleotide polymorphisms (SNPs) (rs2651206 and rs7764257) in the TTBK1 gene with late-onset Alzheimer''s disease (LOAD) in Spanish. Here, we performed a case–control study to clarify whether the risk for LOAD might be influenced by these polymorphisms in a large Chinese cohort consisting of 400 patients and 388 healthy controls. The minor alleles of the rs2651206 polymorphism within TTBK1 was significantly associated with a reduced risk of LOAD (odds ratio/OR=0.69, P =0.011). Furthermore, rs2651206 polymorphism was still strongly associated with LOAD (OR=0.72, P =0.05) after adjusted for age, gender, and the apolipoprotein E (APOE) ɛ4 status. Haplotype analysis identified the TG haplotype, deriving from the two minor alleles, to decrease the risk of LOAD (OR=0.78, P =0.037). This study provides the evidence that variations in the TTBK1 gene may play an important role in the pathogenesis of sporadic LOAD in a Han Chinese population. [Copyright &y& Elsevier]

Abstract: Background: Stroke is the second most common cause of death in developed countries and a major cause of adult disability and mortality worldwide. New data strongly suggest that neuropeptide Y (NPY) may be a candidate gene for ischemic stroke. Methods: We investigated 450 ischemic stroke patients and 423 healthy controls matched for sex and age in a Han Chinese population. Three functional polymorphisms (−883TGins/del, −602G/T and −399 T/C) located in NPY gene promoter were genotyped using DNA sequencing methods. Results: Of 3 NPY polymorphisms investigated in our study, the −399CC genotype (OR: 1.699, 95% CI: 1.124–2.567, P =0.011) and the −399C allele (OR: 1.254, 95% CI: 1.031–1.524, P =0.023) were more frequent among ischemic stroke patients than in controls, especially in the small vessel disease (SVD) subtype patients. The similar results were observed in multivariable logistic regression analysis. Haplotype analysis revealed that the −883ins/−399C haplotype was a risk marker for ischemic stroke (P =0.008). Conclusions: The C allele of −399 T/C polymorphism in the promoter regions of NPY is an independent risk factor for ischemic stroke, suggesting that NYP system may involve in the mechanisms of stroke pathology. [Copyright &y& Elsevier]

Abstract: Ischemic stroke (IS) is a major cause of morbidity and mortality around the world. Interleukin-18 (IL-18) plays an important role in the pathogenesis of IS and IL-18 promoter polymorphisms have been shown to be associated with levels of expression of IL-18. We investigated the association of two functional polymorphisms in IL-18 promoter, −607C/A (rs1946518) and −137G/C (rs187238), with the risk of ischemic stroke in a Han Chinese population of 423 patients and 384 healthy controls matched for sex and age. The results revealed that the −607C allele was associated with an increased risk of IS with an odds ratios (OR) of 1.358 (P =0.002, power=100%) and the presence of the −137G allele was correlated with increased the risk of IS in the subtype of patients with large artery atherosclerosis (LAA) (OR=1.583, P =0.02, power=94%). Patients with the −607C/−137G haplotype also had significantly increased risk of IS compared to controls (OR=1.341, P =0.005, power=100%). Our findings suggest that these functional polymorphisms in the IL-18 promoter are involved in development of IS in the Han Chinese population. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: PICALM might play an important role in AD pathology through participating in altering synaptic vesicle cycling or APP endocytosis. A recent genome-wide study (GWAS) identified a single nucleotide polymorphism (SNP) rs3851179 in the 5′ to the PICALM gene strongly associated with Alzheimer''s disease (AD) in Caucasians. In order to assess the involvement of the PICALM polymorphism in the risk of developing late-onset AD (LOAD), we analyzed the genotype and allele distributions of these three polymorphisms in 609 Han Chinese subjects. Our data showed no significant association between the PICALM rs3851179 polymorphism and LOAD (genotype distribution: P =0.43; allele frequency: P =0.25, odds ratio=0.87, 95% confidence interval=0.68 to 1.10), even after statistical adjustment for age, gender and apolipoprotein E (APOE) status. Our results suggest that the PICALM polymorphism may not play a major role in the development of LOAD in the Han Chinese population. [Copyright &y& Elsevier]