Lack of association between triggering receptor expressed on myeloid cells 2 polymorphism rs75932628 and late-onset Alzheimer's disease in a Chinese Han population.
Ontology highlight
ABSTRACT:
SUBMITTER: Wang P
PROVIDER: S-EPMC5757673 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) acts as a potential genetic modifier for Alzheimer's disease (AD). Previous reports identified that HMGCR rs3846662 polymorphism is associated with biosynthesis of cholesterol in AD pathology. In order to assess the involvement of the HMGCR polymorphism in the risk of late-onset AD (LOAD) in northern Han Chinese, we performed a case-control study of 2334 unrelated subjects (984 cases and 1350 age- and gender-matched controls) to evaluate the genotype and allele distributions of the HMGCR rs3846662 with LOAD. The genotype distribution (GG, AG, AA) of rs3846662 was significantly different between LOAD patients and controls (P = 0.003), but the allele distribution did not reach a significant difference (P = 0.614). After adjusting for age, gender and the APOE ?4 status, the minor A allele of rs3846662 was validated as a protective factor for LOAD in dominant model (OR = 0.796, P = 0.02, 95% CI = 0.657-0.965). Interestingly, we observed rs3846662 polymorphism was only significantly associated with LOAD in APOE ?4 non-carriers (OR = 0.735, P = 0.005, 95% CI = [0.593, 0.912]). In conclusion, our study demonstrates A allele of HMGCR rs3846662 acts as a protective factor for LOAD in northern Han Chinese.
| S-EPMC5008397 | biostudies-literature
Project description:In a recent genome-wide association study, the SLC26A4 gene rs2072064 polymorphism was found to be associated with late-onset Alzheimer's disease in Caucasians. Here, we investigated this association in a large Northern Han Chinese cohort consisting of 599 sporadic late-onset Alzheimer's disease patients and 598 healthy controls matched for sex and age in a Northern Han Chinese population from Qingdao, China. Genotyping by the polymerase chain reaction-ligase detection reaction revealed that there were significant differences in the genotype (P = 0.017) and allele (P = 0.007) frequencies of the rs2072064 polymorphism between late-onset Alzheimer's disease patients and controls. The A allele of this polymorphism was significantly associated with a reduced risk of late-onset Alzheimer's disease (odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.670-0.937, P = 0.007). When the data were stratified by the apolipoprotein E ?4 status, there was a significant difference only among apolipoprotein E ?4 non-carriers (genotypic P = 0.001, allelic P = 0.001). Furthermore, the association between rs2072064 and late-onset Alzheimer's disease remained significant by logistic regression analysis after adjustment for age, gender, and the apolipoprotein E ?4 carrier status (dominant model: OR = 0.787, 95% CI = 0.619-1.000, P = 0.050; recessive model: OR = 0.655, 95% CI = 0.448-0.959, P = 0.030; additive model: OR = 0.792, 95% CI = 0.661-0.950, P = 0.012). These findings suggest that SLC26A4 is a susceptibility gene for late-onset Alzheimer's disease in a Northern Han Chinese population from the Qingdao area.
| S-EPMC4146073 | biostudies-literature
Project description:The myocyte enhancer factor (MEF2) family of transcription factors plays a vital role in memory and learning due to its functions in regulating synapse number and reducing dendritic spines. Myocyte enhancer factor 2 C (MEF2C) is regarded as modulator of amyloid-protein precursor (APP) proteolytic processing, in which amyloid-β (Aβ) is produced. A common single nucleotide polymorphism (SNP, rs190982) in MEF2C gene was identified to be related to late-onset Alzheimer's disease (LOAD) in Caucasians in a large meta-analysis of genome-wide association studies (GWAS). Here, we recruited unrelated 984 LOAD patients and 1348 healthy controls matched for gender and age to ascertain whether the rs190982 polymorphism is related to LOAD in Han Chinese. No difference in the genotype and allele distributions of the MEF2C rs190982 polymorphism was found between LOAD cases and healthy controls (genotype: P = 0.861; allele: P = 0.862), even after stratification for APOE ε4 allele as well as statistical adjustment for age, gender and APOE ε4 status. Furthermore, the meta-analysis in 4089 Chinese individuals did not detect the association of rs190982 within MEF2C with the risk for LOAD (OR = 1.03, 95%CI = 0.90-1.18). Overall, the current evidence did not support the relation between rs190982 polymorphism within MEF2C and the LOAD risk in Northern Han Chinese.
| S-EPMC5129919 | biostudies-literature
Project description:The variations of SORCS1 gene may play potential key roles in late-onset Alzheimer's disease (LOAD). To evaluate the relationship between the polymorphism of SORCS1 gene and LOAD in the ethnic Han Chinese, we conducted a case-control study to investigate the association between the single-nucleotide polymorphisms (SNPs) in intron 1 of SORCS1 and LOAD in Chinese Han population. Six reported SNPs in intron 1 of SORCS1 were analyzed by Snapshot, genotyping and haplotyping in 236 Chinese LOAD cases and 233 matched controls. The significant differences in frequencies of two SNPs (rs10884402, rs950809) were found between the two groups. In addition, haplotype analyses revealed that, in the LOAD group, the frequency of haplotypes C-C-G-T-C (alleles in order of rs17277986, rs6584777, rs10884402, rs7078098, rs950809 polymorphisms) were significantly higher (Psim<0.0001) while haplotype C-C-A-T-C, C-C-A-C-C, T-T-A-C-C were significantly lower (Psim<0.0001). Our data suggested that the genetic variation of the rs10884402 and rs950809 in intron 1 of SORCS1 was associated with the late-onset AD in the Chinese Han population.
| S-EPMC3659081 | biostudies-literature
Project description:AimsTo investigate the impact of sortilin-related receptor 1 gene 1 (SORL1) and peroxisome proliferator activated receptor gamma (PPAR G) gene single nucleotide polymorphisms (SNPs), gene- gene and gene- environment interactions and haplotype on late-onset Alzheimer's disease (LOAD) risk.MethodsHardy-Weinberg equilibrium (HWE), haplotype analysis and pairwise linkage disequilibrium (LD) analysis were investigated by using SNPStats (available online at http://bioinfo.iconcologia.net/SNPstats). Logistic regression was performed to investigate association between SNPs and LOAD. Generalized multifactor dimensionality reduction (GMDR) was used to investigate the interaction among gene- gene and gene- environment interaction.ResultsLogistic regression analysis showed that LOAD risk was significantly higher in carriers of the A allele of rs1784933 polymorphism than those with GG (GA+ AA versus GG), adjusted OR (95%CI) = 1.63(1.27-1.98), and higher in carriers of G allele of the rs1805192 polymorphism than those with CC (CG+ GG versus CC), adjusted OR (95%CI) = 1.70 (1.25-2.27). GMDR analysis suggested a significant two-locus model (p = 0.0010) involving rs1784933 and rs1805192, and a significant two-locus model (p = 0.0100) involving rs1784933 and alcohol drinking. Haplotype containing the rs1784933- A and rs689021- C alleles were associated with a statistically increased LOAD risk (OR = 1.86, 95%CI = 1.37- 2.52, p < 0.001).ConclusionsWe conclude that rs1784933 and rs1805192 minor alleles, gene- gene interaction between rs1784933 and rs1805192, gene- environment interaction between rs1784933 and alcohol drinking, and haplotype containing the rs1784933- A and rs689021- C alleles are all associated with increased LOAD risk.
| S-EPMC5564649 | biostudies-literature
Project description:BACKGROUND:Triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify inflammation and serves as a critical mediator of inflammatory response in the context of sepsis. To date, the predisposition of TREM-1 gene polymorphisms to septic shock has not been reported. This study was designed to investigate whether TREM-1 genomic variations are associated with the development of septic shock. METHODS:We genotyped two TREM-1 single nucleotide polymorphisms (SNPs, rs2234237 and rs2234246) and evaluated the relationships between these SNPs and septic shock on susceptibility and prognosis. RESULTS:TREM-1 rs2234246 A allele in the promoter region was significantly associated with the susceptibility of septic shock in recessive model (AA, OR=3.10, 95%CI 1.15 to 8.32, P=0.02), and in codominant model (AG, OR=0.72, 95%CI 0.43-1.19, P=0.02; AA, OR=2.71, 95%CI 1.00-7.42; P=0.03). However, in three inherited models (dominant model, recessive model, and codominant model), none of the assayed loci was significantly associated with the prognosis of septic shock. The non-survivor group demonstrated higher plasma IL-6 levels (99.7±34.7 pg/mL vs. 61.2±26.5 pg/mL, P<0.01) than the survivor group. Plasma concentrations of IL-6 among the three genotypes of rs2234246 were AA 99.4±48.9 pg/mL, AG 85.4±43 pg/mL, and GG 65.3±30.7 pg/mL (P<0.01). The plasma concentrations of IL-6 in patients with AA genotypes were significantly higher than those in patients with GG genotypes (P<0.01). CONCLUSION:TREM-1 genetic polymorphisms rs2234246 may be significantly correlated only with susceptibility to septic shock in the Chinese Han population.
| S-EPMC4458472 | biostudies-literature
Project description:Recently, a large genome-wide association study (GWAS) has identified a novel variant (rs1476679) within ZCWPW1 showing strong association with late-onset Alzheimer's disease (LOAD) in Caucasian. However, the effect of rs1476679 on other populations remains unclear. In order to explore whether rs1476679 is also associated with the LOAD risk in other ethnic groups, we recruited 2350 unrelated Northern Han Chinese subjects, which include 992 LOAD patients and 1358 healthy controls. Analysis of data from these subjects suggests that the rs1476679 polymorphism is significantly associated with the LOAD (genotype P = 0.017, allele P = 0.044). The logistic regression reveals the C allele at rs1476679 is a protective factor for LOAD in the dominant model (OR = 0.779, 95%CI = 0.659-0.921, Pc = 0.009) adjusting for gender, age and APOE ε4 status. Furthermore, rs1476679 can decrease the AD risk (Dominant: OR = 0.733, 95%CI = 0.607-0.884, Pc = 0.006; Additive: OR = 0.820, 95%CI = 0.708-0.950, Pc = 0.048) in APOE ε4 non-carriers after stratification. Furthermore, meta-analysis of 82525 individuals confirmed that rs1476679 within ZCWPW1 decreased the risk of LOAD (OR = 0.91, 95%CI = 0.89-0.94). To summarize, the rs1476679 polymorphism in ZCWPW1 is associated with LOAD in Northern Han Chinese population.
| S-EPMC4991456 | biostudies-literature
Project description:Several polymorphisms in hepatic lipase (LIPC) are similar to apoE4 because they associate with cholesterol concentrations and, for rs6084, coronary artery disease (CAD). Since apoE4 is also a primary genetic risk factor for late-onset Alzheimer's disease (LOAD), LIPC single nucleotide polymorphisms (SNP)s represent excellent candidates for LOAD association studies. Because this issue has not been addressed previously, we evaluated LIPC SNP association with LOAD. In a population from the Religious Orders Study (ROS), rs6084 was nominally associated with LOAD odds (p=0.015 by chi(2) test). However, this association was not confirmed in two subsequent series based at the University of Kentucky (UKY, p=0.15) or the Mayo Clinic in Jacksonville (MCJ, p=0.97). Hence, rs6084 is not consistently associated with LOAD.
| S-EPMC2362140 | biostudies-literature
Project description:The present study aimed to estimate the association between susceptibility to migraine and the 12-nucleotide insertion/deletion (indel) polymorphism in promoter region of alpha(2B)-adrenergic receptor gene (ADRA2B).A case-control study was carried out in Chinese Han population, including 368 cases of migraine and 517 controls. Genomic DNA was extracted from blood samples, and DNA fragments containing the site of polymorphism were amplified by PCR. Data were adjusted for sex, age, migraine history and family history, and analyzed using a logistic regression model.There was no association between indel polymorphism and migraine, at either the allele or the genotype level.These findings do not support a functional significance of ADRA2B indel polymorphism at position -4825 relative to the start codon in the far upstream region of the promoter in the present migraine subjects.
| S-EPMC5552571 | biostudies-other
Project description:The R47H variant in the microglial triggering receptor expressed on myeloid cell 2 (TREM2) receptor is a strong risk factor for Alzheimer's disease (AD). To characterize processes affected by R47H, we performed an integrative network analysis of genes expressed in brains of AD patients with R47H, sporadic AD without the variant, and patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), systemic disease with early-onset dementia caused by loss-of-function mutations in TREM2 or its adaptor TYRO protein tyrosine kinase-binding protein (TYROBP). Although sporadic AD had few perturbed microglial and immune genes, TREM2 R47H AD demonstrated upregulation of interferon type I response and pro-inflammatory cytokines accompanied by induction of NKG2D stress ligands. In contrast, PLOSL had distinct sets of highly perturbed immune and microglial genes that included inflammatory mediators, immune signaling, cell adhesion, and phagocytosis. TREM2 knockout (KO) in THP1, a human myeloid cell line that constitutively expresses the TREM2- TYROBP receptor, inhibited response to the viral RNA mimetic poly(I:C) and phagocytosis of amyloid-beta oligomers; overexpression of ectopic TREM2 restored these functions. Compared with wild-type protein, R47H TREM2 had a higher stimulatory effect on the interferon type I response signature. Our findings point to a role of the TREM2 receptor in the control of the interferon type I response in myeloid cells and provide insight regarding the contribution of R47H TREM2 to AD pathology.
| S-EPMC7546799 | biostudies-literature