Dataset Information

Genetic Association of FERMT2, HLA-DRB1, CD2AP, and PTK2B Polymorphisms With Alzheimer's Disease Risk in the Southern Chinese Population.

ABSTRACT: Objectives:This study aimed to explore the relationship between 18 single nucleotide polymorphisms (SNPs) and Alzheimer's disease (AD) within the southern Chinese population. Methods:A total of 420 participants, consisting of 215 AD patients and 205 sex- and age-matched controls, were recruited. The SNaPshot technique and polymer chain reaction (PCR) were used to detect the 18 SNPs. Combined with the apolipoprotein E (APOE) ?4 allele and age at onset, we performed an association analysis between these SNPs and AD susceptibility. Furthermore, we analyzed SNP-associated gene expression using the expression quantitative trait loci analysis. Results:Our study found that rs17125924 of FERMT2 was associated with the risk of developing AD in the dominant (P = 0.022, odds ratio [OR] = 1.57, 95% confidence interval [CI]: 1.07-2.32) and overdominant (P = 0.005, OR = 1.76, 95% CI: 1.18-2.61) models. Moreover, compared with APOE ?4 non-carriers, the frequency of the G-allele at rs17125924 was significantly higher among AD patients in APOE ?4 allele carriers (P = 0.029). The rs9271058 of HLA-DRB1 (dominant, overdominant, and additive models), rs9473117 of CD2AP (dominant and additive models), and rs73223431 of PTK2B (dominant, overdominant, and additive models) were associated with early onset AD (EOAD). Using the genotype-tissue expression (GTEx) and Braineac database, we found a significant association between rs9271058 genotypes and HLA-DRB1 expression levels, while the CC genotype at rs9473117 and the TT genotype of rs73223431 increased CD2AP and PTK2B gene expression, respectively. Conclusion:Our study identifies the G-allele at rs17125924 as a risk factor for developing AD, especially in APOE ?4 carriers. In addition, we found that rs9271058 of HLA-DRB1, rs9473117 of CD2AP, and rs73223431 of PTK2B were associated with EOAD. Further studies with larger sample sizes are needed to confirm our results.

SUBMITTER: Yan Y

PROVIDER: S-EPMC7010721 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Genetic Association of FERMT2, HLA-DRB1, CD2AP, and PTK2B Polymorphisms With Alzheimer's Disease Risk in the Southern Chinese Population.

Yan Yi Y Zhao Aonan A Qui Yinghui Y Li Yuanyuan Y Yan Ran R Wang Ying Y Xu Wei W Deng Yulei Y

Frontiers in aging neuroscience 20200204

<h4>Objectives</h4>This study aimed to explore the relationship between 18 single nucleotide polymorphisms (SNPs) and Alzheimer's disease (AD) within the southern Chinese population.<h4>Methods</h4>A total of 420 participants, consisting of 215 AD patients and 205 sex- and age-matched controls, were recruited. The SNaPshot technique and polymer chain reaction (PCR) were used to detect the 18 SNPs. Combined with the <i>apolipoprotein E</i> (<i>APOE</i>) ε4 allele and age at onset, we performed an ...[more]

PMID: 32116649

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Project description:BackgroundAlzheimer's disease (AD) is a multi-gene inherited disease, and apolipoprotein E (APOE) ɛ4 is a strong risk factor. Other genetic factors are important but limited.ObjectiveThis study aimed to investigate the relationship between 17 single-nucleotide polymorphisms (SNPs) and AD in the Southern Chinese populations.MethodsWe recruited 242 AD patients and 208 controls. The SNaPshot technique was used to detect the SNPs.ResultsAdjusted for sex and age, we found rs6572869 (FERMT2), rs11604680 (CELF1), and rs1317149 (CELF1) were associated with AD risk in the dominant (rs6572869: p = 0.022, OR = 1.55; rs11604680: p = 0.007, OR = 1.68; rs1317149: p = 0.033, OR = 1.50) and overdominant models (rs6572869: p = 0.001, OR = 1.96; rs11604680: p = 0.002, OR = 1.82; rs1317149: p = 0.003, OR = 1.80). rs9898218 (COPI) was associated with AD risk in the overdominant model (p = 0.004, OR = 1.81). Further, rs2741342 (CHRNA2) was associated with AD protection in the dominant (p = 0.002, OR = 0.5) and additive models (p = 0.002, OR = 0.64). Mutations in rs10742814 (CELF1), rs11039280 (CELF1), and rs3752242 (ABCA7) contributed to AD protection. Among them, rs10742814 (CELF1), rs3752242 (ABCA7), and rs11039280 (CELF1) were more significantly associated with AD carrying APOE ɛ4, whereas rs1317149 (CELF1) showed an opposite trend. Interestingly, rs4147912 (ABCA7) and rs2516049 (HLA-DRB1) were identified to be relevant with AD carrying APOE ɛ4. Using expression quantitative trait locus analysis, we found polymorphisms in CELF1 (rs10742814 and rs11039280), ABCA7 (rs4147912), HLA-DRB1 (rs2516049), and ADGRF4 (rs1109581) correlated with their corresponding gene expression in the brain.ConclusionsWe identified four risk and four protective SNPs associated with AD in the Southern Chinese population, with different correlations between APOE ɛ4 carriers and non-carriers. rs4147912 (ABCA7) and rs2516049 (HLA-DRB1) were associated with AD carrying APOE ɛ4.

Project description:The Major Histocompatibility Complex (MHC, 6p21) codes for traditional HLA and other host response related genes. The polymorphic HLA-DRB1 gene in MHC Class II has been associated with several complex diseases. In this study we focus on MHC haplotype structures in the Finnish population. We explore the variability of extended HLA-DRB1 haplotypes in relation to the other traditional HLA genes and a selected group of MHC class III genes. A total of 150 healthy Finnish individuals were included in the study. Subjects were genotyped for HLA alleles (HLA-A, -B, -DRB1, -DQB1, and -DPB1). The polymorphism of TNF, LTA, C4, BTNL2 and HLA-DRA genes was studied with 74 SNPs (single nucleotide polymorphism). The C4A and C4B gene copy numbers and a 2-bp silencing insertion at exon 29 in C4A gene were analysed with quantitative genomic realtime-PCR. The allele frequencies for each locus were calculated and haplotypes were constructed using both the traditional HLA alleles and SNP blocks. The most frequent Finnish A∼B∼DR -haplotype, uncommon in elsewhere in Europe, was A*03∼B*35∼DRB1*01∶01. The second most common haplotype was a common European ancestral haplotype AH 8.1 (A*01∼B*08∼DRB1*03∶01). Extended haplotypes containing HLA-B, TNF block, C4 and HLA-DPB1 strongly increased the number of HLA-DRB1 haplotypes showing variability in the extended HLA-DRB1 haplotype structures. On the contrary, BTNL2 block and HLA-DQB1 were more conserved showing linkage with the HLA-DRB1 alleles. We show that the use of HLA-DRB1 haplotypes rather than single HLA-DRB1 alleles is advantageous when studying the polymorphisms and LD patters of the MHC region. For disease association studies the HLA-DRB1 haplotypes with various MHC markers allows us to cluster haplotypes with functionally important gene variants such as C4 deficiency and cytokines TNF and LTA, and provides hypotheses for further assessment. Our study corroborates the importance of studying population-specific MHC haplotypes.

Project description:Potential correlation of human papillomavirus (HPV) 16 E6 variants and human leukocyte antigen (HLA) class II polymorphisms has been suggested in patients with cervical cancer, so far little information is available about the possible interaction between E6 variants and HLA class II variability during the obviously accelerated progression to cervical cancer in young women. In this study, we aimed to explore the association between the HPV16 E6 variants and HLA-DRB1, DQB1 alleles in a Chinese young cervical cancer population. The HLA-DRB1, HLA-DQB1 polymophisms were genotyped by low-resolution polymerase chain reaction (PCR) with sequence-specific primer. HPV16 E6 DNA was tested by Sanger fluorescent dye dideoxy-termination technique. The difference of DRB1, DQB1 polymorphisms between young cervical cancer patients (≤35ys, n=61) and older ones (>35ys, n=85) and the association with E6 variants were analyzed. Results showed that the distribution pattern of HLA-DRB1, DQB1 alleles was different between young cervical cancer patients and older ones. The allele frequency of DQB1*0501 in young patients was significantly lower than older ones (6.6% vs. 23.5%, p<0.05). The HPV16 E6 A4 lineage was the exclusive type observed in young patients, and its prevalence was significantly higher than that of older cases (82.86% vs.41.94%, p<0.05). DRB1*03 was not found in young patients positive for the HPV16 E6 A4 lineage, whereas it was observed in 19.2 % older patients with A4 positive(Pc<0.05). In conclusion, specific association between certain HPV16 E6 variant and genetic polymorphisms of HLA may play a role during the progression of early onset cervical cancer in young patients. Certain HLA-DRB1 and HLA-DQB1 alleles may be related to the A4 lineage among young cervical cancer patients, which was the unique HPV16 E6 variant found in Chinese young patients. Our finding may provide an insight into the pathogenic factors that associated with cervical cancer in young women.

Dataset Information

Genetic Association of FERMT2, HLA-DRB1, CD2AP, and PTK2B Polymorphisms With Alzheimer's Disease Risk in the Southern Chinese Population.

Publications

Genetic Association of FERMT2, HLA-DRB1, CD2AP, and PTK2B Polymorphisms With Alzheimer's Disease Risk in the Southern Chinese Population.

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