CLOCK rs1801260 Polymorphism is Associated with Susceptibility to Parkinson's Disease in a Chinese Population.
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ABSTRACT:
SUBMITTER: Lou F
PROVIDER: S-EPMC5725382 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
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CLOCK rs1801260 Polymorphism is Associated with Susceptibility to Parkinson's Disease in a Chinese Population.
Lou Fan F Li Ming M Ren Yan Y Luo Xiao-Guang XG Liu Na N Li Xiaohong X
Neuroscience bulletin 20170805 6
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Project description:Immune disorders may play an important role in the pathogenesis of Parkinson's disease (PD). Recently, polymorphisms in the HLA-DR region have been found to be associated with sporadic PD in European ancestry populations. However, polymorphisms in the HLA complex are highly variable with ethnic and geographic origin. To explore the relationships between polymorphisms of the HLA-DR region and sporadic PD in Chinese Han population, we genotyped 567 sporadic PD patients and 746 healthy controls in two independent series for the HLA-DRB1 locus with Polymerase chain reaction-sequence based typing(PCR-SBT). The ?(2) test was used to evaluate the distribution of allele frequencies between the patients and healthy controls. The impact of HLA-DRB1 alleles on PD risk was estimated by unconditional logistic regression. We found a significant higher frequency of HLA-DRB1*0301 in sporadic PD patients than in healthy controls and a positive association, which was independent of onset age, between HLA-DRB1*0301 and PD risk. Conversely, a lower frequency of HLA-DRB1*0406 was found in sporadic PD patients than in healthy controls, with a negative association between HLA-DRB1*0406 and PD risk. Furthermore, a meta-analysis involving 195205 individuals was conducted to summarize the frequencies of these two alleles in populations from various ethnic regions, we found a higher frequency of HLA-DRB1*0301, but a lower frequency of HLA-DRB1*0406 in European ancestry populations than that in Asians, this was consistent with the higher prevalence of sporadic PD in European ancestry populations. Based on these results, we speculate that HLA-DRB1 alleles are associated with the susceptibility to sporadic PD in Chinese Han population, among them HLA-DRB1*0301 is a risk allele while the effect of HLA-DRB1*0406 deserves debate.
| S-EPMC3490875 | biostudies-literature
Project description:BACKGROUND: The cause of almost all cases of Parkinson's disease (PD) remains unknown. Recent years have seen an explosion in the rate of discovery of genetic defects linked to PD. Different racial and geographical populations may have different distributions of genetic variants. METHODS: In the current study, we screened the following genetic variants, including some rare mutations and single nucleotide polymorphisms (SNPs), in a pedigree and cases-controls. To best of our knowledge, we first screened these variants known to be associated with neurodegeneration disease, E46K (rs104893875) in SNCA, A1442P in LRRK2, IVS9 in PARK2, A350V in SLC41A1, P268S (rs2066842), R702W (rs2066844), G908R (rs2066845), 1007fs (rs2066847) in NOD2 and G2385R (rs34778348) in LRRK2 from southern China population. Genotyping was performed by jointly using primers overlapping polymerase chain reaction (PCR) site-directed mutagenesis, restriction fragment length polymorphism (RFLP), and capillary electrophoresis (CE). RESULTS: We didn't discover above 9 variants in the family members of the pedigree. Furthermore, of 237 patients with sporadic Parkinson's disease and 190 controls, no heterozygosity or homozygosity were found from E46K, A1442P, A350V, R702W, G908R, or 1007fs but heterozygosity onto G2385R, IVS9, and P268S. No significant difference between cases and controls was found in both allele frequency (P = 0.572) and genotype frequency (P = 0.348) of IVS9. However, significant differences in genotype frequency (P = 0.009) of G2385R were consistent with prior observation. Eight patients with Parkinson's disease (2 women and 6 men are over the age of 50 years at onset of PD) carried the P268S heterozygous variation in NOD2. There was no heterozygosity or homozygosity of P268S in the controls. Genotype frequency of P268S (P = 0.0450) had significant differences. CONCLUSIONS: Our results suggested that the P268S variant in NOD2 might be a risk factor for susceptibility to sporadic Parkinson's disease in Chinese populations. It also implied that the inflammatory response may play a role in PD.
| S-EPMC3662627 | biostudies-literature
Project description:PD is a complex disease, and may result from gene-gene and gene-environment interactions. There are limited studies on gene-gene interactions in PD. We and others have previously shown that SNCA rs356219, LRRK2 (rs2046932 and rs7304279) and GAK (rs1564282) are risk factors in sporadic PD. Since the expression of SNCA and neurotoxicity of alpha-synuclein are affected by LRRK2 and GAK, we hypothesize that their genetic risk variants may interact with each other. Here we investigated the interaction of SNCA rs356219, LRRK2rs7304279 and rs2046932 and GAK rs1564282 using the Multifactor Dimensionality Reduction (MDR) in a Chinese PD patient-control series (534 patients and 435 controls) and the cumulative risk effect of SNCA, LRRK2 and GAK. The MDR analysis showed a significant gene-gene interaction between the rs356219 of SNCA, rs2046932 of LRRK2 and rs1564282 of GAK. Moreover, individuals with increasing numbers of variants had an increasing likelihood of having PD, compared with those carrying none of the variants. The estimated OR for developing PD in individuals carrying 3 variants was 5.89. We demonstrated for the first time that SNPs in SNCA, LRRK2 and GAK interacted with each other to confer an increased risk of PD. In addition, PD risk increased cumulatively with the increasing number of variants.
| S-EPMC5820994 | biostudies-other
Project description:PurposeThere is growing evidence that autophagy-related gene 5 (ATG5) is involved in neural development, neuronal differentiation, and neurodegenerative diseases. The purpose of this study was to investigate the association between ATG5 gene single-nucleotide polymorphisms (SNPs) and Parkinson's disease (PD) in the Han population.MethodsA case-control study was conducted in 120 PD patients and 100 healthy volunteers. MassArray platform was used to analyze polymorphisms in three different regions of ATG5 gene (rs510432, rs573775 and rs17587319). In the included subjects, 50 PD patients and 50 healthy volunteers were selected, and the plasma ATG5 concentration was detected by enzyme-linked immunosorbent assay (ELISA). The allele and genotype frequencies of SNPs were assessed using the SHEsis program.ResultsWe found a significant correlation between rs17587319 and PD, and the subcomponent showed a high correlation between rs17587319 with cognitive impairment and age at onset in PD patients. At the same time, the total plasma ATG5 level of PD patients and the plasma ATG5 expression level of early-onset Parkinson's disease (EOPD) patients were significantly higher than the control group, while there was no significant difference of ATG5 expression between late-onset Parkinson's disease (LOPD) patients and the control group.ConclusionThese findings suggest that genetic variations in the ATG5 gene and low levels of the ATG5 protein are associated with susceptibility to PD and with cognitive impairment in PD patients. ATG5 could be a potential biomarker to assess the severity and prognosis of PD.
| S-EPMC9300489 | biostudies-literature
Project description:BackgroundKawasaki disease (KD) is a multisystem vasculitis in infants and young children and involved in the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome activation. Genetic factors may increase the risk of KD. To assess the association between rs7248320 in long noncoding RNA (lncRNA) AC008392.1 located in the upstream region of CARD8 and the risk of KD, a case-control study was conducted in the Han Chinese population.MethodsThis study genotyped the polymorphism rs7248320 in the lncRNA AC008392.1 gene using the TaqMan real-time polymerase chain reaction assay. The genetic contribution of rs7248320 was evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. The association between rs7248320 and KD susceptibility was analyzed by performing a hospital-based case-control study including 559 KD patients and 1055 non-KD controls.ResultsIn this study, a significant relationship between rs7248320 and KD risk was observed in the genotype/allele frequency distribution. The rs7248320 polymorphism was associated with a significantly decreased risk of KD after adjustment for age and sex (AG vs AA: adjusted OR = 0.80, 95% CI: 0.64-0.99, P = 0.0421; GG vs AA: adjusted OR = 0.71, 95% CI: 0.51-1.00, P = 0.0492; AG/GG vs AA: adjusted OR = 0.78, 95% CI: 0.63-0.96, P = 0.0186). Moreover, the rs7248320 G allele also exhibited a decreased risk for KD (adjusted OR = 0.83, 95% CI: 0.72-0.97, P = 0.0193) compared with the A allele. In the stratification analysis, compared to the rs7248320 AA genotype, AG/GG genotypes were more protective for males (OR = 0.71, 95% CI: 0.55-0.93, P = 0.0122).ConclusionThis study suggests for the first time that the lncRNA AC008392.1 rs7248320 polymorphism may be involved in KD susceptibility in the Han Chinese population.
| S-EPMC8464376 | biostudies-literature
Project description:BackgroundThe fat mass and obesity-associated protein (FTO) has been showed to be involved in the pathogenesis and progression of coronary artery disease (CAD). However, the effects of FTO variants on CAD risk remain poorly understood. We herein genotyped three SNPs (rs1121980, rs72803657, and rs4783818) in FTO to investigate the influence of FTO polymorphisms on individual susceptibility to CAD.MethodsGenotyping for the three SNPs (rs1121980, rs72803657, and rs4783818) was conducted in a cohort of 712 CAD cases with 349 myocardial infarction (MI) cases and 701 control participants, utilizing the polymerase chain reaction-ligation detection reaction (PCR-LDR) technique. The associations of these SNPs with CAD were analyzed using multivariate logistic regression, and the associations with lipid profiles were assessed by the Kruskal-Wallis or Wilcoxon-Mann-Whitney tests.ResultsThe A allele (OR = 1.26, 95% CI = 1.01-1.57, and P = 0.044) and the AA genotype (OR = 3.13, 95% CI = 1.53-6.38, and P = 0.002) of FTO rs1121980 were significantly associated with an elevated risk of CAD. Similarly, the A allele (OR = 1.54, 95% CI = 1.18-2.02, and P = 0.002) and the AA genotype (OR = 5.61, 95% CI = 2.57-12.27, and P < 0.001) of rs1121980 exhibited increased MI risk. This SNP also showed significant associations under recessive genetic models for both CAD and MI (OR = 3.09, 95% CI = 1.52-6.27, P = 0.002 for CAD; OR = 5.40, 95% CI = 2.49-11.71, P < 0.001 for MI). However, the other two SNPs did not show significant associations with CAD or MI risks under any genetic model tested. Stratified analyses indicated a more pronounced association of the A allele with increased CAD/MI risk among younger participants, non-smokers, and non-drinkers. Interestingly, A allele carriers in younger subjects exhibited higher triglyceride (TG) levels and lower high-density lipoprotein cholesterol (HDL-C) levels compared to non-carriers (P < 0.05).ConclusionsOur data provides the first evidence that the FTO rs1121980 polymorphism is associated with an increased risk of CAD in the Chinese population. This association is more significant in younger subjects, likely due to the elevated TG levels and reduced HDL-C levels.
| S-EPMC11697032 | biostudies-literature
Project description:To find a new locus that confers significant susceptibility to CAD in Chinese Han population, a genome-wide association study in 200 "extreme individuals" from a Shandong cohort and a pathway-based candidate gene study from a Shanghai cohort (293 CAD/293 controls) were simultaneously performed. Amongst them, 13 SNPs associated with CAD were selected to conduct validation and replication studies in additional 3363 CAD patients and 3148 controls. A novel locus rs700926 in natriuretic peptide receptor C (NPR-C) was identified in Shandong and Hubei cohorts. Then rs700926 and other nine tag SNPs were genotyped in four geographically different populations (Shandong, Shaanxi, Hubei and Sichuan cohorts), and 6 SNPs (rs700926, rs1833529, rs2270915, rs17541471, rs3792758 and rs696831) showed stronger association with CAD, regardless of single or combined analysis. We further genotyped rs2270915 and 10 additional tag SNPs in a central China cohort and identified rs12697273 and rs10066436 as the loci associated with CAD. All these positive associations remained significant after adjustment for traditional risk factors of CAD. NPR-C gene SNPs significantly contribute to CAD susceptibility in the Chinese Han population.
| S-EPMC5085110 | biostudies-literature
Project description:BackgroundAccumulating evidence has demonstrated that the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a part of Lewy body inclusions and involves the pathogenesis of Parkinson's disease (PD). However, it remains unknown whether or not genetic variation at the GAPDH locus contributes to the risk for PD.MethodsA total of 302 sporadic PD patients and 377 control subjects were recruited in our study for assessing two single nucleotide polymorphisms (rs3741918 and rs1060619) in the GAPDH gene. Both allelic association and additive models were used to analyze association between GAPDH variants and risk for PD.ResultsBoth polymorphisms were significantly associated with risk for PD after correction by Bonferroni multiple testing. The minor allele of rs3741918 was associated with decreased risk of sporadic PD (allelic contrast, OR = 0.74, 95% CI: 0.59-0.93, corrected P = 0.028; additive model, OR = 0.73, 95% CI: 0.58-0.92, corrected P = 0.018). While for the rs1060619 locus, the minor allele conferred increased risk for PD (allelic contrast, OR = 1.41, 95% CI: 1.14-1.75, corrected P = 0.007; additive model, OR = 1.43, 95% CI: 1.15-1.79, corrected P = 0.002).ConclusionOur study indicates that GAPDH variants confer susceptibility to sporadic PD in a Chinese Han population, which is consistent with the role of GAPDH protein in neuronal apoptosis. To our knowledge, this is the first study of genetic association between GAPDH locus and risk for PD in the Chinese population.
| S-EPMC4530932 | biostudies-literature
Project description:PD is a complex disease, and may result from gene-gene and gene-environment interactions. There are limited studies on gene-gene interactions in PD. We and others have previously shown that SNCA rs356219, LRRK2 (rs2046932 and rs7304279) and GAK (rs1564282) are risk factors in sporadic PD. Since the expression of SNCA and neurotoxicity of alpha-synuclein are affected by LRRK2 and GAK, we hypothesize that their genetic risk variants may interact with each other. Here we investigated the interaction of SNCA rs356219, LRRK2rs7304279 and rs2046932 and GAK rs1564282 using the Multifactor Dimensionality Reduction (MDR) in a Chinese PD patient-control series (534 patients and 435 controls) and the cumulative risk effect of SNCA, LRRK2 and GAK. The MDR analysis showed a significant gene-gene interaction between the rs356219 of SNCA, rs2046932 of LRRK2 and rs1564282 of GAK. Moreover, individuals with increasing numbers of variants had an increasing likelihood of having PD, compared with those carrying none of the variants. The estimated OR for developing PD in individuals carrying 3 variants was 5.89. We demonstrated for the first time that SNPs in SNCA, LRRK2 and GAK interacted with each other to confer an increased risk of PD. In addition, PD risk increased cumulatively with the increasing number of variants.
| S-EPMC5852682 | biostudies-literature
Project description:ObjectiveIntrahepatic cholangiocarcinoma is a rare disease whose etiology is far from clear, the Ser326Cys polymorphism in human 8-hydroxyguanine glycosylase (hOGG1) has been shown associated with various cancers, however, the association of Ser326Cys (rsl052133) polymorphism and intrahepatic cholangiocarcinoma susceptibility has not been clarified. The purpose of this study is to investigate whether this polymorphism is related to the genetic susceptibility of intrahepatic cholangiocarcinoma.MethodsA total 150 patients and 150 normal people were included in this study, the Ser326Cys polymorphisms in each group were genotyped using PCR-RFLP method.ResultsWe found that individuals carrying Cys/Cys genotype were exposed to higher riskof intrahepatic cholangiocarcinoma (OR=2.924, 95% CI=1.475-5.780) compared with the individuals with wild type genotype Ser/Ser. Further analysis revealed that male individuals carrying Cys/Cys genotype also had increased risk (OR=2.762, 95% CI=1.233-6.173), whereas no significant difference was observed in female group.ConclusionsTherefore, our data indicates that the Ser326Cys (rs1052133) polymorphism is associated with intrahepatic cholangiocarcinoma susceptibility, and it shows preference in male population.
| S-EPMC4659035 | biostudies-literature