S100B gene polymorphisms are associated with the S100B level and Alzheimer's disease risk by altering the miRNA binding capacity.
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ABSTRACT:
SUBMITTER: Wang J
PROVIDER: S-EPMC8202836 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The levels of serum S100B were elevated in patients with ischemic stroke (IS), which may be a novel biomarker for diagnosing IS. The aim of this study was to investigate the association of S100B polymorphisms and serum S100B with IS risk. We genotyped the S100B polymorphisms rs9722, rs9984765, rs2839356, rs1051169 and rs2186358 in 396 IS patients and 398 controls using polymerase chain reaction-single base extension (SBE-PCR). Serum S100B levels were measured by enzyme-linked immunosorbent assay (ELISA). Rs9722 was associated with an increased risk of IS (AA vs. GG: adjusted OR = 2.172, 95% CI, 1.175-4.014, P = 0.013; dominant: adjusted OR = 1.507, 95% CI, 1.071-2.123, P = 0.019; recessive: adjusted OR = 1.846, 95% CI, 1.025-3.323, P = 0.041; additive: adjusted OR=1.371, 95% CI, 1.109-1.694, P = 0.003). The A-C-C-C-A haplotype was associated with an increased risk of IS (OR = 1.325, 95% CI, 1.035-1.696, P = 0.025). In addition, individuals carrying the rs9722 GA/AA genotypes had a higher serum S100B compared with the rs9722 GG genotype in IS patients (P = 0.018). Our results suggest that the S100B gene rs9722 polymorphism may contribute to the susceptibility of IS, probably by promoting the expression of serum S100B.
| S-EPMC5772371 | biostudies-literature
Project description:The aim of this study was to investigate whether the S100B polymorphisms are associated with systemic lupus erythematous (SLE) in a Chinese population. A total of 313 SLE patients and 396 control subjects were enrolled in the present study. The genotypes of three SNPs (rs9722, rs881827 and rs1051169) in S100B gene were detected by single base extension polymerase chain reaction (SBE-PCR). Serum S100B levels were determined by enzyme-linked immunosorbent assay (ELISA). Rs1051169 was associated with an increased risk of SLE (C vs. G: adjusted OR=1.46, 95% CI, 1.18-1.80, p=0.001; CC vs. GG: adjusted OR=1.99, 95% CI, 1.32-3.02, p=0.001; CC+GC vs. GG: adjusted OR=1.54, 95% CI, 1.13-2.11, p=0.007; CC vs. GC+GG: adjusted OR=1.67, 95% CI, 1.16-2.42, p=0.006). Haplotype analysis showed that the G-G-C haplotype was associated with an increased risk of SLE (OR=1.50, 95% CI, 1.14-1.98, p=0.004). Stratified analyses showed that the rs1051169 polymorphism was associated with an increased risk of neurologic disorder in SLE patients (C vs. G: OR=1.78, 95% CI, 1.22-2.59, p=0.003; GC vs. GG: OR=2.33, 95% CI, 1.14-4.77, P=0.019; CC vs. GG: OR=3.02, 95% CI, 1.39-6.53, p=0.004; CC+GC vs. GG: OR=2.57, 95% CI=1.31-5.04, p=0.005). In addition, SLE patients with neurologic disorder carrying the rs1051169 GC/CC genotypes present a higher serum S100B levels compared with that carrying the GG genotype (p < 0.05). Our results indicate that the rs1051169 polymorphism may be involved in the pathogenesis of SLE.
| S-EPMC6726149 | biostudies-literature
Project description:BACKGROUND: Numerous single nucleotide polymorphisms (SNPs) associated with complex diseases have been identified by genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) studies. However, few of these SNPs have explicit biological functions. Recent studies indicated that the SNPs within the 3'UTR regions of susceptibility genes could affect complex traits/diseases by affecting the function of miRNAs. These 3'UTR SNPs are functional candidates and therefore of interest to GWAS and eQTL researchers. DESCRIPTION: We developed a publicly available online database, MirSNP (http://cmbi.bjmu.edu.cn/mirsnp), which is a collection of human SNPs in predicted miRNA-mRNA binding sites. We identified 414,510 SNPs that might affect miRNA-mRNA binding. Annotations were added to these SNPs to predict whether a SNP within the target site would decrease/break or enhance/create an miRNA-mRNA binding site. By applying MirSNP database to three brain eQTL data sets, we identified four unreported SNPs (rs3087822, rs13042, rs1058381, and rs1058398), which might affect miRNA binding and thus affect the expression of their host genes in the brain. We also applied the MirSNP database to our GWAS for schizophrenia: seven predicted miRNA-related SNPs (p?<?0.0001) were found in the schizophrenia GWAS. Our findings identified the possible functions of these SNP loci, and provide the basis for subsequent functional research. CONCLUSION: MirSNP could identify the putative miRNA-related SNPs from GWAS and eQTLs researches and provide the direction for subsequent functional researches.
| S-EPMC3582533 | biostudies-literature
Project description:MicroRNAs (miRNAs) regulate posttranscriptional gene expression usually by binding to 3'-untranslated regions (3'-UTRs) of target message RNAs (mRNAs). Hence genetic polymorphisms on 3'-UTRs of mRNAs may alter binding affinity between miRNAs target 3'-UTRs, thereby altering translational regulation of target mRNAs and/or degradation of mRNAs, leading to differential protein expression of target genes. Based on a database that catalogues predicted polymorphisms in miRNA target sites (poly-miRTSs), we selected 568 polymorphisms within 3'-UTRs of target mRNAs and performed association analyses between these selected poly-miRTSs and osteoporosis in 997 white subjects who were genotyped by Affymetrix Human Mapping 500K arrays. Initial discovery (in the 997 subjects) and replication (in 1728 white subjects) association analyses identified three poly-miRTSs (rs6854081, rs1048201, and rs7683093) in the fibroblast growth factor 2 (FGF2) gene that were significantly associated with femoral neck bone mineral density (BMD). These three poly-miRTSs serve as potential binding sites for 9 miRNAs (eg, miR-146a and miR-146b). Further gene expression analyses demonstrated that the FGF2 gene was differentially expressed between subjects with high versus low BMD in three independent sample sets. Our initial and replicate association studies and subsequent gene expression analyses support the conclusion that these three polymorphisms of the FGF2 gene may contribute to susceptibility to osteoporosis, most likely through their effects on altered binding affinity for specific miRNAs.
| S-EPMC3179316 | biostudies-literature
Project description:Background: Aquaporin 4 (AQP4) polymorphism may influence the required dosage of antipsychotic drugs. However, the roles of AQP4 polymorphisms in the blood-brain barrier (BBB) and different neuroprotective effects need further exploration. This study aims to investigate whether the gene polymorphisms and haplotype of AQP4 are associated with serum S100 calcium-binding protein B (S100B) level and clinical symptoms in patients with schizophrenia (SCZ). Methods: We recruited 190 patients with SCZ. They provided demographic data, completed relevant questionnaires, and submitted samples to test for four AQP4 tag single nucleotide polymorphisms (SNPs) and eight haplotypes. The rating scales of Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP), the Global Assessment of Functioning (GAF), Clinical Global Impression (CGI) were assessed and serum S100B level were measured repeatedly during antipsychotic treatment at weeks 0 (baseline), 3, 6, and 9. Using generalized estimating equation (GEE) analyses, log-transformed S100B (logS100B) level was tested for associations with haplotype and other dependent variables. Results: Discretization via the median split procedure showed that logS100B level >1.78 or ? 1.78 had the best discriminant validity to stratify the patients into two groups. After 9 weeks of treatment, the serum S100B level was decreased. The TAA haplotype of AQP4 SNPs was associated with increased serum S100B level (p = 0.006). The PANSS negative subscale (PANSS-N) (p = 0.001) and Clinical Global Impression-Improvement (CGI-I) (p = 0.003) scores had a positive association with S100B level. Conclusion: Patients with the TAA haplotype of the AQP4 polymorphism are likely to have increased serum S100B level, negative symptoms and poor control of neuroinflammation. A logS100B level >1.78 may be sufficiently specific to predict a higher severity of negative symptoms. Further study including healthy controls and patients with first and recurrent episodes under selective AQP4 modulators will be necessary to explore the profound effects on the treatment of patients with SCZ and may positively influence their overall outcome.
| S-EPMC6297372 | biostudies-literature
Project description:BackgroundRNA interference is a gene regulatory mechanism that employs small RNA molecules such as microRNA. Previous work has shown that HIV-1 produces TAR viral microRNA. Here we describe the effects of the HIV-1 TAR derived microRNA on cellular gene expression.ResultsUsing a variation of standard techniques we have cloned and sequenced both the 5' and 3' arms of the TAR miRNA. We show that expression of the TAR microRNA protects infected cells from apoptosis and acts by down-regulating cellular genes involved in apoptosis. Specifically, the microRNA down-regulates ERCC1 and IER3, protecting the cell from apoptosis. Comparison to our cloned sequence reveals possible target sites for the TAR miRNA as well.ConclusionThe TAR microRNA is expressed in all stages of the viral life cycle, can be detected in latently infected cells, and represents a mechanism wherein the virus extends the life of the infected cell for the purpose of increasing viral replication.
| S-EPMC2654423 | biostudies-literature
Project description:Genome-wide association studies are identifying novel Alzheimer's disease (AD) risk factors. Elucidating the mechanism underlying these polymorphisms is critical to the validation process and, by identifying rate-limiting steps in AD risk, may yield novel therapeutic targets. Here, we elucidate the mechanism of action of the AD-associated polymorphism rs3865444 in the promoter of CD33, a member of the sialic acid-binding Ig-superfamily of lectins (SIGLECs). Immunostaining established that CD33 is expressed in microglia in human brain. Consistent with this finding, CD33 mRNA expression correlated well with expression of the microglial genes CD11b and AIF-1 and was modestly increased with AD status and the rs3865444C AD-risk allele. Analysis of CD33 isoforms identified a common isoform lacking exon 2 (D2-CD33). The proportion of CD33 expressed as D2-CD33 correlated robustly with rs3865444 genotype. Because rs3865444 is in the CD33 promoter region, we sought the functional polymorphism by sequencing CD33 from the promoter through exon 4. We identified a single polymorphism that is coinherited with rs3865444, i.e., rs12459419 in exon 2. Minigene RNA splicing studies in BV2 microglial cells established that rs12459419 is a functional single nucleotide polymorphism (SNP) that modulates exon 2 splicing efficiency. Thus, our primary findings are that CD33 is a microglial mRNA and that rs3865444 is a proxy SNP for rs12459419 that modulates CD33 exon 2 splicing. Exon 2 encodes the CD33 IgV domain that typically mediates sialic acid binding in SIGLEC family members. In summary, these results suggest a novel model wherein SNP-modulated RNA splicing modulates CD33 function and, thereby, AD risk.
| S-EPMC3742922 | biostudies-literature
Project description:ObjectivesNeprilysin (NEP) is an amyloid beta-peptide (Abeta) degrading enzyme expressed in the brain, and accumulation of Abeta is the neuropathological hallmark in Alzheimer's disease (AD). In this study we investigated whether polymorphisms in the NEP gene have an effect on the risk for AD.MethodsThe frequencies of seven single nucleotide polymorphisms (SNPs) and apolipoprotein E (APOE) were assessed in 390 AD patients and 468 cognitively healthy controls. Genotypes of the study groups were compared using binary logistic regression analysis. Haplotype frequencies of the SNPs were estimated from genotype data.ResultsTwo SNPs, rs989692 and rs3736187, had significantly different allelic and genotypic frequencies (uncorrected p = 0.01) between the AD and the control subjects and haplotype analysis showed significant association between AD and NEP polymorphisms.ConclusionTaken together, these findings suggest that polymorphisms in the NEP gene increase risk for AD and support a potential role for NEP in AD.
| S-EPMC1738829 | biostudies-literature
Project description:Interleukin (IL) 16 plays a key role in inflammatory diseases as well as in tumorigenesis of osteosarcoma (OS). The aim of this study was to investigate the association of IL16 polymorphisms and plasma IL16 level with OS risk in a Chinese population. We genotyped IL16 rs4778889, rs11556218, and rs4072111 in 358 patients with OS and 402 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. Plasma IL16 level was measured by enzyme-linked immunosorbent assay. Rs11556218 was associated with an increased risk of OS in heterozygote comparison (adjusted OR = 1.65, 95% CI, 1.23-2.21, P < 0.001), dominant model (adjusted OR = 1.66, 95% CI, 1.24-2.21, P < 0.001), and allele comparison (adjusted OR = 1.44, 95% CI, 1.14-1.81, P = 0.002). Moreover, rs11556218 TG/GG genotypes were associated with higher levels of IL16 as compared to TT genotype (P = 0.03). However, no significant association of rs4778889 and rs4072111 and OS was found. These findings suggest that rs11556218 TG/GG genotypes may be associated with increased susceptibility to OS, probably by increasing the production of IL16 level.
| S-EPMC5050415 | biostudies-literature
Project description:A coding missense mutation (rs3747742) in triggering receptor expressed on myeloid cell-like 2 (TREML2) has been recently proposed as an important protective factor against Alzheimer's disease (AD). However, the link between TREML2 and AD pathology remains unclear. Therefore, we explored the association of TREML2 rs3747742 with cognitive function, neuroimaging biomarkers and cerebrospinal fluid (CSF) biomarkers related to AD, including CSF total-tau (T-tau), phosphor-tau (P-tau), and amyloid-β (Aβ1-42). As for cognitive function, related cognitive scores of Clinical Dementia Rating Sum of Boxes (CDRSB), Alzheimer's Disease Assessment Scale-cognitive section 11 (ADAS-cog 11), Mini-Mental State Examination (MMSE), and Rey Auditory-Verbal Learning Test (RAVLT) were extracted. We used a multiple linear regression model to examine the association of TREML2 rs3747742 with the baseline variables. Furthermore, we also calculated the change rate of above variables influenced by TREML2 rs3747742 via applying a mixed-effects model over a 4-year follow-up. In this analysis, a total of 1,306 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. Finally, we observed that only in AD patients, but not in normal controls or mild cognitive impairment (MCI) individuals, TREML2 rs3747742 exhibited a strong association with CSF total-tau levels at baseline (β = -22.1210, p = 0.0166) and 4-year follow-up (β = -0.3961, p = 0.0115). Furthermore, no associations were found with CSF Aβ1-42 levels, P-tau levels, neuroimaging biomarkers and cognitive function neither for baseline variables nor for longitudinal data. Thus, this study indicated that TREML2 mediated the risk of AD through influencing AD-related neurodegeneration (abnormal T-tau levels) but not P-tau levels and Aβ pathology.
| S-EPMC6529571 | biostudies-literature