Project description:BackgroundSeveral case-control studies reported the relationship between single nucleotide polymorphisms (SNPs) in HSP70 genes and noise-induced hearing loss (NIHL). However, their conclusions are conflicting. This meta-analysis aims to identify the association of HSP70 variants and NIHL susceptibility.MethodA systematical literature search was performed in PubMed, Web of Science, EMBASE, and Wanfang Chinese database. The pooled odds radio (OR), 95% confidence interval (CI) and p value were calculated in fixed- or random-effects model according to the I2 value in the heterogeneity test.ResultsFour articles containing five studies, including 633 cases and 926 controls, were included. Under the allele, homozygote and dominant model, the pooled ORs (95%CI, p-value) of rs1061581 were 1.32 (1.06-1.67, p = 0.019), 1.93 (1.10-3.36, p = 0.021) and 1.455 (1.408-2.019, p = 0.025), respectively. In addition, a significant association was found between rs2227956 in Caucasians and the NIHL susceptibility under all five genetic models. We did not discover evidence sufficient to prove the associations between the other three SNPs (rs1043618, rs2763979 and rs2075800) and the NIHL susceptibility.ConclusionThis meta-analysis indicated that the two HSP70 variants, rs1061581 and rs2227956, may serve as genetic susceptibility factors for NIHL. Larger scale studies are required to further update the results.
Project description:BackgroundRecent studies have evaluated the associations between polymorphisms of the heat-shock protein 70 (HSP70) encoding genes and noise-induced hearing loss (NIHL). However, the conclusions of these studies are conflicting. The objective of this meta-analysis was to clarify the association between all known polymorphisms of HSP70 genetic loci and susceptibility to NIHL, based on existing reports.MethodsWe conducted a meta-analysis of the association between Hsp70 polymorphisms (rs1043618, rs1061581, rs2075800, rs2227956, and rs2763979) and NIHL risk in both Chinese and Caucasian males. All statistical analysis was done with was conducted using the "meta" package (version 4.6-0) of R version 3.3.2 and RStudio version 1.0.44. Online databases were searched for eligible case-control studies on February 13, 2017. The odds ratio (OR), 95% confidence interval (CI), and P value were calculated using Mantel-Haenszel statistics under a random- or fixed-effect model.ResultsA total of five studies, reported via four articles from online databases, were included in our meta-analysis. For rs1061581 (from three studies), a significant association was detected in the allele model, homozygote model, and dominant model (G versus A: OR (95% CI) = 1.32(1.05-1.67), GG versus AA: OR (95% CI) = 1.93(1.1-3.36), GG + AG versus AA: OR (95% CI) = 1.45(1.05-2.02)), but not in the heterozygote model or the recessive model. For rs1043618 (from five studies), rs2075800 (from two studies), rs2227956 (from four studies), rs2763979 (from two studies), no significant association was found for any genetic model. After subgroup analyses by ethnicity, significant associations were observed for the allele model, heterozygote model, and dominant model for rs1061581 and any genetic model for rs2227956 in Caucasians.ConclusionsThe rs1043618, rs2075800, and rs2763979 polymorphisms were not found to be associated with susceptibility to NIHL; however, the rs1061581 and rs2227956 polymorphisms were significantly associated with NIHL in Caucasian males.
Project description:Noise-induced hearing loss (NIHL) is the second-most frequent form of sensorineural hearing loss. When exposed to the same noise, some workers develop NIHL while others do not, suggesting that NIHL may be associated with genetic factors. To explore the relationship between single nucleotide polymorphisms (SNPs) in heat shock protein 70 (HSP70) genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility to NIHL in Han Chinese workers exposed to noise, a case-control association study was carried out with 286 hearing loss cases and 286 matched with gender, age, type of work, and exposure time, drawn from a population of 3790 noise-exposed workers. Four SNPs were selected and genotyped. Subsequently, the effects of the alleles and genotypes of the three HSP70 genes (HSPA1A, HSPA1B and HSPA1L) on NIHL were analyzed by using a conditional logistic regression. A generalized multiple dimensionality reduction (GMDR) was applied to further detect an interaction between the four SNPs. Compared with the combined genotypes CC/TC, carriers of the TT genotype of rs2763979 appeared to show greater susceptibility to NIHL (P = 0.042, adjusted OR = 1.731, 95% CI 1.021-2.935). A significant interaction between rs2763979 and CNE was found (P = 0.029), and a significant association was found between TT of s2763979 and NIHL (P = 0.024, adjusted OR = 5.694, 95%CI 1.256-25.817) in the 96 dB (A)≤CNE<101 dB (A) group. The results suggest that the rs2763979 locus of the HSP70 genes may be associated with susceptibility to NIHL in Chinese individuals, and other HSP70 genes may also be susceptibility genes for NIHL, but the results must be further replicated in additional independent sample sets.
Project description:IntroductionHeat shock proteins (HSPs) protect cells under adverse conditions such as infection, inflammation, and disease. The differential expression of HSPs in human periapical granulomas suggests a potential role for these proteins in periapical lesion development, which may contribute to different clinical outcomes. Therefore, we hypothesized that polymorphisms in HSP genes leading to perturbed gene expression and protein function may contribute to an individual's susceptibility to periapical lesion development.MethodsSubjects with deep carious lesions with or without periapical lesions (≥3 mm) were recruited at the University of Texas School of Dentistry at Houston and at the University of Pittsburgh. Genomic DNA samples of 400 patients were sorted into 2 groups: 183 cases with deep carious lesions and periapical lesions (cases) and 217 cases with deep carious lesions but without periapical lesions (controls). Eight single nucleotide polymorphisms (SNPs) in HSPA4, HSPA6, HSPA1L, HSPA4L, and HSPA9 genes were selected for genotyping. Genotypes were generated by end point analysis by using Taqman chemistry in a real-time polymerase chain reaction assay. Allele and genotype frequencies were compared among cases and controls by using χ(2) and Fisher exact tests as implemented in PLINK v.1.07. In silico analysis of SNP function was performed by using Polymorphism Phenotyping V2 and MirSNP software.ResultsOverall, SNPs in HSPA1L and HSPA6 showed significant allelic association with cases of deep caries and periapical lesions (P < .05). We also observed altered transmission of HSPA1L SNP haplotypes (P = .03). In silico analysis of HSPA1L rs2075800 function showed that this SNP results in a glutamine-to-lysine substitution at position 602 of the protein and might affect the stability and function of the final protein.ConclusionsVariations in HSPA1L and HSPA6 may be associated with periapical lesion formation in individuals with untreated deep carious lesions. Future studies could help predict host susceptibility to developing apical periodontitis.
Project description:BackgroundNoise-induced hearing loss (NIHL) is a complex disease induced by a combination of genetic and environmental factors. Paraoxonase2 (PON2) gene involved in the regulation of reactive oxygen species, and affecting the vulnerability of cochlea to NIHL, and ATPase, calcium-transporting, plasma membrane 2 (ATP2B2) gene which encodes plasma membrane calcium-transporting ATPase isoform 2 (PMCA2) are the candidate genes relating to the attack of NIHL. In this study, we investigated whether ATP2B2 and PON2 polymorphisms were associated with NIHL in Chinese of Han nationality population.MethodsWe performed a case-control study between six single nucleotide polymorphisms (SNPs) (rs1719571, rs3209637 and rs4327369 within ATP2B2, rs12026, rs7785846 and rs12704796 within PON2) and NIHL in 454 subjects. All the SNPs were genotypes, using the TaqMan MGB probe assay. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs) with logistic regression analysis to test the level of association for SNPs.ResultsIn our study, 221 subjects with hearing loss and 233 subjects without hearing loss were recruited. The frequencies of the CG and CG + GG genotype of rs12026 (PON2) conferred risk factors for NIHL with adjusted OR values of 2.62 (95% CI, 1.69-4.06) and 2.48 (95% CI, 1.63-3.78), respectively. This kind of significance was also found at locus rs7785846, where genotypes CT and CT + TT were the risk types, with adjusted ORs of 2.52 (95% CI, 1.62-3.93) and 2.35 (95% CI, 1.54-3.58), respectively. We performed stratified analysis per noise exposure level, when it came to rs7785846 and rs12026 in the >92 dB(A) noise exposure group, the subjects who carried heterozygote were of significantly (P<0.01) higher susceptibility to NIHL than homozygote carriers. By contrast, no significantly higher risk was found for any rs12704796 genotypes or any genotypes in ATP2B2 (P>0.05), which may suggest that these SNPs did not have significant effects on noise susceptibility across noise exposure.ConclusionsOur research suggested that PON2 might play a role in the etiology of NIHL in Chinese of Han nationality population.
Project description:The 70-kDa heat shock protein (Hsp) family is composed of both environmentally inducible (Hsp) and constitutively expressed (Hsc) family members. We sequenced 2 genes encoding an Hsp70 and an Hsc70 in the Pacific oyster Crassostrea gigas. The Cghsc70 gene contained introns, whereas the Cghsp70 gene did not. Moreover, the corresponding amino acid sequences of the 2 genes presented all the characteristic motifs of the Hsp70 family. We also investigated the expression of Hsp70 in tissues of oysters experimentally exposed to metal. A recombinant Hsc72 was used as an antigen to produce a polyclonal antibody to quantify soluble Hsp70 by enzyme-linked immunosorbent assay in protein samples extracted from oysters. Our results showed that metals (copper and cadmium) induced a decrease in cytosolic Hsp70 level in gills and digestive gland of oysters experimentally exposed to metal. These data suggest that metals may inhibit stress protein synthesis.
Project description:ObjectiveTo explore the association of lifestyles, caspase gene (CASP), and noise kurtosis with noise-induced hearing loss (NIHL).DesignThree hundred seven NIHL individuals and 307 matched controls from factories in Chinese factories participated in this case-control study. Age, sex, noise exposure, exfoliated oral mucosa cells, and lifestyles of participants were gathered by the authors. The single nucleotide polymorphisms (SNPs) were genotyped using the Kompetitive Allele Specific polymerase chain reaction (KASP) method.ResultsThe risk of NIHL was higher for people who worked in the complex noise environment than for people exposed to steady noise environment (adjusted: OR = 1.806, P = 0.002). Smoking and regular earphone use increased the risk of NIHL (adjusted: OR = 1.486, P = 0.038). The GG genotype of the recessive model and G allele in rs1049216, together with the TT genotype of the recessive model in rs6948 decreased the NIHL risk (adjusted: OR = 0.659, P = 0.017). Oppositely, the AA genotype of additive model in rs12415607 had a higher NIHL risk (adjusted: OR = 1.804, P = 0.024). In the additive models, there was a positive interaction between noise kurtosis and CASP3 polymorphisms (RERI = 1.294, P = 0.013; RERI = 1.198, P = 0.031).ConclusionsNoise kurtosis, three SNPs (rs1049216, rs6948, and rs12415607), smoking and earphone use were found to be related to NIHL, and there was a positive interaction between noise kurtosis and CASP3. Results from this study can be used to prevent and detect NIHL and for genetic testing.
Project description:We evaluated the heat shock system 70 (HSP70) in patients with chronic glomerulonephritis (CGN). Seventy-six patients with CGN patients were included in our study. Ten patients with mild proteinuria (median 0.48 [0.16-0.78] g/24 h) and ten healthy subjects served as positive and negative controls, respectively. Urinary levels of HSP70, interleukin-10, and serum levels of anti-HSP70 were measured by ELISA. The immunohistochemical peroxidase method was used to study the expression of HSP70 and Foxp3+ in kidney biopsies. TregFoxP3+ cells in the interstitium were determined morphometrically. Median urinary HSP70 levels in patients with nephrotic syndrome (NS) [6.57 (4.49-8.33) pg/mg] and subnephrotic range proteinuria [5.7 (4.12-6.9) pg/mg] were higher (p < 0.05) than in positive [3.7 (2.5-4.82) pg/mg] and negative [3.78 (2.89-4.84) pg/mg] controls. HSP70 expression index in tubular cells positively correlated with urinary HSP70 (Rs = 0.948, р < 0.05) and proteinuria (Rs = 0.362, p < 0.05). The number of TregFoxp3+ cells in the kidney interstitium and interleukin-10 excretion were lower in patients with NS. Anti-HSP70 antibody serum levels in patients with NS [21.1 (17.47-29.72) pg/ml] and subnephrotic range proteinuria [24.9 (18.86-30.92) pg/ml] were significantly higher than in positive [17.8 (12.95-23.03) pg/ml] and negative [18.9 (13.5-23.9) pg/ml] controls. In patients with CGN, increasing proteinuria was associated with higher HSP70 renal tissue and urinary levels. However, activation of HSP70 in patients with nephrotic syndrome did not lead to an increase in tissue levels of TregFoxp3+ cells or to the release of IL-10.
Project description:The family of RAF kinases transduces extracellular information to the nucleus, and their activation is crucial for cellular regulation on many levels, ranging from embryonic development to carcinogenesis. B-RAF and C-RAF modulate neurogenesis and neuritogenesis during chicken inner ear development. C-RAF deficiency in humans is associated with deafness in the rare genetic insulin-like growth factor 1 (IGF-1), Noonan and Leopard syndromes. In this study, we show that RAF kinases are expressed in the developing inner ear and in adult mouse cochlea. A homozygous C-Raf deletion in mice caused profound deafness with no evident cellular aberrations except for a remarkable reduction of the K(+) channel Kir4.1 expression, a trait that suffices as a cause of deafness. To explore the role of C-Raf in cellular protection and repair, heterozygous C-Raf (+/-) mice were exposed to noise. A reduced C-RAF level negatively affected hearing preservation in response to noise through mechanisms involving the activation of JNK and an exacerbated apoptotic response. Taken together, these results strongly support a role for C-RAF in hearing protection.