Dataset Information

Polymorphisms of heat shock protein 70 genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility of noise-induced hearing loss in a Chinese population: A case-control study.

ABSTRACT: 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.

SUBMITTER: Li Y

PROVIDER: S-EPMC5300111 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Polymorphisms of heat shock protein 70 genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility of noise-induced hearing loss in a Chinese population: A case-control study.

Li Yanhong Y Yu Shanfa S Gu Guizhen G Chen Guoshun G Zheng Yuxin Y Jiao Jie J Zhou Wenhui W Wu Hui H Zhang Zengrui Z Zhang Huanling H He Lihua L Yang Qiuyue Q Xu Xiangrong X

PloS one 20170209 2

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 wit ...[more]

PMID: 28182740

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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: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.

Dataset Information

Polymorphisms of heat shock protein 70 genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility of noise-induced hearing loss in a Chinese population: A case-control study.

Publications

Polymorphisms of heat shock protein 70 genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility of noise-induced hearing loss in a Chinese population: A case-control study.

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