[Shared functional modules for nasopharyngeal and oral squamous cell carcinoma identified by network analysis of transcriptomes].

Although nasopharyngeal carcinoma (NPC) and oral squamous cell carcinoma (OSCC) are highly correlated clinical diseases, the underling molecular mechanisms to link the two diseases remain largely unknown. The aim of this study is to identify the shared functional modules for NPC and OSCC by using large-scale transcriptomic data. Gene expression profile datasets of NPC and OSCC were obtained from the GEO database. A total of 1279 differentially expressed genes (DEGs) of NPC and 1293 DEGs of OSCC were identified by fold change and empirical Bayes method, and 278 DEGs were common to these two diseases. These overlapped genes were translated into a primary network consisting of 1290 nodes (genes) and 1766 edges. The primary network was then decomposed into 15 compacted modules (subnets) with high modularity by Newman's algorithm. Topological analysis of these modules identified a total of 58 hub genes, most of which (e.g., PCNA, CDK1, STAT1, CCL5, and MMP1) have been proved to be associated with NPC and/or OSCC, while the rest (e.g., MELK, NME1, RACGAP1, INHBA, and NID1) might be novel risk genes for the two diseases. Further bioinformatics analysis of KEGG databases revealed that these modules are involved in multiple pathogenic biological pathways for either NPC or OSCC (e.g., p53 signaling pathway, ECM-receptor interaction, focal adhesion, and cell cycle). This study demonstrates that NPC and OSCC have similar molecular bases, and the identified pleiotropic modules may shape the complicated molecular interplays underlying the two clinically correlated diseases.

[Identification of gene functional modules shared by cancers based on biclustering].

Pleiotropy is a common phenomenon in the genetics of cancers, which is rarely systematically evaluated. A novel idea for identifying shared gene functional modules using biclustering was proposed in this paper to explore the common molecular mechanisms among cancers and the relationships between different types of cancers. Gene expression datasets for 20 cancers were obtained. And genes differentially expressing in at least two types of cancers were selected using both moderated t-statistic and fold change to construct a 10417 × 20 matrix (gene-cancer matrix). 22 gene clusters shared by cancers were found by using the biclustering method. Further, Gene Ontology (GO)-based enrichment analysis identified 17 gene functional modules (Bonferroni corrected P < 0.05). The involved biological processes primarily included regulation of chromatids separation during mitosis, cell differentiation, immune and inflammatory response, and collagen fibril organization. These modules undertook molecular functions of ATP binding and microtubule motor activity, MHC class II receptor activity, endopeptidase inhibitor activity and so on. And their activity sites were mostly located in cytoskeleton, chromosome, MHC protein complex, intermediate filament, fibrillar collagen and so on. The network constructed based on these modules indicates that gastric cancer, ovarian adenocarcinoma, cervical cancer and mesothelioma were highly relevant to each other. However, the molecular mechanisms of two hematologic malignancies (acute myeloid leukemia and multiple myeloma) seem very different from other cancers. It can be seen that gene functional modules shared by cancers are associated with many biological mechanisms, and similarities among cancers are probably attributed to cellular origin and shared carcinogenic mechanisms. The proposed method for analysis of pleiotropy in this paper will help understand the common molecular mechanisms for complex human diseases.

[Advances in development of gene-gene interaction analysis methods based on SNP data: a review].

The SNP-based association analysis has become one of the most important approaches to interpret the underlying molecular mechanisms for human complex diseases. Nevertheless, the widely-used singe-locus analysis is only capable of capturing a small portion of susceptible SNPs with prominent marginal effects, leaving the important genetic component, epistasis or joint effects, to be undetectable. Identifying the complex interplays among multiple genes in the genome-wide context is an essential task for systematically unraveling the molecular mechanisms for complex diseases. Many approaches have been used to detect genome-wide gene-gene interactions and provided new insights into the genetic basis of complex diseases. This paper reviewed recent advances of the methods for detecting gene-gene interaction, categorized into three types, model-based and model-free statistical methods, and data mining methods, based on their characteristics in theory and numerical algorithm. In particular, the basic principle, numerical implementation and cautions for application for each method were elucidated. In addition, this paper briefly discussed the limitations and challenges associated with detecting genome-wide epistasis, in order to provide some methodological consultancies for scientists in the related fields.

Efficacy of combined treatment with albendazole and baicalein against eosinophilic meningitis induced by Angiostrongylus cantonensis in mice.

Angiostrongylus cantonensis infection causes eosinophilic meningitis in humans. Baicalein is a flavonoid originally isolated from the roots of Scutellaria baicalensis Georgi. In this study we evaluated the efficacy of the combination of albendazole and baicalein for treating eosinophilic meningitis in BALB/c mice. Therapeutic efficacy included the survival time, body weight, neurological function, leucocyte and eosinophil counts, eotaxin concentration, matrix metalloproteinase-9 (MMP-9) activity, larval recovery and histopathological examination. The results showed that the combination of albendazole and baicalein was more effective than either drug administered singly. Combination therapy increased the survival time, decreased body weight loss, neurological dysfunction, leucocyte response, eotaxin concentration and MMP-9 activity. Our results suggest that the combination of albendazole and baicalein may exhibit synergistic beneficial effects in the treatment of eosinophilic meningitis induced by A. cantonensis.

Screening mutations of OTOF gene in Chinese patients with auditory neuropathy, including a familial case of temperature-sensitive auditory neuropathy.

BACKGROUND: Mutations in OTOF gene, encoding otoferlin, cause DFNB9 deafness and non-syndromic auditory neuropathy (AN). The aim of this study is to identify OTOF mutations in Chinese patients with non-syndromic auditory neuropathy. METHODS: 73 unrelated Chinese Han patients with AN, including one case of temperature sensitive non-syndromic auditory neuropathy (TS-NSRAN) and 92 ethnicity-matched controls with normal hearing were screened. Forty-five pairs of PCR primers were designed to amplify all of the exons and their flanking regions of the OTOF gene. The PCR products were sequenced and analyzed for mutation identification. RESULTS: Five novel possibly pathogenic variants (c.1740delC, c.2975_2978delAG, c.1194T>A, c.1780G>A, c.4819C > T) were identified in the group of 73 AN patients, in which two novel mutant alleles (c.2975_2978delAG + c.4819C > T) were identified in one Chinese TS-NSRAN case. Besides, 10 non-pathogenic variants of the OTOF gene were found in AN patients and controls. CONCLUSIONS: Screening revealed that mutations in the OTOF gene account for AN in 4 of 73(5.5%) sporadic AN patients, which shows a lower genetic load of that gene in contrast to the previous studies based on other populations. Notably, we found two novel mutant alleles related to temperature sensitive non-syndromic auditory neuropathy. This mutation screening study further confirms that the OTOF gene contributes to ANs and to TS-NSRAN.

[Advances in genetics of restless legs syndrome].

Recent advances in genetic studies on restless legs syndrome (RLS) have led to a series of important discoveries that greatly expand our knowledge on the molecular basis of this disease. RLS is a common and complex disease. Several genetic epidemiological studies and twin studies have characterized the genetic components of RLS and suggest that it is a highly heritable trait with heritability estimates of about 50%. The five chromosomal positions (12q13-23, 14q13-21, 9p24-22, 2q33, and 20p13) have been determined either by model-based linkage analysis or by model-free linkage analysis, which have provided the linkage maps for positional cloning of the underlying genes or susceptibility genes for this disorder. Most recent genome-wide association studies based on high-throughput SNP genotyping platforms have also defined three significantly associated RLS regions (6p21.2, 2p 14, and 15q23). By integrating with our recent genetic studies for this neurological disorder, we reviewed the most important findings achieved in genetic studies of RLS.

[Genetic relationships between Tuva population and the neighboring populations in the Altai Region of Xinjiang Uygur Autonomous Region].

In the Hanasi scenic spot of the Altai Region, Xinjiang Uygur Autonomous Region, China, there is a special population known as Xinjiang Tuvinians for short. These Tuvinians were classified as Mongolians in the early 1950s by the National Ethnic Affairs Commission of China, but they claimed that they have an independent origin. To resolve this dispute and their genetic relationships with the people in the neighboring regions, we randomly selected 150 male Tuvinians in the Altai Region. Fourteen Y chromosomal markers were genotyped and eleven haplogroups were constructed. The frequencies of the haplogroups K-M9 and Q-M242 were higher in Xinjiang Tuvinians or Tuvinians in the Tuva Republic than those in the other populations (e.g., Mongolians and Kazakh). Principal component analysis , multi-dimensional scaling analysis and further phylogenetic tree analysis revealed that the Xinjiang Tuvinians were far separated from Mongolians and Kazakh. Based on these results, we proposed that Xinjiang Tuvinians are genetically distinct from Mongolians and Kazakh.

Rabies trend in China (1990-2007) and post-exposure prophylaxis in the Guangdong province.

BACKGROUND: Rabies is a major public-health problem in developing countries such as China. Although the recent re-emergence of human rabies in China was noted in several epidemiological studies, little attention was paid to the reasons behind this phenomenon paralleling the findings of the previous reports. The purpose of this study is thus first to characterize the current trends of human rabies in China from 1990 to 2007, and then to define better recommendations for improving the post-exposure prophylaxis (PEP) schedules delivered to rabies patients. METHODS: The most updated epidemiological data for 22527 human rabies cases from January 1990 to July 2007, retrieved from the surveillance database of reportable diseases managed by the Ministry of Health of China, were analysed. To investigate the efficiency for the post-exposure treatment of rabies, the details of 244 rabies patients, including their anti-rabies treatment of injuries or related incidents, were ascertained in Guangdong provincial jurisdiction. The risk factors to which the patients were predisposed or the regimens given to 80 patients who received any type of PEP were analysed to identify the reasons for the PEP failures. RESULTS: The results from analysis of the large number of human rabies cases showed that rabies in China was largely under control during the period 1990-1996. However, there has been a large jump in the number of reported rabies cases since 2001 up to a new peak (with an incidence rate of 0.20 per 100000 people) that was reached in 2004, and where the level has remained until present. Then, we analysed the PEP in 244 rabies cases collected in the Guangdong province in 2003 and 2004, and found that 67.2% of the patients did not seek medical services or did not receive any PEP. Further analysis of PEP for the 80 rabies patients who received any type of PEP indicated that almost all of the patients did not receive proper or timely treatment on the wounds or post-exposure vaccination or rabies immunoglobulins. CONCLUSION: While the issue of under-reporting of rabies in previous years may well be a factor in the apparent upwards trend of human rabies in recent years, the analysis of PEP in the Guangdong province provides evidence that suggests that the failure to receive PEP was a major factor in the number of human cases in China. Thus, the data underline the need for greatly improved availability and timely application of high-quality anti-rabies biologicals, both vaccines and immunoglobulins, in the treatment of human bite victims. Controlling dog rabies through pet vaccination schemes may also play a huge role in reducing the rate of human exposure. Education of the public, health care staff and veterinarians will also help to change the current situation.

GJB2, SLC26A4 and mitochondrial DNA A1555G mutations in prelingual deafness in Northern Chinese subjects.

CONCLUSION: This genetic epidemiological study demonstrated that 26.65% of the prelingual deafness in Northern Chinese patients can be detected at younger ages by genetic testing of three common hearing loss genes (GJB2, SLC26A4 and mtDNA A1555G), and thus, early intervention measures could be undertaken to help them in language acquisition. OBJECTIVES: The GJB2, SLC26A4 and mtDNA A1555G mutations are the prevalent causes of prelingual deafness worldwide. Numerous studies have revealed that the forms and frequencies of the mutations in the three genes are largely dependent on the ethnic or geographic origins. Hence, this study aimed to characterize the mutation profiles of the three genes in prelingual deafness in Northern Chinese patients. SUBECTS AND METHODS: An investigation of 514 patients with prelingual deafness and 117 controls with normal hearing was conducted. Bidirectional sequencing (or enzyme digestion) was applied to identify sequence variations. RESULTS: This study revealed that 26.65% patients had two mutated alleles (homozygote or compound heterozygote) of GJB2 (9.14%) or SLC26A4 (8.95%) and/or an mtDNA A1555G (8.56%) mutation. In detail, 19.26% patients carried GJB2 mutations including 10.12% single mutant carriers. 235delC was the most common type, making up 69.18% of all mutants for GJB2. The mutant carrier rate for SLC26A4 was 15.2%, including 6.23% single mutant carriers. The two most common types (IVS7-2A > G and H723R) accounted for 51.61% and 33.06% mutations, respectively. Forty-five patients had mtDNA A1555G, giving a frequency of 8.75%. In the control group with normal hearing, 2.56%, 1.71% and 0% of the subjects carried a single mutant for GJB2, SLC26A4 and mtDNA A1555G, respectively.

A novel mutation of POU3F4 causes congenital profound sensorineural hearing loss in a large Chinese family.

OBJECTIVES/HYPOTHESIS: It is known that approximately 5% of congenital profound hearing impaired cases are inherited in X-linked inheritance. This study aimed at identifying its underlying molecular determinant(s) using a large, five-generation Chinese family with multiple familial cases. STUDY DESIGN: Model-based linkage analysis and positional cloning. METHODS: Model-based genetic linkage analyses were performed with the use of microsatellite polymorphisms to determine disease locus. Mutation screening was performed within the family and unrelated population-based controls to establish molecular evidence as to what caused the specific X-linked inheritance pattern in the family. RESULTS: Clinical investigations of the pedigree demonstrated the extremely high penetrance in the male members but no penetrance in the female members. Linkage analyses mapped the disease to the chromosomal region Xq13.I-Xq23 (maximum X-linkage logarithm of odds score = 3.27). Mutation screening of the candidate genes in the linkage region by direct sequencing revealed a de novo missense substitution (925T>C) in the well-known deaf gene. POU3F4. Direct sequencing on 240 unrelated controls did not detect any mutation. CONCLUSIONS: Multiple analysis approaches demonstrated that these disorders in the family were caused by a founder mutation in the POU3F4 gene. Our findings provided confirmatory molecular evidence to support that development of congenital profound sensorineural hearing loss in the Chinese population results from a novel mutation in the same gene.

Decision forest analysis of large-scale sib-pair identical-by-decent profiles for locating the underlying disease genes for alcoholism in human.

OBJECTIVE: To extract the relevant SNPs for alcoholism using sib-pair IBD profiles of pedigrees. METHODS: We used the ensemble decision approach, a supervised learning approach based on decision forests, to locate alcoholism relevant SNPs using genome-wide SNP data. RESULTS: Application to a publicly available large dataset of 100 simulated replicates for three American populations (http://www.gaworkshop.org/) demonstrates that the proposed approach has successfully located all of the simulated true loci. CONCLUSION: The numerical results establish the proposed decision forest analysis to be a powerful and practical alternative for large-scale family-based association study.

Novel strategies to identify relevant molecular signatures for complex human diseases based on data of identical-by-decent profiles and genomic context.

OBJECTIVE: To develop novel strategies to identify relevant molecular signatures for complex human diseases based on data of identical-by-decent profiles and genomic context. METHODS: In the proposed strategies, we define four relevancy criteria for mapping SNP-phenotype relationships-point-wise IBD mean difference, averaged IBD difference for window, Z curve and averaged slope for window. RESULTS: Application of these criteria and permutation test to 100 simulated replicates for two hypothetical American populations to extract the relevant SNPs for alcoholism based on sib-pair IBD profiles of pedigrees demonstrates that the proposed strategies have successfully identified most of the simulated true loci. CONCLUSION: The data mining practice implies that IBD statistic and genomic context could be used as the informatics for locating the underlying genes for complex human diseases. Compared with the classical Haseman-Elston sib-pair regression method, the proposed strategies are more efficient for large-scale genomic mining.

[Analysis of diffuse large B-cell lymphoma heterogeneity based on coupled two-way clustering].

Microarray technology has proposed a powerful tool in dealing with the heterogeneity of disease. Currently, many methods in the field are based on traditional hierarchical clustering to discover subtypes of disease using a large number of genes on microarray.However, they did not considered that large unrelated noise (genes)may mask significant partitions and correlations of disease samples. To avoid the shortcoming, this paper presented a heterogeneous analysis based on coupled two-way clustering (HCTWC) to search interesting gene signature and find the natural partitions of disease samples. The method was applied to diffuse large B-cell lymphoma (DLBCL) microarray dataset. By identifying significant gene signature, we were able to discover the two new subtypes of DLBCL with survival rate 55% and 25% respectively. The results showed that HCTWC had the potential to be a powerful tool for solving the heterogeneity of disease on gene expression profile.

Identification of Risk Pathways and Functional Modules for Coronary Artery Disease Based on Genome-wide SNP Data.

Coronary artery disease (CAD) is a complex human disease, involving multiple genes and their nonlinear interactions, which often act in a modular fashion. Genome-wide single nucleotide polymorphism (SNP) profiling provides an effective technique to unravel these underlying genetic interplays or their functional involvements for CAD. This study aimed to identify the susceptible pathways and modules for CAD based on SNP omics. First, the Wellcome Trust Case Control Consortium (WTCCC) SNP datasets of CAD and control samples were used to assess the joint effect of multiple genetic variants at the pathway level, using logistic kernel machine regression model. Then, an expanded genetic network was constructed by integrating statistical gene-gene interactions involved in these susceptible pathways with their protein-protein interaction (PPI) knowledge. Finally, risk functional modules were identified by decomposition of the network. Of 276 KEGG pathways analyzed, 6 pathways were found to have a significant effect on CAD. Other than glycerolipid metabolism, glycosaminoglycan biosynthesis, and cardiac muscle contraction pathways, three pathways related to other diseases were also revealed, including Alzheimer's disease, non-alcoholic fatty liver disease, and Huntington's disease. A genetic epistatic network of 95 genes was further constructed using the abovementioned integrative approach. Of 10 functional modules derived from the network, 6 have been annotated to phospholipase C activity and cell adhesion molecule binding, which also have known functional involvement in Alzheimer's disease. These findings indicate an overlap of the underlying molecular mechanisms between CAD and Alzheimer's disease, thus providing new insights into the molecular basis for CAD and its molecular relationships with other diseases.

Psychometric properties of the coronary heart disease scale of the quality-of-life instruments for chronic diseases (QLICD-CHD): an application to Cantonese patients.

The purpose of this study was to validate the applicability of our proposed disease-specific questionnaire to Cantonese coronary heart disease (CHD) patients. During the investigation from August 2010 to March 2012, 1000 Cantonese inpatients were recruited. The reliability of the scale was judged by the internal consistency, and the content and construct validity were assessed by using Pearson correlation and confirmatory factor analysis, respectively. Results showed that the Cronbach's α coefficient for the whole scale and most domains/facets were larger than .70 (.59 to .93). Most items had moderate to strong Pearson correlations with their respective facets (r > 0.50). Confirmatory factor analysis showed that the indices for goodness of fit were nearly acceptable. Overall, the QLICD-CHD scale has adequate psychometric properties when applied to Cantonese CHD patients.

Pathway-based analysis tools for complex diseases: a review.

Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehensive understanding of the molecular mechanisms underlying complex diseases. Extensive studies utilizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods-the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available pathway-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are discussed. This review will provide a useful guide to dissect complex diseases.

A meta-analysis of the association between TNF-α -308G>A polymorphism and type 2 diabetes mellitus in Han Chinese population.

OBJECTIVE: A meta-analysis was applied to evaluate the associations between tumor necrosis factor-α (TNF-α) -308G>A (rs1800629) polymorphism and type 2 diabetes mellitus (T2DM). METHODS: Hardy-Weinberg equilibrium (HWE) was employed to test genetic equilibrium among the genotypes of the selected literature. Power analysis was performed with the Power and Sample Size Calculation (PS) program. A fixed or random effect model was used on the basis of heterogeneity. Publication bias was quantified and examined with the Begg's funnel plot test and Egger's linear regression test. The meta-analysis was performed with Review Manager 5.1 and Stata 11.0. RESULTS: There were 10 studies including 1425 T2DM patients and 1116 healthy control subjects involved in this meta-analysis. No significant publication bias was found in the studies. The pooled ORs (95% CIs) for TNF-α -308G>A of A vs. G allele and GA+AA vs. GG genotype were 1.63 (1.17-2.25) and 1.47 (1.17-1.85), respectively. CONCLUSION: This meta-analysis result suggested that TNF-α -308G>A polymorphism was strongly associated with T2DM risk, and A allele at this locus might be a susceptibility allele for the development of T2DM in Han Chinese population.

Laryngeal aerodynamic analysis in assisting with the diagnosis of muscle tension dysphonia.

OBJECTIVE/HYPOTHESIS: To estimate the aerodynamic multiparameters for patients with muscular tension dysphonia (MTD) and evaluate voice aerodynamic analysis for assisting the diagnosis of this disorder. STUDY DESIGN: A prospective study. METHODS: Voice aerodynamic parameters, including subglottal pressure (SGP) level, glottal resistance (GR), mean airflow rate (MFR), and maximum phonation time (MPT), for 26 MTD patients and 27 normal adults were analyzed using receiver operating characteristics (ROC) analysis and multivariate logistic regression. RESULTS: For male samples, MTD patients had higher SGP (P=0.001), higher GR (P=0.012), lower MFR (P=0.042), and shorter MPT (P=0.027), whereas for female samples, the difference between cases and controls was statistically significant only in SGP (P<0.001) and MPT (P<0.001). ROC analysis showed that the threshold of 8.175 cm H(2)O for SGP achieved a good classification for MTD, with an adequate sensitivity (76.9%) and the perfect specificity (100%). Finally, multivariate logistic regression established a credible model (with SGP and MPT as the predictors) for classifying MTD, with a 92.5% percentage correct. CONCLUSIONS: This analysis indicates that aerodynamics evaluation could help the diagnosis of MTD patients, jointly with medical history scrutiny, physical examination, fibrolaryngoscopy, and/or videoendostroboscopy.

Newborn hearing concurrent gene screening can improve care for hearing loss: a study on 14,913 Chinese newborns.

OBJECTIVE: Newborn hearing screening has been widely adopted and made an achievement to some degree. Current screening protocols rely solely on detecting existing auditory disorders at the time of screening and are unable to identify individuals susceptible to auditory disorders in later life. Even if the hearing loss newborn is referred, most cases could not be diagnosed until 6-12 months old with no etiology being elucidated. This study reports the first effort to combine traditional hearing screening with genetic screening to improve the efficacy of newborn hearing screening. METHODS: This study was undertaken in 12 regional hospitals located in 11 provinces of China. 14,913 newborn babies received hearing concurrent genetic screening. The hearing screening was performed with OAE or AABR. Blood sample was collected with a universal newborn genetic screening card. And three common gene, mtDNA 12S rRNA, GJB2 and SLC26A4 were screened with standard protocol. RESULTS: Among all the 14,913 newborns, 86.1% (12,837/14,913) individuals passed the first-step hearing screening, 7.8% (1168/14,913) babies passed only one side, and the other 6.1% (908/14,913) were bilaterally referred. Gene screening found 306 individuals had one or two mutant alleles, the carrier rate is 2.05% (306/14,913) among the entire newborn population. The risk for hearing loss was 100% (7/7) for those newborns carrying causative GJB2 or SLC26A4 mutations (homozygotes or compound heterozygotes), 14.4% (23/160) for GJB2 heterozygote carriers, 12.3% (15/122) for SLC26A2 heterozygous carriers, and the total prevalence of referral hearing screening was approximately 14.7% (45/306). However, 85.3% (261/306) newborns passed hearing screening among these carriers including 18 newborns with 12S rRNA mt.1555A>G pathogenic mutation, who would suffer from sudden hearing loss once applying aminoglycoside drugs. CONCLUSION: The cohort studies provided the essential population parameters for developing effective programs for hearing care of newborns in China. Hearing concurrent gene screening in newborns may confirm the abnormal results from hearing screening tests, help to find the etiologic of the hearing loss, and better recognize infants at risk for late-onset hearing loss occurring prior to speech and language development. In conclusion, a survey on 14,913 Chinese newborns proved that concurrent genetic screening could improve newborn hearing screening for hearing defects.

Association between polymorphisms in SOD1 and noise-induced hearing loss in Chinese workers.

CONCLUSION: SOD1 is an important gene related to noise-induced hearing loss (NIHL), and its effect is dependent on noise exposure levels. OBJECTIVES: To test whether the polymorphisms in the CuZn-superoxide dismutase gene (SOD1) are associated with susceptibility to NIHL in the Chinese population. METHODS: Audiometric data from 2400 Chinese Han people exposed to occupational noise were analyzed. DNA samples were collected from the 10% most susceptible and the 10% most resistant individuals. Four SNPs in the introns of SOD1 were genotyped and their effects and interactions with noise exposure were analyzed. RESULTS: Genotype AA of rs2070424 conferred protection against NIHL (adjusted OR = 0.45, p = 0.005), while GG of rs10432782 was a risk genotype (adjusted OR = 1.88, p = 0.026). One protective haplotype TATG (OR = 0.56, p = 0.003) and two risk haplotypes, CATG and TGGA (OR = 1.58, 28.75 and p = 0.017, <0.001, respectively) were identified. Significant interactions between SOD1 SNPs and noise levels were found. Further analysis of effects of SOD1 SNPs found that those carrying GG genotype of rs10432782 had significantly higher SOD1 activity (p = 0.022), but a significantly lower level of malondialdehyde in plasma, compared with TT carriers (p = 0.007).