Huanxi Shen

REV3L 3′UTR 460 T>C polymorphism in microRNA target sites contributes to lung cancer susceptibility

REV3Lp, the catalytic subunit of DNA polymerase zeta, is the major participant in translesion DNA synthesis. Recent evidence suggests that REV3L has an important role in the maintenance of genome stability despite its mutagenic characteristics. Such a function makes it a cancer susceptibility candidate gene. To investigate association between REV3L polymorphisms and lung cancer risk in a Chinese population, we first genotyped 15 common polymorphisms of the REV3L gene and found that three single nucleotide polymorphisms (rs465646, rs459809 and rs1002481) were significantly associated with lung cancer risk. One of the strongest associations observed was for the 3′-terminal untranslated region (3′UTR) 460 T>C polymorphism (rs465646) (adjusted odds ratio (OR)=0.69 for TC/CC; P=0.007, compared with TT). Similar results were obtained in a subsequent replication study (adjusted OR=0.72; P=0.016). Combined data from the two studies of 1072 lung cancer patients and 1064 cancer-free controls generated an even stronger association (adjusted OR=0.71; P=3.04 × 10−4). This 3′UTR 460 T>C variant was predicted to modulate the binding of several micro RNAs. Surface plasmon resonance analysis and luciferase assays showed that the T allele demonstrated a stronger binding affinity for miR-25 and miR-32, resulting in significantly weaker reporter expression levels. Additional experiments revealed that miR-25/32 could downregulate endogenous REV3L. Furthermore, the tumor-suppressing role of REV3L was confirmed by the foci formation assay. These results support our hypothesis that the REV3L rs465646 variant modifies lung cancer susceptibility in Chinese Han population by affecting miRNA-mediated gene regulation.

A functional Ser326Cys polymorphism in hOGG1 is associated with noise-induced hearing loss in a Chinese population.

DNA damage to cochlear hair cells caused by 8-oxoguanine (8-oxoG) is essential for the development of noise-induced hearing loss (NIHL). Human 8-oxoG DNA glycosylase1 (hOGG1) is a key enzyme in the base excision repair (BER) pathway that eliminates 8-oxoG. Many epidemiological and functional studies have suggested that the hOGG1 Ser326Cys polymorphism (rs1052133) is associated with many diseases. The purpose of this investigation was to investigate whether the hOGG1 Ser326Cys polymorphism in the human BER pathway is associated with genetic susceptibility to NIHL in a Chinese population. This polymorphism was genotyped among 612 workers with NIHL and 615 workers with normal hearing. We found that individuals with the hOGG1 Cys/Cys genotype had a statistically significantly increased risk of NIHL compared with those who carried the hOGG1 Ser/Ser genotype (adjusted OR = 1.59, 95% CI = 1.13–2.25) and this increased risk was more pronounced among the workers in the 15- to 25- and >25-year noise exposure time, 85–92 dB(A) noise exposure level, ever smoking, and ever drinking groups, similar effects were also observed in a recessive model. In summary, our data suggested that the hOGG1 Cys/Cys genotype may be a genetic susceptibility marker for NIHL in the Chinese Han population.

Genetic Variations in the Promoter of the APE1 Gene Are Associated with DMF-Induced Abnormal Liver Function: A Case-Control Study in a Chinese Population.

Acute or long-term exposure to N,N-dimethylformamide (DMF) can induce abnormal liver function. It is well known that DMF is mainly metabolized in the liver and thereby produces reactive oxygen species (ROS). The base excision repair (BER) pathway is regarded as a very important pathway involved in repairing ROS-induced DNA damage. Several studies have explored the associations between GSTM1, GSTT1, CYP2E1 polymorphisms and DMF-induced abnormal liver function; however, little is known about how common hOGG1, XRCC1 and APE1 polymorphisms and DMF induce abnormal liver function. The purpose of this study was to investigate whether the polymorphisms in the hOGG1 (rs159153 and rs2072668), XRCC1 (rs25487, rs25489, and rs1799782), APE1 (rs1130409 and 1760944) genes in the human BER pathway were associated with the susceptibility to DMF-induced abnormal liver function in a Chinese population. These polymorphisms were genotyped in 123 workers with DMF-induced abnormal liver function and 123 workers with normal liver function. We found that workers with the APE1 rs1760944 TG/GG genotypes had a reduced risk of abnormal liver function, which was more pronounced in the subgroups that were exposed to DMF for <10 years, exposed to ≥10 mg/m3 DMF, never smoked and never drank. In summary, our study supported the hypothesis that the APE1 rs1760944 T > G polymorphism may be associated with DMF-induced abnormal liver function in the Chinese Han population.

Association between Paraoxonase 2 Gene Polymorphisms and Noise-induced Hearing Loss in the Chinese Population

Association between Paraoxonase 2 Gene Polymorphisms and Noise‐induced Hearing Loss in the Chinese Population: Xiu‐Ting LI, et al. Department of Occupational Medicine and Environmental Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, China—

Association of genetic variations in FOXO3 gene with susceptibility to noise induced hearing loss in a Chinese population

Noise induced hearing loss (NIHL), a multifactorial disease involving both genetic and environmental factors, is one of the most important occupational health hazards. Nonetheless, the influence of FOXO3 variants on NIHL risk have not been illuminated. This research was conducted to explore the effects of FOXO3 polymorphisms on individual susceptibility to NIHL. A total of 2689 industrial workers from one textile factory of east China were recruited to participate in the current research. Venous blood was collected, questionnaire and pure-tone audiometry (PTA) was conducted by specialist physicians. Then, we performed genotyping of three selected SNPs (rs2802292, rs10457180, and rs12206094) in FOXO3 gene in 566 NIHL patients and 566 controls. Subsequently, the main effects of genotype and its interactions were evaluated. Our results revealed that individuals with the G allele of rs2802292, G allele of rs10457180, T allele of rs12206094 (OR = 1.43, 1.43, and 1.31 respectively) and the haplotype GAC and others (TGT/GGT/GGC/GAT) (rs2802292-rs10457180-rs12206094) (OR = 1.49 and 2.09 respectively) are associated with an increased risk of NIHL in a Chinese population. Stratified analysis showed that an increased NIHL risk was found in the subjects who exposed to noise >16 years with rs2802292 GG/GT and rs10457180 AG/GG genotype with an OR of 1.62 and 1.66 respectively. Multifactor dimensionality reduction analysis indicated that rs10457180, rs2802292, and rs12206094 have interactions and are related to increased NIHL risk (OR = 1.53). The genetic polymorphism rs2802292, rs10457180, and rs12206094 within FOXO3 gene are associated with an increased risk of NIHL in a Chinese population and have potential to be biomarkers for noise exposed workers.

DNMT1 and DNMT3A haplotypes associated with noise-induced hearing loss in Chinese workers

This study was conducted to explore the effects of DNMT1 and DNMT3A polymorphisms on susceptibility to noise-induced hearing loss (NIHL) in Chinese workers. A total of 2689 industrial workers from a single textile factory were recruited. Venous blood was collected, as were questionnaire and pure-tone audiometry (PTA) data by specialist physicians. Four selected SNPs (rs7578575, rs749131, rs1550117, and rs2228611) in DNMT1 and DNMT3A were genotyped in 527 NIHL patients and 527 controls. Then, main effects of the genotypes and their interactions were evaluated. Results revealed that the GG genotype at rs749131 and the AG/GG genotypes at rs1550117 and rs2228611 [odds ratio (OR) = 1.87, 2.57, and 1.98 respectively], as well as the haplotypes AGGG and TGGA (rs7578578-rs749131-rs1550117-rs2228611) (OR = 1.35 and 1.56, respectively) were associated with an increased risk of NIHL in the Chinese population. Multifactor dimensionality reduction analysis indicated that rs7578575, rs749131, and rs2228611 interact and are related to increased NIHL risk (OR = 1.63). The genetic polymorphisms rs749131 G, rs1550117 G, and rs2228611 G within the DNMT1 and DNMT3A genes are associated with an increased risk of NIHL in the Chinese population and have the potential to act as biomarkers for noise-exposed workers.

Association between blood lead level and blood pressure: An occupational population-based study in Jiangsu province, China

Studies about the association between lead exposure and the elevation of blood pressure and risk of hypertension are varied, while available data on blood lead levels (BLL) in workers with lead-exposure are scarce. This research aimed to evaluate associations between BLL and blood pressure in an occupational population-based study in Jiangsu province, China. We enrolled 21,688 workers in this study. Information on socioeconomic and occupational background was obtained with face-to-face interviews. BLL, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured, and hypertension status was confirmed. We found that workers in mini-factories had the highest average BLL (20.3 μg/dL; 95% CI, 19.0–21.6 μg/dL) for overall participants. The employees in private factories had higher BLL (9.6 μg/dL; 95% CI, 9.5–9.8 μg/dL). However, BLL was much lower (4.0 μg/dL; 95%CI, 3.7–4.2 μg/dL) in state-owned factories. Participants working in the electrical machinery and equipment manufacturing industry had higher BLL (9.1 μg/dL; 95% CI, 9.0–9.3μg/dL). Compared to those workers with ≤ 4.6 μg/dL BLL, workers with > 17.5 μg/dL BLL presented 1.34 mmHg and 0.70 mmHg average difference in SBP and DBP, respectively. The adjusted OR for hypertension was 1.11 (95%CI, 1.08–1.15) compared to the workers with > 17.5 μg/dL BLL and to those with ≤ 4.6 μg/dL BLL. In summary, we found that BLL was positively associated with SBP and DBP and with the morbidity of hypertension in occupational populations with a high concentration of lead exposure. It is important to formulate new standards of blood lead levels to screen for elevated lead exposure. In addition, a series of new systems of risk assessment should be established to further reduce and prevent lead exposure.

Association between plasma membrane Ca 2+ -ATPase gene polymorphisms and noise-induced hearing loss in a Chinese population

Background: Noise-induced hearing loss (NIHL) has become a world-wide high occupational health risk. The current research is aimed at investigating the association of plasma membrane Ca 2+ -ATPase isoform 2 ( PMCA2 ) gene polymorphisms with the susceptibility to NIHL in a Chinese population. Methods: A total of 2,344 workers exposed to occupational noise were examined with hearing tests. According to the results of audiometry, we selected 613 cases with high frequency hearing threshold worse than 25 dB and 615 controls with high frequency hearing threshold better than or equal to 25 dB and the controls were frequency matched with cases in terms of age, gender and noise exposure level and exposure time. The individual genotypes for PMCA2 single nucleotide polymorphisms (SNPs) were determined using a TaqMan MGB probe assay performed on an ABI PRISM ® 7900 HT Fast Real-Time PCR System (Applied Biosystems). Information about these subjects was collected by questionnaires which were conducted through face-to-face interviews by trained interviewers. Results: We found that individuals with the rs3209637 CC genotype had a statistically significantly increased risk of NIHL compared with those who carried the rs3209637 TT genotype (adjusted OR =1.26, 95% CI =1.07–1.48) and this increased risk was more pronounced among the workers in the 15- to 25-year noise exposure time, >92 dB(A) noise exposure level. Similar effects were also observed in a recessive model. Conclusions: Our data suggested that the PMCA2 polymorphisms may be a genetic susceptibility marker for NIHL in the Chinese Han population.

Association of TagSNP in lncRNA HOTAIR with susceptibility to noise-induced hearing loss in a Chinese population

Background: Noise‐induced hearing loss (NIHL) is a multifactorial disease, and dysregulation of oxidative stress is universally acknowledged as one crucial pathogenic factor for this disease. Recently studies have found the LncRNA HOTAIR is involved in the alteration of oxidative stress level, cell proliferation, cell cycle progression, and apoptosis. Considering the effects of lncRNA HOTAIR in cellular oxidative stress, we sought to investigate the influence of lncRNA HOTAIR variants on the risk of NIHL. Methods: To explore the effects of HOTAIR polymorphisms on individual susceptibility to NIHL, We performed genotyping of three tagSNPs (rs874945, rs4759314 and rs7958904) in HOTAIR gene in a Chinese population which consists of 570 NIHL cases and 570 controls. The luciferase assays were further performed to investigate the regulatory function of HOTAIR tagSNPs. Results: Our results revealed individuals with the G allele of HOTAIR tagSNP rs4759314 and the haplotype (rs874945, rs4759314 and rs7958904) are associated with an increased risk of NIHL in a Chinese population. Meanwhile, the rs4759314 G allele could significantly increase the expression of lncRNA HOTAIR. Conclusions: The genetic polymorphism within HOTAIR gene may play a crucial role in the occurrence and development of NIHL. HIGHLIGHTSProposing the possibility of the association between the LncRNA and Noise Induced Hearing Loss.Investigating the function of SNPs in LncRNA HOTAIR in NIHL.Analyzing and identifying the significance of SNPs in a case‐control study in NIHL.

Correlation between CAT polymorphism and susceptibility to DMAc-Induced Abnormal Liver Function: A case-control study of Chinese Population

Abstract Context: Acute or chronic exposure of N,N-dimethylacetamide (DMAc) is responsible for abnormal liver function. It appears that DMAc is mainly metabolized by cytochrome P450 in the liver and thereby produces reactive oxygen species (ROS). The elimination of ROS and the repairing of ROS-induced DNA damage are relevant to the ultimate toxicity of DMAc. Objective: To investigate whether the polymorphisms in the CAT (rs564250, rs769214 and rs7943316), hOGG1 (rs2072668 and rs159153) and XRCC1 (rs25487 and rs1799782) genes are associated with susceptibility to DMAc-induced abnormal liver function in Chinese population. Methods: Samples were obtained from 108 workers with DMAc-induced abnormal liver function and 108 workers with normal liver function. Results: Subjects with the CAT rs769214 GA/GG genotypes had a reducing risk of abnormal liver function, which was more evident in the subgroups exposed to DMAc <10 years, exposed to DMAc <5 mg/m3, never smoked and never drank. Conclusions: CAT rs769214 (-844 G > A) polymorphism may be associated with DMAc-induced abnormal liver function in Chinese population.