| Background:Lead has become one of the most widely used metals in the world in recent years due to its good ductility,flexibility,plasticity,low melting point,easy access and corrosion resistance.According to the statistical report of China Center for Disease Control and Prevention,there were 1224 cases of occupational lead poisoning(blood lead concentration>600?g/L)in China from 2012 to 2016,ranking first in the number of chronic occupational poisoning cases in China.With the acceleration of industrialization process,environmental pollution caused by heavy metals is also increasing.Children's excessive lead intake has become a problem that can not be ignored in the field of public health.Lead enters the body through respiratory tract,digestive tract and other channels,and is transported to various tissues and organs with blood.It is toxic to skeletal system,nervous system,blood system,immune system,digestive system,reproductive endocrine system and urinary system.Most of the lead entering the body is deposited in bone in the form of lead salts or lead-protein complexes,which are released into the blood again with the process of bone remodeling,causing continuous damage to the body.Inorganic lead has been identified as a potential group 2A carcinogen by the International Agency for Research on Cancer(IARC).Different individuals in the same external exposure environment often show different lead exposure,suggesting that there are differences in susceptibility to lead poisoning among people.Long non-coding RNA(lncRNA)is a kind of RNA transcripts without protein coding function.Its length is often more than 200 bp.For a long time,lncRNA has been regarded as a nonfunctional "junk sequence" accumulated during the evolution of the genome.However,with the deepening of research,it has been proved that it has important biological functions,affecting the occurrence and development of diseases.In our previous studies,we found that the expression levels of lncRNA HOTAIR were differentially expressed in workers exposed to different lead doses,so we speculated that lncRNA HOTAIR might be involved in the lead poisoning process.Objective:Based on the hygienic investigation of blood lead load of workers at different jobs in lead-acid battery enterprises in Jiangsu Province,the association between polymorphism of lncRNA HOTAIR gene and susceptibility to lead poisoning was studied,and the clues of whether there were lncRNA molecular markers that could characterize susceptibility to lead poisoning were found.Methods:A cross-sectional study was conducted to investigate the lead exposure level of workers in different jobs in lead-acid battery enterprises in Jiangsu Province.According to the "Sampling Code for Monitoring Hazardous Substances in the Air of Workplace"(GBZ159-2004)and the requirements of "Determination of Lead and Its Compounds in the Air of Workplace"(GBZ/T160.10-2004),the exposure concentration of lead was determined and the time-weighted average concentration of lead in the air of each measuring point was calculated.Occupational health examination was carried out for workers.The blood lead content was determined by WS/T 20-1996 graphite furnace atomic absorption spectrometry.A case-control study was conducted.After matching gender,age and environmental lead exposure levels,10% of the people with the highest bleeding lead concentration were selected as susceptible group(blood lead >400?g/L)and 10% of the people with the lowest bleeding lead concentration were selected as tolerant group(blood lead <400?g/L).Genomic DNA was extracted from susceptible and tolerant groups.In view of the gene sequence encoding lncRNA HOTAIR,tag-SNPs were screened in well-known and authoritative databases such as NCBI SNP database,according to the principle that there are literature reports and minimum allele frequency(MAF)> 0.05 in Chinese population.TaqMan probe and real-time PCR were used to genotype the single nucleotide polymorphism loci of HOTAIR gene.The distribution of each genotype was compared between the two groups.Logistic regression was used to analyze the relationship between HOTAIR gene polymorphism and susceptibility to lead poisoning.Results:(1)Occupational health field survey showed that the surveyed lead-acid batteries enterprises had a high degree of automation in production,complete occupational hazard protection measures,and low exposure value of lead in the air of their workplace.In order to exclude the influence of lead exposure concentration on this study,1130 workers with similar lead exposure were selected as the study subjects.The C-TWA values of lead exposure in their jobs ranged from0.022± 0.003 to 0.027 ± 0.001 mg/m3.(2)Demographic data of physical examination workers show that the age of lead-exposed workers is mainly about 40-50 years old,and 46.2% of them have been exposed to lead for more than three years.This shows that the survey subjects are mainly skilled workers,which is representative.The lead exposure time of susceptible group was 20.31 ± 1.93 months,and that of tolerant group was54.44 ± 4.32 months months.There was significant difference in lead exposure time between the two groups(P < 0.01).It showed that under similar exposure concentration,susceptible group was more likely to cause the increase of blood lead concentration in a shorter time than tolerant group.(3)Laboratory tests of blood lead showed that the average blood lead level of this population was 386.73 ± 177.93?g/L,134 people exceeded the standard,and the rate of exceeding the standard was 11.86%.The mean blood lead in susceptible group was513.52±63.86?g/L,while that in tolerant group was 89.34±15.39?g/L.The difference between the two groups was statistically significant(P < 0.05).(4)The linkage disequilibrium analysis of the association between HOTAIR genotype and susceptibility to lead poisoning showed that there were three SNP loci in the coding gene of lncRNA HOTAIR,namely rs7958904,rs4759314 and rs874945.The allele frequency distribution of rs7958904 locus in susceptible and tolerant populations conformed to Hardy-Weinberg equilibrium law(P > 0.05),and rs7958904 locus was associated with susceptibility to lead poisoning(P < 0.05).The results showed that the G allele of rs7958904 in lead-susceptible group was significantly lower than that in lead-tolerant group(16.81% vs 26.11%,P = 0.016,OR = 0.56,95% CI = 0.35-0.90).Logistic regression analysis showed that workers carrying CG/GG genotype at rs7958904 locus could reduce the risk of lead poisoning,OR was 0.49(P = 0.013,95% CI = 0.28-0.86).(5)There were significant statistical differences in age and smoking between CC and CG/GG genotypes(P < 0.01)by stratified analysis of demographic data on the relationship between different genotypes at rs7958904 locus and risk of lead poisoning.There were significant differences in education,drinking and workshop diet(P < 0.05).The CG/GG genotype of rs7958904 was associated with the risk of lead poisoning among workers aged 35 and under(P < 0.01).Compared with workers with CC genotype,the risk of lead poisoning was reduced(OR = 0.31,95% CI = 0.13-0.74).However,no relationship between rs7958904 locus and lead poisoning was found among workers older than 35 years old(P > 0.05).Conclusions:(1)The polymorphism of HOTAIR gene is related to the susceptibility to lead poisoning.rs7958904 locus is significantly related to the susceptibility to lead poisoning.G allele is a protective factor relative to C allele.CG/GG genotype can reduce the risk of lead poisoning and play a protective role in the occurrence of lead poisoning.(2)HOTAIR gene is a susceptible gene for lead poisoning,which can provide clues and ideas for further searching for molecular markers for pre-job screening of lead workers. |
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