Polymorphism Study Of Promoter Region Of The Tumor Necrosis Factor-α (TNF-α) In Benzene Poisoning

Polymorphism study of promoter region ofthe tumor necrosis factor-α(TNF-α)in Benzene poisoningObjective:To study whether individuals with polymorphisms at the promoter region of thetumor necrosis factor-αgene (TNF-α)(sites at-238 nt and-308 nt,-857 nt and-863nt)are susceptible for chronic Benzene poisoning.Method:The polymorphic sites of the TNF-αgene were PCR amplified from DNAextracted from 46 benzene poisoning patients (BP1),23 benzene induced bonemarrow dysplasia (BP2),132 healthy non-exposed controls(B~-controls),141 healthyexposed individuals(B~+controls),95 MDS patients with no benzene exposure(B~-MDS)and 89 patients with no MDS.The PCR fragments were digested with appropriaterestriction enzymes and then analyzed by gel electrophoresis.Case-control study wasused in this study.The gold satandard for BP1 and BP2 according to the GBZ 2002 ofRepubplic China and bone marrow examination.Occupational exposure to benzenewas confirmed by review of factory industrial hygine monitoring records,real timequantitative industrial hygiene analysis,including personal samples and breathingzone analyses.The questionnaire for this case-control study included histories ofmedications (Chloramphenicol,Sulfonamides,Meprobamate,Phenatoin,Colchicine,Cyclophosphamide,Propylthiouracil,Anti-TB medication,Tolbutamind,Primaquineand Chinese traditional herbs such as Bezoar,Angelica,Arsennic,Thunder cloud vine)at least 5 years prior to the onset of the disease,tumors,works related to roomrenovation,exposure to benzene,organic phosphates,radiation,alcohol (at least 2-3ounces per day for over one year)and smoking (half pack per day for over one year).The data was analyzed by chi-square test,t-test,logistic analysis for normaldistribution,nonparametric analysis for unnormal distribution using STATA7.0Results:The frequency of the-238 TNF1(G/G),TNF2(A/G andA/A)in BP2was78.3%,21.7% respectively.Logistic analysis shows:the frequency of the TNF-α-238TNF2 (A/G and A/A)was significantly increased in BP2 exposed to very highdosage benzene(average LTA=401.6 ppm-year).,compared to the control patientswith no MDS (OR=4.8,95%CI:1.13-20.2)The frequency of the TNF-α-308TNF1(G/G),TNF2(A/G andA/A)in BP with LTA＜60ppm was 77.8%,22.2%,Logistic analysis shows:the frequency of the TNF-α-308 TNF2 (A/G and A/A)inBP with LTA＜60ppm was significantly higher than in the B~+controls(OR=81.4,95CI:1.53-4327).Conclusion:This data suggests that individuals with TNF2 at-308nt are susceptible tobenzene poisoning exposed to low dosage benzene(LTA＜60ppm-year),while thosewith the TNF2 at-238nt have increased risk for benzene induced bone marrowdysplasia exposed to very high dosage benzene(average LTA=401.6 ppm-year).