The Association Of Bisphenol A And Its Interaction With The Genetic Predisposition With Hashimoto’s Thyroiditis And Thyroid Nodules In The Chinese Population

As a well-known endocrine disrupter,bisphenol A（BPA）is widely used to produce epoxy resins and polycarbonate plastics.BPA exposure is essentially continuous and ubiquitous in humans.In recent years,an increasing trend in the prevalence of thyroid diseases,especially Hashimoto’s thyroiditis（HT）and thyroid nodules（TNs）,has been observed in epidemiological studies.Exploring the environmental risk factors associated closely with these thyroid diseases may provide important clues for disease prevention.Therefore,our study focused on BPA,and investigated its effects on HT as well as TNs in Chinese population,aiming at contributing to the promotion of the regulations for BPA in future.HT is a complex disease determined by both environmental and genetic factors,but the exact mechanisms responsible for the disease development are still largely unknown.Determining whether BPA induced HT in the individuals with specific genetic background,or whether BPA induced HT through interacting with the genetic predisposition,may provide new insights into the aetiology and pathogenesis of HT from the genetic perspective.We further focused on HT genetic predisposition and explored in-depth its interaction with BPA on HT risk.The main findings are as follows:1.Association between bisphenol A exposure and Hashimoto’s thyroiditisAims We explored the association of urinary BPA with HT risk and thyroid antoantibodies levels in Chinese population.Methods A case-control study was conducted comprising 729 HT patients and 991healthy controls.Urinary total BPA（free and conjugated）concentration was quantified using the modified HPLC-MS/MS analytical method.The creatinine-adjusted BPA（μg/g creatinine）was calculated by dividing urinary BPA（μg/L）by urinary creatinine concentration（g/L）to correct for the degree of urine dilution.Results All participants were divided into quartiles according to urinary BPA levels.Compared with the subjects in the first quartile,the odds of HT was 2.55（95%CI:1.82-3.56）for those in the second quartile,3.50（95%CI:2.51-4.89）for those in the third quartile,and 5.31（95%CI:3.78-7.46）for those in the fourth quartile with adjustment for age,sex,BMI,education,HDL-C,LDL-C,triglyceride,total cholesterol and urinary iodine.With each unit increase of log₁₀-transformed urine BPA concentration,the odds of HT increased by 246%（adjusted OR=3.46;95%CI=2.69-4.45,P<0.001）.The multiple linear regression analysis adjusted for potential confounders demonstrated that urinary BPA was positively associated with both TPOAb（β=0.17,95%CI=0.05-0.28,P<0.001）and TGAb（β=0.17,95%CI=0.10-0.25,P<0.001）.Conclusions Our findings indicate that BPA exposure was significant associated with HT risk and thyroid autoantibodies levels in Chinese polulation.2.The interaction of bisohenol A with the genetic predisposition to Hashimoto’s thyroiditis in Han Chinese populationAims We examined whether urinary BPA interacts with the genetic predisposition to HT in Chinese Han population.Methods A case-control study was conducted comprising 729 HT patients and 991healthy controls.Urinary total BPA（free and conjugated）concentration was quantified using the modified HPLC-MS/MS analytical method.The creatinine-adjusted BPA（μg/g creatinine）was calculated by dividing urinary BPA（μg/L）by urinary creatinine concentration（g/L）to correct for the degree of urine dilution.13 HT-associated loci were selected and genotyped using fast TaqMan assays.Moreover,we constructed a weighted genetic risk score（wGRS）to account for the level of genetic predisposition for each individual,assuming that each loci in the panel acts independently and contributes to the risk of HT in an additive manner.Results All participants were divided into quartiles according to wGRS.With adjustment for age,sex,BMI,education,HDL-C,LDL-C,triglyceride,total cholesterol and urinary iodine,the risks of HT per increment of urinary BPA were 2.48（95%CI:1.48-4.14）for the first quartile,2.26（95%CI:1.38-3.71）for the second quartile,5.26（95%CI:3.02-9.15）for the third quartile,and 6.08（95%CI:3.47-10.67）for the fourth quartile（P=0.018 for interaction）.For the same categories of wGRS,the increases in TGAb per increment of urinary BPA were 0.11,0.12,0.23 and 0.24,respectively（P=0.012 for interaction）;the increases in TPOAb per increment of urinary BPA were 0.09,0.11,0.24and 0.22,respectively（P=0.004 for interaction）.Conclusions Our findings indicate that the association of BPA with HT risk and thyroid autoantibodies appeared to be more pronounced in population with a higher genetic predisposition to HT.3.Bisphenol A exposure and risk of thyroid nodules in Chinese WomenAims We aimed to examine the association between urinary BPA and TNs in women who are more susceptible to TNs.Methods A case-control study was conducted comprising 1416 Chinese women（705cases and 711 controls）.All participants underwent thyroid ultrasonography.Urinary total BPA（free and conjugated）concentration was quantified using the modified HPLC-MS/MS analytical method.The creatinine-adjusted BPA（μg/g creatinine）was calculated by dividing urinary BPA（μg/L）by urinary creatinine concentration（g/L）to correct for the degree of urine dilution.Results All participants were divided into quartiles according to urinary BPA levels.Compared with women in the first quartile,the odds of TNs was 72%（adjusted OR=1.72,95%CI:1.25 to 2.35）higher for those in the second quartile,54%（adjusted OR=1.54,95%CI:1.12 to 2.12）higher for those in the third quartile,and 108%（adjusted OR=2.08,95%CI:1.50 to 2.90）higher for those in the fourth quartile after adjusting for age,BMI,education,HDL-C,LDL-C,triglyceride,total cholesterol,urinary iodine,TGAb and TPOAb.When the study population was stratified into thyroid autoantibody positive group and thyroid autoantibody negative group,we found that only in the positive group,the association was significant（OR=3.71;95%CI=2.36-5.83）.Multivariable-adjusted restricted cubic spline analysis demonstrated a similar result that in the thyroid autoantibody positive group,the association between urinary BPA and TNs risk was near linear（P-overall<0.001;P-non-linear=0.054）.Conclusions In Chinese women,higher urinary BPA concentration was associated with increased risk of TNs only in those with positive thyroid autoantibodies.Moreover,this association was near linear,indicating that any rise in BPA exposure was associated with elevated TNs risk.