| Background In recent years,an increasing trend in the prevalence of HT(Hashimoto’s thyroiditis,HT),has been observed in epidemiological studies.With the destruction of thyroid follicles,HT may lead to a variety of hypothyroid symptoms,including fatigue,weight gain and constipation.It is necessary to explore the etiology and pathogenesis of HT,which may provide important clues for disease prevention and therapy.It is well known that HT is a multifactorial disease resulting from the combination of genetic susceptibility and environmental factors.With the increase of iodine intake by universal salt iodization,much attention has been paid to the association between excess iodine intake and HT.However,the exact mechanisms by which excessive iodine intake induces HT are still unclear.Therefore,our study focused on excessive iodine intake,and investigated its effects on HT in Chinese population.On the other hand,we determined whether iodine induced HT through its interaction with the genetic susceptibility.Methods We conducted a case-control study with 731 HT patients and 992 healthy controls.All the participants completd a comprehensive survey that included a detailed questionaire and anthropometic measures.Urine samples were collected to test urinary iodine and urinary creatinine.Blood samples were collected to test high density lipoprotein cholesterol(HDL-C)、low density lipoprotein cholesterol(LDL-C)、triglyceride(TG)、total cholesterol(TC)、serum free triiodothyronine(FT3),serum free thyroxine(FT4),thyroid stimulating hormone(TSH),thyroid peroxidase antibody(TPOAb)and thyroglobulin antibody(TGAb).13 HT-associated SNPs were selected and genotyped for each subject,and we constructed “ s GRS ” and “ w GRS ” to account for the level of genetic susceptibility for each individual.Crude and multivariable logistic regression models are used to determine the associations of the urinary iodine levels and GRSs with the risk of HT.Restricted cubic spline regression was also applied to analyze the possible nonlinear relationship between urinary iodine and HT.The HT cases were further classified into euthyroid-HT and hypothyroidism-HT based on their thyroid function status,then crude and multinomial logistic regression models were performed to assess the association of urinary iodine with euthyroid-HT and hypothyroidism-HT,using the control as the reference group.The effects of interactions between the GRSs and urinary iodine on the risk of HT were tested by including the respective interaction terms in the models.Results 1.Association between excess iodine intake and Hashimoto’s thyroiditis All participants were divided into quartiles according to urinary iodine levels.Compared with the subjects in the first quartile,the odds of HT were 1.45(1.06-1.99)for those in the second quartile,1.66(1.17-2.34)for those in the third quartile,and 2.07(1.38-3.10)for those in the fourth quartile with adjustment for age,sex,BMI,education,high density lipoprotein cholesterol,low density lipoprotein cholesterol,triglyceride,total cholesterol and urine creatinine.With each 1-unit increase of log10-transformed urine iodine concentration,the odds of HT increased by 124%(adjusted OR = 2.24(1.53-3.28),P for trend < 0.001).The risk of HT has been increased by excess iodine nutrition(P for trend <0.001).Similar results were obtained in the crude model.Multivariable-adjusted restricted cubic spline analysis further demonstrated that the association between urinary iodine and HT risk was near linear(P-overall < 0.001;P-non-linear = 0.074).2.The effect of excessive iodine intake on hypothyroidism With adjustment for the above confounding factors,the levels of urinary iodine in the hypothyroidism group were higher than those in the euthyroid group(P for trend<0.05).Our findings indicate that each increment of urinary iodine was associated with a more than 2-fold increase in the odds of hypothyroidism-HT(adjusted OR = 2.64,95%CI = 1.73 to 4.05).Similar results were obtained in the unadjusted model.3.Association between genetic susceptibility and Hashimoto’s thyroiditis Logistic regression analyses produced ORs for HT across GRSs(s GRS and w GRS)quartiles.After adjusting for the above confounding factors,compared woith the subjects in the first GRS quartile,the odds of HT were 1.55(1.17-2.06)for those in the second quartile,1.85(1.33-2.57)for those in the third quartile,2.95(2.16-4.03)for those in the fourth quartile.For w GRS,the odds of HT were1.49(1.09-2.03)in the second quartile,2.17(1.59-2.96)in the third quartile,and 2.76(2.02-3.77)in the fourth quartile.The risk of HT has been increased by GRSs(adjusted OR = 1.19,95% CI=1.14 to 1.25 for each 1-point increase of s GRS,P for trend = 8.22×10-13;adjusted OR = 1.20,95% CI=1.14 to 1.26 for each 1-point increase of w GRS,P for trend = 1.40×10-13).Similar results were obtained in the crude model.4.The interaction of genetic susceptibility with excessive iodine intake to Hashimoto’s thyroiditis All participants were divided into quartiles according to GRSs(s GRS and w GRS).With adjustment for the above confounding factors,the risks of HT per increment of urinary iodine were not associated with genetic-susceptibility scores(Ps GRS for interaction = 0.400;Pw GRS for interaction = 0.799).Namely,the iodine-HT association is not modified by genetic susceptibility to HT.The similar results were observed in the crude model.Conclusion: Higher urinary iodine concentration was associated with increased risk of HT,and this association was near linear.Moreover,genetic susceptibility could increase the risk of HT,but had little effect on the iodine-HT association.Namely,there was no significant interaction between urinary iodine concentration and GRSs on the risk of HT.Interestingly,urinary iodine significantly increased the risk of hypothyroidism in the subgroup of HT patients with euthyroidism.Hence,urinary iodine levels should be controlled in this specific population to prevent hypothyroidism. |
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