| Part 1 Epidemiological survey of iodine nutrition status in shcoolchildren aged 8~10 years-old of Wuqiao county of Hebei provinceObjective: The present study was conducted to assess the iodine levels in external environment and the iodine nutrition status among schoolchildren (8~12 yrs) of Wuqiao county of Hebei province.Methods: Five small towns were selected randomly according to directions of east, west, south, north and center of Wuqiao county and then 5 villages were selected randomly according to directions of east, west, south, north and center of each selected town respectly. Drinking water samples and salt samples were gotten from each selected village. Iodine content in Drinking water samples were determined by Arsenic cerium catalytic spectrophotometry and that in salt samples were determined by direct titrimetric methods. Then 1209 schoolchildren, aged 8~12 years were selected by multistage random sampling from the selected towns. Thyroid size was estimated in each child by inspection and palpation and was graded according to the criteria recommended by WHO. Urinary iodine concentration (UIC) was also measured by (NH4)2S2O8 digesting As3+-Ce4+ catalyzing spectrophotometry in 584 schoolchildren as well as T4 and TSH was measured by Radio Immunoassay(RIA) in 218 schoolchildren.Results: (1) The median of drinking water iodine Concentration in 67 samples was 107.05μg/l (Range: 23.54~560.67μg/l). 43.28% of total water samples had iodine level below 100μg/l. 23.88% of samples had iodine level between 100 and 150μg/l , 16.42% had iodine level between 150and 300μg/l and 16.42% had iodine level more than 300μg/l. There were no samples had iodine level below 10μg/l. (2) The median of salt iodine Concentration in 250 samples was 26.86mg/kg (Range: 0.73~45.35mg/kg). 22.8% of total salt samples had iodine level below <5mg/kg. 5.2% of samples had iodine level between 5 and 20mg/kg, 72.0% of samples had iodine level between 20and 50 mg/kg. In this area, iodized-salt covering rate, iodized-salt qualified rate and consumption rate of qualified iodized-salt was 77.2%, 93.3% and 72.0% respectly. (3) Over all, 74 students had goiter (grade I: 72; grade II: 2) and the goiter prevalence was 6.1% in the studied region. Goiter prevalence also showed positive correlation significantly with median of drinking water iodine (P=0.037). (4) The median UIC was 208.36μg/l (Range: 4.06~1886.33μg/l). 18.5% of 584 samples had iodine excretion level below 100μg/l and 4.6% had iodine level below 50μg/l. 27.7% of subjects had UIC between 100 and 199μg/l, 27.2% had UIC between 200 and 299μg/l and 26.5% had UIC more than 300μg/l. According to UIC, there was not significant different in goitrous and nongoitrous children (224.98μg/L vs 206.78μg/L, P=0.241). There was significant positive correlation between median of UIC and that of drinking water iodine in the selected towns(P=0.037). (5) 25 subjects had abnormal thyroid function and the prevalence of that was 11.5%. 72% of the children with abnormal thyroid function was subclinical hypothyroidism and 24% was subclinical hyperthyroidism. According to the prevalence of abnormal thyroid function, there was not significant different in goitrous and nongoitrous children (20% vs 10.8%, P=0.513).Conclusion: There are some iodine excess areas in wuqiao county. Iodine nutrition of shcoolchildren in this area is excessive relatively according to the results of median UIC, goiter prevalence and thyroid function. Drinking water excess iodine may be the principal cause for the excessive iodine nutrition. People should stop consuming iodined salt in the iodine excess areas.Part 2 Association of cytokine (TNF-α, IFN-γ) polymorphisms with endemic goiterObjective: To explore the possible association of the polymorphisms of TNF-α-238/TNF-α-419/IFN-γ+874 with endemic goiter. Methods: The DNA samples of 146 controls and 74 endemic goiter patients were selected to identify SNPs in TNF-α-238, TNF-α-419 and IFN-γ+874. SNPs in the three loci were screened by high resolution melting(HRM) and DNA sequencing. TNF-α-238, TNF-α-419 and IFN-γ+874 SNP was genotyped by case-control method to analysis their genetic association with endemic goiter.Results: (1) Only GG and GA genotypes were detected in TNF-α-238. The genotype GA and allele A of TNF-α-238 were associated with endemic goiter(X2=6.714, P=0.010; X2=6.152, P=0.013, respectively). Contrast the genotype GG, GA arriers were at an inereased risk of goiter with an odds ratio 2.61 (95% Cl: 1.24~5.49). Contrast the allele G, A allele was a risk allele of goiter(OR=2.39, 95%Cl: 1.18~4.83) (2) Only GG and GA genotypes were detected in TNF-α-419. There were no significant associations of TNF-α-419 genotype and allele frequency with endemic goiter (X2=0.091, p=0.763; X2=0.083, p=0.773, respectively). (3) Only TT and TA genotypes were detected in IFN-γ+874. The genotype TA and allele A of T IFN-γ+874 were associated with endemic goiter(X2=4.944, p=0.026; X2=4.209, p=0.040, respectively). Contrast the genotype TT, TA arriers were at an inereased risk of goiter with an odds ratio 2.01 (95%Cl: 1.08~3.74). Contrast the allele T, A allele was a risk allele of goiter(OR=1.79, 95%Cl: 1.02~3.15).Conclusion: TNF-α-238 GA genetic polymorphism is associated with endemic goiter. GA genotype may be a risk genotype and A allele may be a susceptible gene of endemic goiter. The TNF-α-419 SNP is not associated with endemic goiter,it may not contribute to genetic predisposition to endemic goiter. IFN-γ+874 TA genetic polymorphism is associated with endemic goiter. TA genotype may be a risk genotype and A allele may be a susceptible gene of endemic goiter.Part 3 Association of growth factor (IGF-1,TGF-β1) polymorphisms with endemic goiterObjective: To investigate the possible association of the polymorphisms of IGF-1-1245/TGF-β1-509 with endemic goiter.Methods: The DNA samples of 146 controls and 74 endemic goiter patients were selected to identify SNPs in IGF-1-1245 and TGF-β1-509. SNPs in the two loci were screened by high resolution melting(HRM) and DNA sequencing. IGF-1-1245 and TGF-β1-509 SNP was genotyped by case-control method to analysis their genetic association with endemic goiter.Results: (1) AA, GA and GG genotypes were detected in IGF-1-1245. The polymorphysms of IGF-1-1245 were associated significantly with endemic goiter(X2=10.046, P=0.007). Contrast the GG genotype, AA and GA arriers were at an inereased risk of goiter(additive model: AA:OR=3.91, OR 95%CI=1.39~11.0, GA:OR=2.03, OR95%CI=1.08~3.81; dominant model: OR=2.35, OR95%CI=1.31~4.19; recessive model: OR=3.10, OR95%CI =1.13~8.52). Contrast the allele G, A allele was a risk allele of goiter(OR=2.24, OR95%CI=1.41~3.56, p=0.001). (2) AA, GA and GG genotypes were detected in TGF-β1-509. There were no significant associations of TGF-β1-509 genotype and allele frequency with endemic goiter (X2=1.819, P=0.403, X2=0.280, P=0.149, respectively).Conclusion: IGF-1-1245 polymorphisms is associated with endemic goiter. AA and GA genotypes may be risk genotypes and A allele may be a susceptible gene of endemic goiter. The TGF-β1-509 SNP is not associated with endemic goiter,it may not contribute to genetic predisposition to endemic goiter.Part 4 Gene-environmental interaction in endemic goiterObjective: To analyse the interaction of gene-gene and gene-environment in endemic goiter.Methods: Independent risk factors of endemic goiter were selected from TNF-α-238, TNF-α-419, IFN-γ+874, IGF-1-1245, TGF-β1-509 and iodine excessive nutrition by univariate analysis and multivariate analysis. Then the interaction of SNPs and iodine nutrition in endemic goiter was analysed by case-only study and crossover atudy at the same time. The ORint was used as evaluation index of interaction in case-only study. And the synergy index(S), attributable proportion of interaction(API), pure attributable proportion of interaction(AP*) and relative excess risk of interaction(RERI) were used as evaluation indexes of interaction in crossover study.Results: (1) With univariate analysis, the factors associated with endemic goiter significantly included TNF-α-238 GA, IFN-γ+874 TA, IGF-1-1245 AA/GA and iodine excessive nutrition. (2) With multivariate analysis, IFN-γ+874 TA, IGF-1-1245 AA/GA and iodine excessive nutrition entered unconditional logistics regression model finally. (3) With case-only study, the interaction of IFN-γ+874 TA and IGF-1-1245 AA/GA was not found in endemic goiter(ORint=0.53, 95%CI: 0.20~1.40); the interaction of IFN-γ+874 TA and iodine excessive nutrition was not found in endemic goiter(ORint=1.56, 95%CI: 0.59~4.13); and there was no interaction between IGF-1-1245 AA/GA and iodine excessive nutrition in endemic goiter too(ORint=0.78, 95%CI: 0.31~1.98). (4) With crossover study, the interaction of IFN-γ+874 TA and IGF-1-1245 AA/GA was not found in endemic goiter(S =0.70, API=-0.31, AP*=-0.42, RERI =-1.17); but the interaction of IFN-γ+874 TA and iodine excessive nutrition was found in endemic goiter(S =5.55, API=0.72, AP*=0.82, RERI =6.24), and at the same time the interaction of IGF-1-1245 AA/GA and iodine excessive nutrition was found in endemic goiter(S =2.51, API=0.53, AP*=0.60, RERI =4.14).Conclusion: IFN-γ+874 TA, IGF-1-1245 AA/GA and iodine excessive nutrition are the independent risk factors of endemic goiter. In multiplicative model, the interaction of IFN-γ+874 TA and IGF-1-1245 AA/GA is not associated with endemic goiter , the interaction of IFN-γ+874 TA and iodine excessive nutrition is not associated with endemic goiter and the interaction of IGF-1-1245 AA/GA and iodine excessive nutrition is not associated with endemic goiter too. In additive model, the interaction of IFN-γ+874TA and IGF-1-1245AA/GA is not associated with endemic goiter, but the interaction of IFN-γ+874 TA and iodine excessive nutrition is associated with endemic goiter and that of IGF-1-1245 AA/GA and iodine excessive nutrition is also associated with endemic goiter. |
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