Analysis of perchlorate exposure level and its effect on thyroid function in the population of Gansu
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摘要:
目的 对甘肃省人群高氯酸盐暴露水平进行评估并探讨其与甲状腺功能的关系，为该地区高氯酸盐污染防控提供依据。 方法 采用现况研究设计，选取兰州市城关区和定西市陇西县的随机两个社区中参与义诊的居民作为研究对象，采用问卷调查、体格检查和生化检查收集研究对象的基本资料及相关信息。应用多因素线性回归分析模型和限制性立方样条分析高氯酸盐暴露水平与甲状腺功能的关联及剂量-反应关系。 结果 本研究共纳入研究对象100名，包括男性48名和女性52名。尿高氯酸盐浓度的中位数(四分位间距)为23.90(13.30~43.54)μg/g Cr。多因素线性回归分析发现，调整混杂因素后，高氯酸盐暴露水平与血清总三碘甲状腺原氨酸(total triiodothyronine, TT3)、游离三碘甲状腺原氨酸(free triiodothyronine, FT3)和游离甲状腺素(free thyroxine, FT4)水平呈正相关趋势(均有P < 0.05)。限制性立方样条分析发现高氯酸盐暴露水平与血清TT3和FT4水平呈非线性剂量-反应关系(均有P < 0.05)。 结论 甘肃省地区人群的高氯酸盐暴露水平较高。高氯酸盐暴露水平与血清TT3、FT4水平有相关关联。 Abstract:Objective To explore the association between perchlorate exposure level and thyroid function in the population of Gansu, in order to provide a basis for the prevention and control of perchlorate pollution in the region. Methods Using the cross-sectional study design, residents who participated in voluntary clinic in two random communities in Chengguan District, Lanzhou City and Longxi County, Dingxi City, Gansu Province were selected as the subjects of this study, and questionnaires, physical and biochemical examinations were used to collect basic data and relevant information of the subjects. The multivariate linear regression and restricted cubic spline model were used to analyze the association and dose-response relationship between perchlorate exposure levels and thyroid function. Results A total of 100 subjects were included in the study, including 48 males and 52 females. The median average exposure level (quartile spacing) of urinary perchlorate was 23.90 (13.30-43.54) μg/g Cr. The results of multivariate linear regression analysis revealed that after adjusting the confounding factors, the level of perchlorate exposure was positively correlated with the level of serum total triiodothyronine (TT3), free triiodothyronine (FT3) and free thyroxine (FT4) levels (all P < 0.05). The restrictive cubic spline model analysis indicated a non-linear dose-response correlation between perchlorate exposure levels with serum total triiodothyronine and free thyroxine levels (all P < 0.05). Conclusions The population in Gansu has a high level of perchlorate exposure. There is a correlation between perchlorate exposure levels and serum total triiodothyronine and free thyroxine levels. -
Key words:
- Perchlorate /
- Exposure /
- Thyroid function /
- Adult /
- Gansu
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图 1 基于限制性立方样条分析高氯酸盐暴露水平与甲状腺相关激素的剂量-反应关系
注：甲状腺相关激素：A，TT3；B，TT4；C，FT3；D，FT4；E，TSH。调整的混杂因素：性别、年龄、BMI类型、居住时长、职业类型、TGAb和TPOAb。
Figure 1. Dose-response relationship between perchlorate exposure and thyroid-related hormones based on restricted cubic splines
表 1 尿液生化指标和血清甲状腺相关激素的基本情况
Table 1. Urine biochemical indicators and basic conditions of serum thyroid-related hormones
指标 x±s(n=100) 最小值 百分位数 最大值 25th 50th 75th 尿高氯酸盐(g/L) 24.81±21.31 3.69 15.16 20.06 28.37 154.47 尿碘(g/L) 190.10±95.04 38.90 110.63 193.69 250.41 488.90 尿肌酐(g/L) 1.04±0.47 0.24 0.73 1.01 1.28 2.22 尿高氯酸盐a(μg/g Cr) 37.85±61.24 4.01 13.30 23.90 43.54 568.29 尿碘a(μg/g Cr) 216.51±112.15 48.03 138.46 195.87 280.58 536.34 血清TT3(ng/mL) 1.60±0.37 0.70 1.37 1.65 1.84 2.46 血清TT4(ng/mL) 79.67±13.00 39.90 71.75 79.35 88.80 110.70 血清FT3(pg/mL) 3.31±0.37 2.46 3.15 3.30 3.54 4.86 血清FT4(pg/mL) 10.57±1.31 6.90 9.80 10.70 11.43 13.60 血清TSH(uIU/mL) 3.09±1.31 1.01 2.27 2.97 3.80 8.79 注：a表示经尿肌酐调整后的尿高氯酸盐值和尿碘值; 缩略词：TT3，总三碘甲状腺原氨酸；TT4，总甲状腺素；FT3，游离三碘甲状腺原氨酸；FT4，游离甲状腺素；TSH，促甲状腺激素。下同。 
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表 2 不同基线特征下血清甲状腺相关激素水平的分布情况
Table 2. Distribution of serum thyroid-related hormone levels by baseline characteristics
分组 例数(n) TT3(ng/mL) (x±s) TT4(ng/mL) (x±s) FT3(pg/mL) (x±s)/ [M(P25, P75)] FT4(pg/mL) (x±s) TSH(uIU/mL) (x±s)/ [M(P25, P75)] 地区 城关区 20 1.05±0.17 81.67±16.31 3.00±0.42 9.51±1.55 3.14(2.53, 4.01) 陇西县 80 1.74±0.25 79.17±12.10 3.39±0.31 10.83±1.10 2.94(2.24, 3.53) 检验统计量 t=11.509 t=-0.769 t=4.626 t=3.599 Z=-0.913 P值 0.001 a 0.444 0.001 a 0.001 a 0.361 性别 男 48 1.69±0.39 81.46±13.58 3.52(3.35, 3.64) 10.86±1.21 2.77(2.07, 3.40) 女 52 1.51±0.33 78.02±12.34 3.22(2.90, 3.30) 10.30±1.35 3.09(2.41, 4.04) 检验统计量 t=-2.535 t=-1.328 Z=-5.617 t=-2.178 Z=-1.235 P值 0.013 b 0.187 0.001 a 0.032 b 0.217 年龄(岁) ≤30 23 1.48±0.38 82.76±11.28 3.36±0.44 10.95±1.10 2.51(1.61, 3.06) 31~45 60 1.63±0.35 77.51±13.61 3.30±0.34 10.45±1.38 3.01(2.47, 4.05) ＞45 17 1.65±0.40 83.11±11.98 3.29±0.38 10.48±1.30 3.14(2.46, 4.09) 检验统计量 F=1.688 F=2.123 F=0.298 F=1.305 H=6.722 P值 0.190 0.125 0.743 0.276 0.035 b 居住时长(年) < 5 6 1.23±0.41 84.87±6.24 3.17±0.34 10.48±1.09 2.79(1.70, 3.16) 5~ < 20 29 1.58±0.39 80.89±15.78 3.35±0.28 10.62±1.09 3.09(2.25, 4.15) 20~ < 35 30 1.60±0.36 79.38±11.63 3.28±0.34 10.56±1.66 3.10(2.22, 3.97) ≥35 35 1.68±0.31 78.01±12.52 3.34±0.31 10.54±1.22 2.75(2.35, 3.45) 检验统计量 F=5.555 F=1.655 F=0.426 F=0.019 H=1.357 P值 0.020 b 0.201 0.516 0.891 0.716 职业类型 在校学生 10 1.17±0.29 89.13±11.13 3.28±0.33 10.72±1.25 2.60(2.17, 3.16) 家务、待业人员 19 1.76±0.23 82.19±15.52 3.40±0.27 10.66±0.99 3.09(2.78, 4.23) 事业单位、商业人员 26 1.76±0.28 80.08±10.92 3.40±0.24 11.32±1.10 2.70(2.18, 3.40) 农林、技术人员 45 1.53±0.38 76.26±12.38 3.24±0.35 10.06±1.36 2.98(2.02, 4.01) 检验统计量 F=1.725 F=9.450 F=3.355 F=4.439 H=3.678 P值 0.167 0.003 b 0.022 b 0.038 b 0.298 受教育程度 小学及以下 32 1.62±0.39 81.53±13.52 3.36±0.41 10.61±1.26 3.37±1.66 初中 40 1.58±0.40 78.88±13.58 3.31±0.36 10.52±1.24 2.82±1.05 高中/中专 13 1.53±0.36 79.65±12.91 3.21±0.44 10.42±0.88 3.38±1.42 大学及以上 15 1.66±0.22 77.79±10.93 3.22±0.24 10.75±1.11 2.97±0.86 检验统计量 F=0.347 F=0.366 F=0.475 F=0.177 F=1.317 P值 0.791 0.778 0.700 0.912 0.273 BMI(kg/m2) 正常 48 1.59±0.41 81.53±14.95 3.33±0.33 10.61±1.36 2.96(2.47, 3.44) 超重 34 1.60±0.30 76.00±10.02 3.29±0.27 10.40±1.43 3.10(2.25, 4.12) 肥胖 18 1.63±0.36 81.62±11.42 3.32±0.36 10.78±0.89 2.41(1.87, 3.84) 检验统计量 F=0.156 F=0.305 F=0.026 F=0.041 H=1.857 P值 0.694 0.582 0.872 0.840 0.395 TGAb(ng/mL) ≤4(阴性) 91 1.58±0.38 80.07±13.22 3.31±0.38 10.56±1.35 2.95(2.23, 3.81) ＞4(阳性) 9 1.78±0.14 75.56±10.14 3.36±0.15 10.62±0.86 3.02(2.55, 3.51) 检验统计量 t=-3.032 t=0.995 t=-0.897 t=-0.132 Z=-0.584 P值 0.006 b 0.322 0.380 0.895 0.559 TPOAb(IU/mL) ≤9(阴性) 96 1.61±0.37 80.13±12.90 3.33±0.36 10.62±1.27 2.95(2.24, 3.64) ＞9(阳性) 4 1.43±0.35 68.50±11.27 2.97±0.43 9.25±1.69 3.52(3.01, 4.08) 检验统计量 t=0.967 t=1.773 t=1.951 t=2.088 Z=-1.152 P值 0.336 0.079 0.054 0.039 b 0.249 注：a表示P＜0.001；b表示0.001＜P＜0.05。
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表 3 尿高氯酸盐与血清甲状腺相关激素的关联性分析
Table 3. Correlation analysis between urinary perchlorate and serum thyroid-related hormones
变量 例数(n) TT3 β(95% CI) TT4 β(95% CI) FT3 β(95% CI) FT4 β(95% CI) Ln (TSH) β(95% CI) 模型1 合计 100 0.132(0.052, 0.212) a -0.831(-3.804, 2.141) -0.004(-0.075, 0.068) 0.153(-0.145, 0.452) 0.028(-0.066, 0.122) 尿碘(g/L) ≥100 79 0.149(0.054, 0.244) a -0.176(-3.521, 3.168) 0.007(-0.076, 0.091) 0.261(-0.093, 0.615) 0.038(-0.068, 0.144) < 100 21 0.002(-0.153, 0.157) -3.546(-11.895, 4.802) -0.087(-0.254, 0.081) -0.568(-1.101, -0.035) a 0.040(-0.225, 0.306) 性别 男 48 0.212(0.103, 0.320) b -1.344(-5.723, 3.034) 0.059(-0.022, 0.141) 0.052(-0.341, 0.444) 0.036(-0.123, 0.195) 女 52 0.118(0.004, 0.231) a 0.906(-3.556, 5.367) 0.034(-0.064, 0.133) 0.505(0.038, 0.972) a -0.008(-0.125, 0.109) 模型2 合计 100 0.162(0.084, 0.240) b -0.279(-3.400, 2.842) 0.051(-0.012, 0.114) 0.293(-0.008, 0.593) 0.001(-0.095, 0.097) 尿碘(g/L) ≥100 79 0.177(0.083, 0.270) b 0.403(-3.109, 3.915) 0.061(-0.013, 0.135) 0.420(0.072, 0.770) a 0.010(-0.099, 0.119) < 100 21 0.027(-0.124, 0.177) -3.209(-12.685, 6.267) -0.032(-0.194, 0.129) -0.615(-1.242, 0.013) 0.009(-0.259, 0.277) 性别 男 48 0.198(0.086, 0.310) b -1.220(-5.714, 3.689) 0.061(-0.025, 0.146) 0.145(-0.246, 0.537) 0.000(-0.158, 0.159) 女 52 0.116(0.001, 0.232) a 0.942(-3.606, 5.489) 0.035(-0.064, 0.135) 0.508(0.031, 0.984) a -0.008(-0.125, 0.110) 模型3 合计 100 0.170(0.093, 0.247) b 1.124(-1.965, 4.213) 0.076(0.015, 0.136) a 0.403(0.107, 0.700) a -0.001(-0.102, 0.100) 尿碘(g/L) ≥100 79 0.175(0.085, 0.265) b 1.282(-2.286, 4.850) 0.083(0.013, 0.154) a 0.512(0.167, 0.858) a 0.015(-0.101, 0.131) < 100 21 0.020(-0.175, 0.216) -5.020(-15.171, 5.131) -0.031(-0.262, 0.201) -0.768(-1.644, 0.107) 0.030(-0.312, 0.373) 性别 男 48 0.184(0.065, 0.302) a 0.404(-4.197, 5.005) 0.080(-0.009, 0.169) 0.167(-0.251, 0.585) -0.014(-0.182, 0.155) 女 52 0.142(0.035, 0.249) a 2.383(-2.171, 6.938) 0.069(-0.020, 0.158) 0.703(0.275, 1.132) a -0.017(-0.135, 0.102) 注：模型1未调整混杂因素；模型2调整了年龄和BMI类型；模型3调整了年龄、BMI类型、居住时长、职业类型、TGAb和TPOAb。a表示0.001＜P＜0.05，b表示P＜0.001。
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