The Correlation between Vitamin D Receptor Gene Bg1I and Cdx-2 Polymorphism and Hashimoto’ s Thyroiditis
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摘要:
目的 探讨VDR基因Bg1I、Cdx-2多态性与桥本氏甲状腺炎（hashimoto’ s thyroiditis，HT）的相关性。 方法 应用TaqMan 荧光探针技术，对178例HT组，其中甲功正常（H0）组56例，亚临床甲减（H1）组80例，甲减（H2）组42例和64例健康对照者（NT）组的VDR基因Bg1I、Cdx-2位点SNP进行检测，比较和分析各组间基因型频率、等位基因频率以及相关临床资料。 结果 （1）Bg1I位点GG、GT、TT基因型分布频率分别为0.500，0.405和0.095 ，等位基因G、T分布频率分别为0.7025和0.2975；Cdx-2位点GG、GA、AA基因型分布频率分别为0.2934，0.5289 和0.1777，等位基因G及A分布频率分别为0.5579及0.4421；（2）NT及HT组间各等位基因频率及基因型分布，差异无统计学意义（P > 0.05）；（3）Logistic回归分析表明25（OH）D缺乏可能是HT发生的独立危险因素（OR = 1.573，P = 0.046）；（4）男性（OR = 0.158，P < 0.001）及Cdx-2位点G等位基因（OR = 0.301，P = 0.035）可能是HT患者发生甲减的保护因素，高滴度TPO-Ab（OR = 1.639，P = 0.045）及TG-Ab（OR = 1.779，P = 0.007）可能是其危险因素。 结论 （1）VDR Bg1I、Cdx-2位点存在单核苷酸多态性。（2）Cdx-2位点G等位基因可能是HT发生甲减的保护因素；（3）Bg1I位点SNP与HT的发生及进展无关。 Abstract:Objective To investigate the correlation between Vitamin D receptor gene Bg1I, Cdx-2 polymorphism with Hashimoto’ s thyroiditis （HT）. Methods The SNP of VDR gene Bg1I and CDX-2 in 178 HT patients were detected by TaqMan fluorescent probe, including 56 patients with normal thyroid function （H0 group）, 80 patients with subclinical hypothyroidism （H1 group）, 42 patients with hypothyroidism （H2 group） and 64 healthy controls （NT group）. The genotype frequency, allele frequency and related clinical data were compared and analyzed. Results Bg1I GG, GT and TT genotypes frequencies were 0.500, 0.405 and 0.095, respectively; alleles G and T were 0.7025 and 0.2975, respectively. CDX-2 GG, GA and AA genotypes frequencies were 0.2934, 0.5289 and 0.1777, respectively; alleles G and A frequencies were 0.5579 and 0.4421, respectively. The genotype frequency and allele frequency in two groups were not significantly different （P > 0.05）. Logistic regression analysis indicated 25 （OH） D deficiency might be an independent risk factor for HT （OR = 1.573, P = 0.046）; male （OR = 0.158, P < 0.001） and CDX-2 G genotype （OR = 0.301, P = 0.035） may be protective factors for hypothyroidism in HT patients. High titrate TPO-Ab （OR = 1.639, P = 0.045） and TG-Ab （OR = 1.779, P = 0.035） may be risk factors for hypothyroidism in HT patients. Conclusion （1）Single nucleotide polymorphisms （SNPs） were found at VDR BG1I and CDX-2 sites. （2）CDX-2 G genotype may be a protective factor of hypothyroidism in HT. （3）Bg1I single nucleotide polymorphism was not related to the occurrence and progression of HT. -
表 1 组间临床资料的比较[（
$\bar x \pm s $ ）或M（P25，P75）]（1）Table 1. Comparison of clinical data among different groups [（
$\bar x \pm s $ ）or M（P25，P75）]组别 n 性别（男/女） 年龄/岁 25（OH）D/（ng/mL） TT3/（ng/dL） TT4/（μg/dL） FT3/（pg/mL） NT组 64 13/51 39.66 ± 12.58 20.17 ± 6.95 102.20（90.33，116.00） 8.11（6.26，9.60） 2.78（2.57，3.08） HT组 178 24/154 45.02 ± 13.02* 17.49 ± 7.28* 101.50（80.60，122.00） 7.37（5.58，9.08） 2.77（2.40，3.02） HT0组 56 2/54 43.43 ± 12.71 18.68 ± 7.77 104.50（89.20，122.75） 8.31（6.97，10.31） 2.81（2.60，3.04） HT1组 80 9/71 45.48 ± 12.83* 17.15 ± .34* 103.17（86.83，125.75） 7.61（6.45，9.15） 2.85（2.52，3.20） HT2组 42 13/29 46.29 ± 13.90 16.55 ± 6.38* 81.40（61.23，100.20）*△☆ 3.67（0.93，5.98）*△☆ 2.05（1.00，2.53）*△☆ 与NT组相比，*P < 0.05；与HT0组相比，△P < 0.05；与HT1组相比，☆P < 0.05。 
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表 1 组间临床资料的比较（
$\bar x \pm s $ ）或M（P25，P75）（2）Table 1. Comparison of clinical data among different groups （
$\bar x \pm s$ ） or M（P25，P75）组别 n FT4
/（ng/dL）TSH
/（mIU/L）TPO-Ab
/（IU/mL）TG-Ab
/（IU/mL）NT组 64 1.16（1.08，1.26） 2.01（1.49，2.70） 3.31（1.90，7.27） 13.33（10.54，25.75） HT组 178 1.01（0.79，1.23）* 5.52（2.93，16.78）* 334.75（36.40，16.37）* 285.55（88.29，936.80）* HT0组 56 1.17（0.98，1.36） 1.89（1.57，2.72） 47.52（27.49，426.00）* 130.45（24.21，362.13）* HT1组 80 1.09（0.91，1.26）*△ 5.98（4.61，9.78）*△ 360.67（74.13，1175.25）*△ 313.55（121.55，821.20）*△ HT2组 42 0.55（0.29，0.71）*△ 62.95（26.81，100.00）*△☆ 1666.00（92.48，2001.43）*△☆ 858.65（254.58，3449.21）*△ 与NT组相比，*P < 0.05；与HT0组相比△P < 0.05；与HT1组相比☆P < 0.05。
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表 2 2组25（OH）D状况比较[n（%）]
Table 2. Comparison of 25（OH）D level between two groups [n（%）]
组别 n 充足 不足 缺乏 NT组 64 4（6.25） 28（43.75） 32（50.00） HT组 178 12（6.74） 44（24.72） 122（68.54） Z 2.799 P 0.005
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表 3 各组间VDR基因Bg1I位点SNP频率[n（%）]
Table 3. VDR gene Bg1I among each group [n（%）]
组别 n 基因型 等位基因 GG GT TT G T Totle 242 121（50.00） 98（40.50） 23（9.50） 340（70.25） 144（29.75） NT 64 27（42.19） 32（50.00） 5（7.81） 86（67.19） 42（32.81） HT 178 94（52.81） 66（37.08） 18（10.11） 254（71.35） 102（28.65） HT0 56 34（60.71） 16（28.58） 6（10.71） 84（75.00） 28（25.00） HT1 80 37（46.25） 37（46.25） 6（7.50） 111（69.38） 49（0.62） HT2 42 23（54.76） 13（30.95） 6（14.29） 59（70.24） 25（29.76）
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表 4 各组间VDR基因Cdx-2位点SNP频率[n（%）]
Table 4. VDR gene Cdx-2 among each group [n（%）]
组别 n 基因型 等位基因 GG GA AA G A Totle 242 71（29.34） 128（52.89） 43（17.77） 270（55.79） 214（44.21） NT 64 18（28.12） 38（59.38） 8（12.50） 74（57.81） 54（42.19） HT 178 53（29.78） 90（50.56） 35（19.66） 196（55.06） 160（44.94） HT0 56 20（35.71） 25（44.65） 11（19.64） 65（58.04） 47（41.96） HT1 80 24（30.00） 38（47.50） 18（22.50） 86（53.75） 74（46.25） HT2 42 9（21.43） 27（64.29） 6（14.28） 45（53.57） 39（46.43）
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表 5 HT发生危险因素的Logistic回归分析
Table 5. The logistic regression analysis of HT risk factors
自变量 B S.E. Wals df P OR 95%CI 下限 上限 常量 0.328 0.371 0.786 1 0.375 1.389 25（OH）D缺乏 0.453 0.227 3.977 1 0.046 1.573 1.008 2.456
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表 6 HT甲减发生危险因素的Logistic回归分析
Table 6. The logistic regression analysis of risk factors for Hypothyroidism in HT group
自变量 B S.E. Wals df P OR 95%CI 下限 上限 常量 −0.083 1.529 0.003 0.957 0.920 男性 −1.844 0.530 12.119 1 < 0.001 0.158 0.056 0.447 Cdx-2-G等位基因 −1.201 0.568 4.464 1 0.035 0.301 0.099 0.917 TPO-Ab 0.494 0.246 4.027 1 0.045 1.639 1.012 2.655 TG-Ab 0.576 0.215 7.183 1 0.007 1.779 1.167 2.711
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