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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[1] Dana L, Mincer, Ishwarlal Jialal. Hashimoto thyroiditis[EB/OL]. [2020-08-10][2021-04-25]. http://creativecommons.org/licenses/by/4.0. [2] Candas Ercetin,Nuri Alper Sahbaz,Sami Acar,et al. Impact of photobiomodulation on T3/T4 ratio and quality of life in hashimoto thyroiditis[J]. Photobiomodul Photomed Laser Surg,2020,38(7):409-412. doi: 10.1089/photob.2019.4740 [3] Inês Henriques Vieira,Dírcea Rodrigues,Isabel Paiva. Vitamin D and autoimmune thyroid disease-cause,consequence,or a vicious cycle?[J]. Review Nutrients,2020,12(9):2791. doi: 10.3390/nu12092791 [4] Eva Petnehazy,Wolfgang Buchinger. Hashimoto thyroiditis,therapeutic options and extrathyroidal options-an up-to-date overview[J]. Wien Med Wochenschr,2020,170(1-2):26-34. doi: 10.1007/s10354-019-0691-1 [5] Sur Maria Luciaa,Gaga Remusb,Lazǎr Cǎlina,et al. Genetic and environmental factors in the pathophysiology of hashimoto's thyroiditis[J]. Pediatric Endocrinology Reviews,2020,17(4):343-348. [6] Xiaofei Wang,Wenli Cheng,Yu Ma,et al. Vitamin D receptor gene FokI but not TaqI,ApaI,BsmI polymorphism is associated with hashimoto's thyroiditis:A meta-analysis[J]. Meta-Analysis Sci Rep,2017,30(7):41540. [7] Xue Ren Gao, Yong-Guo Yu. Meta-Analysis of the Association between Vitamin D receptor polymorphisms and the risk of autoimmune thyroid disease[EB/OL]. [2018-03-22] [2021-04-25]. https://doi.org/10.1155/2018/2846943. [8] Bedia Guleryuz,Fulya Akin,Melek Tunc Ata,et al. Vitamin-D Receptor (VDR) gene polymorphisms (TaqI,FokI) in Turkish patients with hashimoto's thyroiditis:Relationship to the Levels of Vit-D and cytokines[J]. Endocr Metab Immune Disord Drug Targets,2016,16(2):131-139. doi: 10.2174/1871530316666160728092613 [9] Dr. S Mestiri,I Zaaber,I Nasr,et al. Implication of VDR Rs7975232 and FCGR2A Rs1801274 gene polymorphisms in the risk and the prognosis of autoimmune thyroid diseases in the tunisian population[J]. Balkan J Med Genet,2020,23(1):69-76. doi: 10.2478/bjmg-2020-0011 [10] Salvatore Giovinazzo,Teresa M Vicchio,Rosaria Certo,et al. Vitamin D receptor gene polymorphisms/haplotypes and serum 25(OH)D 3 levels in hashimoto's thyroiditis[J]. Endocrine,2017,55(2):599-606. doi: 10.1007/s12020-016-0942-5 [11] Adam Maciejewski, Michał J Kowalczyk, Waldemar Herman, et al. Vitamin D receptor gene polymorphisms and autoimmune thyroiditis: Are they associated with sisease occurrence and its features?[EB/OL]. [2019-08-21][2021-04-25]. https://doi.org/10.1155/2019/8197580. [12] 中华医学会内分泌学分会《中国甲状腺疾病诊治指南》编写. 中国甲状腺疾病诊治指南—甲状腺炎[J]. 中华内科杂志,2008,47(9):784-788. [13] 中华医学会骨质疏松和骨矿盐疾病分会. 维生素D及其类似物的临床应用共识[J]. 中华内分泌代谢杂志,2018,34(3):187-200. doi: 10.3760/cma.j.issn.1000-6699.2018.03.002 [14] 苏姗,张迪,王强梅,等. 维生素D与甲状腺疾病的相关性[J]. 中国临床药理学与治疗学,2020,25(1):94-100. doi: 10.12092/j.issn.1009-2501.2020.01.014 [15] Michael I Liontiris,Elias E Mazokopakis. A concise review of hashimoto thyroiditis (HT) and the importance of iodine,selenium,vitamin D and gluten on the autoimmunity and dietary managementof HT patients. Points that need more investigation[J]. Hell J Nucl Med,2017,20(1):51-56. [16] Dohee Kim. The role of vitamin D in thyroid diseases[J]. Review Int J Mol Sci,2017,18(9):1949. doi: 10.3390/ijms18091949 [17] Francesca Sassi, Cristina Tamone, Patrizia D’ Amelio. Vitamin D: Nutrient, hormone, and Immunomodulator. Nutrients. 2018, 10(11): 1656. [18] Ihnatowicz P,Drywień M,Wątor P,et al. The importance of nutritional factors and dietary management of hashimoto’ s thyroiditis[J]. Ann Agric Environ Med,2020,27(2):184-193. doi: 10.26444/aaem/112331 [19] Mario Štefanić,Stana Tokić. Serum 25-hydoxyvitamin D concentrations in relation to hashimoto's thyroiditis:A systematic review,meta-analysis and meta-regression of observational studies[J]. Meta-Analysis Eur J Nutr,2020,59(3):859-872. [20] Yaling Feng, Ting Qiu, Huijuan Chen, et al. Association of serum IL-21 and vitamin D concentrations in Chinese children with autoimmunethyroid disease[EB/OL]. [2020-08-28][2021-04-25]. https://doi.org/10.1016/j.cca.2020.04.030. [21] Chao G, Zhu Y, Fang L. Correlation between hashimoto’ s thyroiditis-related thyroid hormone levels and 25-HydroxyvitaminD[EB/OL]. [2020-02-14][2021-04-25]. https://doi.org/ 10.1155/2019/8197580. [22] Chahardoli R,Saboor-Yaraghi AA,Amouzegar A,et al. Can supplementation with vitamin D modify thyroid autoantibodies (Anti-TPO Ab,Anti-Tg Ab) and thyroid profile (T3,T4,TSH) in hashimoto's thyroiditis? A double blind,randomized clinical Trial[J]. Horm Metab Res,2019,51(5):296-301. doi: 10.1055/a-0856-1044 [23] Buthaina E Alathari,Aji A Sabta,Chinnappan A Kalpana,et al. Vitamin D pathway-related gene polymorphisms and their association with metabolic diseases:A literature review[J]. J Diabetes Metab Disord,2020,19(2):1701-1729. doi: 10.1007/s40200-020-00561-w [24] Chiara Mele,Marina Caputo,Alessandro Bisceglia,et al. Immunomodulatory effects of Vitamin D in thyroid diseases[J]. Review Nutrients,2020,12(5):1444. doi: 10.3390/nu12051444 [25] 李明. 维生素D受体基因、SOX4基因多态性与原发性骨质疏松症的相关性研究[D]. 太原: 右江民族医学院硕士学位论文, 2019. [26] Xia Ji,Jinbao Mao,Shuang Zhou. Rs739837 polymorphism in mir-885-3p binding site within 3′ -untranslated region of Vitamin D receptor is associated with a decreased risk of pressure ulcers[J]. Cell Physiol Biochem,2017,44(6):2129-2137. doi: 10.1159/000485952 [27] Jakob Skov,Jan Calissendorff,Daniel Eriksson Patrik Magnusson,et al. Limited genetic overlap between overt hashimoto’ s thyroiditis and graves’ disease in twins:A population-based study[J]. J Clin Endocrinol Metab,2021,106(4):1101-1110. doi: 10.1210/clinem/dgaa956 [28] Shin H R, Cho W K, Baek IC, et al. Polymorphisms of IRAK1 gene on x chromosome is associated with hashimoto thyroiditis in korean children. [EB/OL]. [2020-08-1][2021-04-25]. https://doi.org/10.1210/endocr/bqaa088. [29] Hasanbegovic E,Hasanbegovic S,Begic E. Hypothyroidism in pediatric population-bosnian and herzegovinian situation[J]. Med Arch,2017,71(1):62-65. [30] Soh S B,Aw T C. Laboratory testing in thyroid conditions-pitfalls and clinical utility[J]. Ann Lab Med,2019,39(1):3-14. doi: 10.3343/alm.2019.39.1.3 [31] Fang F, Chai Y, Wei H, et al. Vitamin D deficiency is associated with thyroid autoimmunity: Results from an epidemiological survey in Tianjin, China. [EB/OL]. [2021-03-23][2021-04-25]. https://doi.org/10.1007/s12020-021-02688-z. -
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