Khoshi Amirhosein, Sirghani Alireza, Ghazisaeedi Mehran, Mahmudabadi Ali Zarei, Azimian Amir
Department of Medical Biotechnology and Molecular Sciences, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, P.C.: 9417694735, Iran.
Department of Biochemistry, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Hormones (Athens). 2017 Jan;16(1):75-83. doi: 10.14310/horm.2002.1721.
Subclinical hypothyroidism (SCH) is defined as high levels of TSH in the presence of normal levels of serum FT4. Since thyroid peroxidase (TPO) plays a key role in thyroid hormone synthesis, variations in the TPO gene can change the enzyme structure and result in the production of anti-TPO antibodies. The aim of this study was to examine the relationship between the Asn698Thr (A2095C) and Thr725Pro (A2173C) polymorphisms of the TPO gene and anti-TPO levels in patients with SCH.
In this study, 150 individuals (75 cases and 75 controls), aged 19-75 years, were selected randomly by a clinician. The thyroid function tests included were FT3, FT4, TSH and anti-TPO antibodies using ELISA. The TPO gene polymorphisms were examined by PCR-RFLP.
Anti-TPO levels in the experimental group was significantly increased (P=0.020). The A2095C genotype frequency in the experimental and control groups were 37.3% vs 34.7% for the AA healthy genotype, 20% vs 46.7% for AC and 42.7% vs 18.6% for CC, respectively (P=0.001). The A2173C genotype frequency in the experimental and control groups were 22.6% vs 68% for healthy AA, 40% vs 25.3% for AC and 37.4% vs 6.7% for CC, respectively (P <0.001). The increased anti-TPO antibodies were significantly associated with the A2173C polymorphism (P=0.035). The findings showed that the chance (odds ratio) of developing subclinical hypothyroidism in individuals who had C alleles was 1.5 and 5.6-fold higher than in individuals without these alleles in the A2095C and A2173C regions, respectively.
Determination of anti-TPO antibody levels and exon 12 TPO gene polymorphisms in patients with SCH can be helpful for prediction of overt hypothyroidism.
亚临床甲状腺功能减退症（SCH）的定义是血清游离甲状腺素（FT4）水平正常但促甲状腺激素（TSH）水平升高。由于甲状腺过氧化物酶（TPO）在甲状腺激素合成中起关键作用，TPO基因的变异可改变酶的结构并导致抗甲状腺过氧化物酶（anti-TPO）抗体的产生。本研究旨在探讨TPO基因Asn698Thr（A2095C）和Thr725Pro（A2173C）多态性与SCH患者anti-TPO水平之间的关系。
本研究中，由一名临床医生随机选取了150名年龄在19至75岁之间的个体（75例患者和75例对照）。所进行的甲状腺功能检查包括使用酶联免疫吸附测定（ELISA）法检测FT3、FT4、TSH和anti-TPO抗体。通过聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）检测TPO基因多态性。
实验组的anti-TPO水平显著升高（P=0.020）。实验组和对照组中，AA健康基因型的A2095C基因型频率分别为37.3%和34.7%，AC基因型分别为20%和$46.7%$，CC基因型分别为42.7%和18.6%（P=0.001）。实验组和对照组中，健康AA基因型的A2173C基因型频率分别为22.6%和68%，AC基因型分别为40%和25.3%，CC基因型分别为37.4%和6.7%（P<0.001）。anti-TPO抗体升高与A$2173$C多态性显著相关（P=0.035）。研究结果表明，在A2095C和A2173C区域中，携带C等位基因的个体发生亚临床甲状腺功能减退症的几率分别比不携带这些等位基因的个体高1.5倍和5.6倍。
检测SCH患者的anti-TPO抗体水平和TPO基因第12外显子多态性有助于预测显性甲状腺功能减退症。
