Abstract:

Objective　To explore the clinical value of uridine 5′-diphospho-glucuronosyltransferase 1-1 (UGT1A1) gene polymorphism in pregnant women with hypothyroidism in Bao'an area. Methods　One hundred women with hypothyroidism during pregnancy treated at Shiyan People's Hospital from January 2021 to February 2022 were selected as an observation group, and 100 healthy women with normal thyroid function taking property inspection during the same period were selected as a control group. The fasting venous blood of all the subjects was taken for RNA extraction and sequencing. The observation group were routinely treated with levothyroxine tablets for 4 weeks. The serum levels of thyroid stimulating hormone (TSH) and thyroid peroxidase antibody (TPOAb) were detected. The χ², paired t, or F tests were applied. Results　In the observation group, there were 73 cases of UGT1A1*6 wild type, 23 cases of heterozygous mutation type (G/A), 4 cases of homozygous mutation type (A/A), 70 cases of UGT1A1*28 wild type, 27 cases of G/A type, and 3 cases of A/A type; in the control group, there were 69 cases of UGT1A1*6 wild type, 26 cases of G/A type, 5 cases of A/A type, 72 cases of UGT1A1*28 wild type, 26 cases of G/A type, and 2 cases of A/A type; there were no statistical differences in UGT1A1*6 and UGT1A1*28 gene polymorphisms between the observation group and the control group (both P>0.05). Before the treatment, there were no statistical differences in TSH and TPOAb levels between the patients with different UGT1A1*6 and UGT1A1*28 genotypes (all P>0.05); after the treatment, the TSH and TPOAb levels of the patients of UGT1A1*6 and UGT1A1*28 wild types were the highest, those of the patients of UGT1A1*6 G/A type were the second, and the TSH level of the patients of UGT1A1*6 A/A type was the lowest, with statistical differences (all P<0.05). Conclusions　The UGT1A1 gene polymorphism in women with hypothyroidism during pregnancy is similar to that in healthy pregnant women. The levels of TSH and TPOAb in patients with UGT1A1*6 and UGT1A1*28 homozygous mutant hypothyroidisms during pregnancy after clinical treatment are significantly reduced. Clinically, it should consider to give an appropriate dose of drug treatment according to the UGT1A1 genotypes.

Key words: UGT1A1, Gene polymorphism, Pregnant women, Hypothyroidism, Clinical value

摘要： 目的　探究尿苷二磷酸葡萄糖醛酸转移酶1A1（UGT1A1）基因多态性对宝安地区女性妊娠期甲状腺功能减退的临床价值。方法　以2021年1月至2022年2月就诊于深圳市宝安区石岩人民医院妊娠期甲状腺功能减退的女性100例为观察组，同时选取同期产检甲状腺功能正常的健康女性100例为对照组。取所有研究对象的空腹静脉血，进行RNA提取和测序，给予观察组左甲状腺素片常规治疗4周后，检测血清促甲状腺激素（thyroid stimulating hormone，TSH）和甲状腺过氧化物酶抗体（thyroid peroxidase antibody，TPOAb）水平。采用χ²检验、配对t检验或F检验。结果　观察组中UGT1A1*6野生型73例，杂合突变（G/A）型23例，纯合突变（A/A）型4例，UGT1A1*28野生型70例，G/A型27例，A/A型3例；对照组中UGT1A1*6野生型69例，G/A型26例，A/A型5例，UGT1A1*28野生型72例，G/A型26例，A/A型2例；UGT1A1*6和UGT1A1*28基因多态性在观察组和对照组中差异均无统计学意义（均P>0.05）。妊娠期甲状腺功能减退患者治疗前，不同UGT1A1*6和UGT1A1*28基因型患者的TSH和TPOAb水平差异均无统计学意义（均P>0.05）；治疗后，UGT1A1*6和UGT1A1*28野生型患者的TSH和TPOAb水平最高，UGT1A1*6 G/A型患者次之，UGT1A1*6 A/A型患者的TSH水平最低，差异均有统计学意义（均P<0.05）。结论　妊娠期甲状腺功能减退女性的UGT1A1基因多态性与健康妊娠女性类似，UGT1A1*6和UGT1A1*28纯合突变型妊娠期甲状腺功能减退患者临床治疗后TSH和TPOAb水平显著降低，临床上应考虑结合UGT1A1基因型给予适合剂量的药物治疗。

关键词: UGT1A1, 基因多态性, 妊娠女性, 甲状腺功能减退, 临床价值