甲状腺激素转运蛋白基因（MCT8、MCT10 和 OATP1C1）单核苷酸多态性与循环甲状腺激素的关系。
Associations between single nucleotide polymorphisms in thyroid hormone transporter genes (MCT8, MCT10 and OATP1C1) and circulating thyroid hormones.
机构信息
Department of Endocrinology, Ghent University Hospital, Belgium.
出版信息
Clin Chim Acta. 2013 Oct 21;425:227-32. doi: 10.1016/j.cca.2013.08.017. Epub 2013 Aug 24.
BACKGROUND
Thyroid hormone (TH) action takes place intracellularly; therefore, transport across the plasma membrane by specific TH transporters, such as MCT8, MCT10 and OATP1C1, is necessary. Several single nucleotide polymorphisms (SNPs) in these genes were reported to be associated with TH concentrations; however, results have been inconsistent.
METHODS
Six SNPs in TH transporter genes (rs5937843-G/T and rs6647476-T/C in MCT8, rs14399-C/A in MCT10, rs10444412-C/T, rs10770704-C/T and rs36010656-C/A in OATP1C1) were genotyped in 2 cohorts; one consisting of 2416 men and women aged 35-55 yrs (Asklepios), and the other of 941 men aged 25-45 yrs (Siblos), using KASPar technology. TSH, FT3, FT4 and total T3 were determined by immuno-electrochemiluminescence in both cohorts; in the second cohort additional determination of total T4 by electrochemiluminescence and of reverse T3 (rT3) and thyroid binding globulin (TBG) by radioimmunoassays was performed.
RESULTS
The first SNP in MCT8 (rs5937843-G/T) was inversely associated with FT4 concentrations in men but not in women. In Siblos, this SNP showed also negative associations with TT4 and rT3; in men from Asklepios a trend for positive association with TSH was observed. The second SNP in MCT8 (rs6647476-T/C) was negatively associated with FT3 levels in men from the Siblos and the Asklepios cohort. In addition, an inverse association with TT3 levels in men from the Siblos was observed. Rs36010656 (C/A) in OATP1C1 was not in Hardy-Weinberg equilibrium and therefore excluded from further analyses. The other 2 SNPs in OATP1C1 (rs10444412-C/T and rs10770704-C/T) and the SNP in MCT10 (rs14399-C/A) were not related to TH levels in either cohort.
CONCLUSION
Two SNPs in MCT8 were related to circulating thyroid hormone levels in men but not in women: the rs5937843 polymorphism (G/T) was inversely associated with FT4 levels and the rs6647476 (T/C) polymorphism related negatively to circulating FT3.
背景
甲状腺激素（TH）的作用发生在细胞内；因此，特定的 TH 转运蛋白，如 MCT8、MCT10 和 OATP1C1，的跨膜转运是必要的。这些基因中的几个单核苷酸多态性（SNP）被报道与 TH 浓度相关；然而，结果并不一致。
方法
在两个队列中对 TH 转运蛋白基因中的 6 个 SNP（MCT8 中的 rs5937843-G/T 和 rs6647476-T/C、MCT10 中的 rs14399-C/A、OATP1C1 中的 rs10444412-C/T、rs10770704-C/T 和 rs36010656-C/A）进行了基因分型；一个队列由 2416 名 35-55 岁的男性和女性（Asklepios）组成，另一个队列由 941 名 25-45 岁的男性（Siblos）组成，使用 KASPar 技术。在两个队列中均通过免疫电化学发光法测定 TSH、FT3、FT4 和总 T3；在第二个队列中，还通过电化学发光法测定总 T4，通过放射免疫法测定反式 T3（rT3）和甲状腺结合球蛋白（TBG）。
结果
MCT8 中的第一个 SNP（rs5937843-G/T）与男性的 FT4 浓度呈负相关，但与女性无关。在 Siblos 中，该 SNP 与 TT4 和 rT3 也呈负相关；在 Asklepios 队列中的男性中，观察到与 TSH 呈正相关的趋势。MCT8 中的第二个 SNP（rs6647476-T/C）与 Siblos 和 Asklepios 队列中男性的 FT3 水平呈负相关。此外，还观察到与 Siblos 男性的 TT3 水平呈负相关。OATP1C1 中的 rs36010656（C/A）与 Hardy-Weinberg 平衡不一致，因此被排除在进一步分析之外。OATP1C1 中的另外 2 个 SNP（rs10444412-C/T 和 rs10770704-C/T）和 MCT10 中的 SNP（rs14399-C/A）与两个队列中的 TH 水平均无关。
结论
MCT8 中的两个 SNP 与男性的循环甲状腺激素水平有关，但与女性无关：rs5937843 多态性（G/T）与 FT4 水平呈负相关，rs6647476（T/C）多态性与循环 FT3 呈负相关。
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