Associations between single nucleotide polymorphisms in thyroid hormone transporter genes (MCT8, MCT10 and OATP1C1) and circulating thyroid hormones

• Published in: Clinica chimica acta Vol. 425; pp. 227 - 232
• Main Authors: Roef, Greet L., Rietzschel, Ernst R., De Meyer, Tim, Bekaert, Sofie, De Buyzere, Marc L., Van daele, Caroline, Toye, Kaatje, Kaufman, Jean-Marc, Taes, Youri E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 21-10-2013
• Subjects: Adult; Amino Acid Transport Systems, Neutral - genetics; Amino Acid Transport Systems, Neutral - metabolism; Biological Transport; Cell Membrane - metabolism; Cross-Sectional Studies; Female; Gene Expression; Humans; Male; Middle Aged; Monocarboxylate transporter 8 and 10; Monocarboxylic Acid Transporters - genetics; Monocarboxylic Acid Transporters - metabolism; Organic Anion Transporters - genetics; Organic Anion Transporters - metabolism; Organic anion transporting polypeptide 1C1; Polymorphism, Single Nucleotide; Reference Values; Sex Factors; Single nucleotide polymorphism (SNP); Thyroid Gland - metabolism; Thyroid hormone concentrations; Thyroid hormone transporters; Thyrotropin - blood; Thyrotropin - genetics; Thyroxine - blood; Thyroxine - genetics; Triiodothyronine - blood; Triiodothyronine - genetics; TSH; TSH; Thyroid hormone concentrations; Single nucleotide polymorphism (SNP); Monocarboxylate transporter 8 and 10; Thyroid hormone transporters; Organic anion transporting polypeptide 1C1
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2013.08.017

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.
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 35–55yrs (Asklepios), and the other of 941 men aged 25–45yrs (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.
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.
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.
•6 SNPs in 3 different TH transporters (MCT8, MCT10, OATP1C1)•Genotyped in 2 cohorts, one consisting of 2416 men and women, and the second of 941 men•SNP 1 in MCT8 (rs5937843) inversely associated with FT4 concentrations in men•SNP 2 in MCT8 (rs6647476) negatively associated with FT3 levels in men•SNPs in MCT10 and OATP1C1 were not related to TH levels.