title: Associations between single nucleotide polymorphisms in thyroid hormone transporter genes (MCT8, MCT10 and OATP1C1) and circulating thyroid hormones.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Endocrinology, Ghent University Hospital, Belgium. Electronic address: greet.roef@ugent.be.
authors: Greet L
authors: GL
authors: Roef
authors: Ernst R
authors: ER
authors: Rietzschel
authors: Tim
authors: T
authors: De Meyer
authors: Sofie
authors: S
authors: Bekaert
authors: Marc L
authors: ML
authors: De Buyzere
authors: Caroline
authors: C
authors: Van daele
authors: Kaatje
authors: K
authors: Toye
authors: Jean-Marc
authors: JM
authors: Kaufman
authors: Youri E
authors: YE
authors: Taes
mesh_terms: D000328:Adult; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics* / Q000378:metabolism; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000235:genetics* / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D012737:Sex Factors; D027981:Symporters; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood / Q000235:genetics; D013974:Thyroxine / Q000097:blood / Q000235:genetics; D014284:Triiodothyronine / Q000097:blood / Q000235:genetics
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D027501:Monocarboxylic Acid Transporters; D027361:Organic Anion Transporters; C498964:SLC16A10 protein, human; C090735:SLC16A2 protein, human; C473187:SLCO1C1 protein, human; D027981:Symporters; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine
keywords: Monocarboxylate transporter 8 and 10; Organic anion transporting polypeptide 1C1; Single nucleotide polymorphism (SNP); TSH; Thyroid hormone concentrations; Thyroid hormone transporters