title: Prevalence and functional analysis of the S107P polymorphism (rs6647476) of the monocarboxylate transporter 8 (SLC16A2) gene in the male population of north-west Spain (Galicia).
abstract: OBJECTIVE
  Mutations in SLC16A2, the gene encoding the thyroid hormone (TH)-specific transporter monocarboxylate transporter 8 (MCT8), result in a thyroid phenotype and severe mental retardation caused by neuronal TH deficiency. These mutational effects raise the question of whether polymorphic variation in SLC16A2 may also be associated with differences in serum levels of TH and/or TSH.
  
  
  METHODS
  This is the first major study of the frequency of the SLC16A2 rs6647476 single nucleotide polymorphism (SNP) (amino acid change Ser107Pro). We also studied the relationships of SLC16A2 genetic variants with serum levels of TSH, T4 and T3, with their mRNA expression and with expression of the TH-responsive genes ZAKI-4 and BTEB in white blood cells. Experiments in cultured fibroblasts were carried out to ascertain the dynamics of the T3 response.
  
  
  METHODS
  A total of 276 men were studied. Genotyping of the S107P SNP was carried out using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP); serum hormone levels were determined by chemiluminescence; expression of mRNA was quantified by real-time PCR.
  
  
  RESULTS
  The SLC16A2 S107P SNP was found in 36% of Galician males. With the present sample size we did not find any association of this polymorphism with variability in serum levels of TSH, free T4 (fT4) or fT3, or with basal expression of mRNA for SLC16A2 or the two TH-responsive genes ZAKI-4 and BTEB, either in white blood cells or in cultured human fibroblasts from either Ser107 or Pro107 genotypes under T3 stimulation.
  
  
  CONCLUSIONS
  The S107P change in MCT8 is frequent in the male population in Galicia. In the population studied in this report an association with a thyroid phenotype was not demonstrated, even though the S107P SNP causes an important amino acid change.
authors: Departamento de Medicina, Unidade de Enfermedades Tiroideas e Metabólicas, Universidad de Santiago de Compostela, Spain.
authors: Ramón
authors: R
authors: Lago-Lestón
authors: María-José
authors: MJ
authors: Iglesias
authors: Esther
authors: E
authors: San-José
authors: Carlos
authors: C
authors: Areal
authors: Adolfo
authors: A
authors: Eiras
authors: David
authors: D
authors: Araújo-Vilar
authors: Joaquín
authors: J
authors: Lado-Abeal
authors: Lourdes
authors: L
authors: Domínguez-Gerpe
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005787:Gene Frequency / Q000235:genetics*; D005838:Genotype; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D027501:Monocarboxylic Acid Transporters / Q000235:genetics* / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013030:Spain; D027981:Symporters; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D044465:White People / Q000208:ethnology* / Q000235:genetics*; D055815:Young Adult
chemical_list: C489676:KLF9 protein, human; D051741:Kruppel-Like Transcription Factors; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; C100360:RCAN2 protein, human; D012333:RNA, Messenger; C090735:SLC16A2 protein, human; D027981:Symporters; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine