title: Evidence for the association of the SLC22A4 and SLC22A5 genes with type 1 diabetes: a case control study.
abstract: BACKGROUND
  Type 1 diabetes (T1D) is a chronic, autoimmune and multifactorial disease characterized by abnormal metabolism of carbohydrate and fat. Diminished carnitine plasma levels have been previously reported in T1D patients and carnitine increases the sensitivity of the cells to insulin. Polymorphisms in the carnitine transporters, encoded by the SLC22A4 and SLC22A5 genes, have been involved in susceptibility to two other autoimmune diseases, rheumatoid arthritis and Crohn's disease. For these reasons, we investigated for the first time the association with T1D of six single nucleotide polymorphisms (SNPs) mapping to these candidate genes: slc2F2, slc2F11, T306I, L503F, OCTN2-promoter and OCTN2-intron.
  
  
  METHODS
  A case-control study was performed in the Spanish population with 295 T1D patients and 508 healthy control subjects. Maximum-likelihood haplotype frequencies were estimated by applying the Expectation-Maximization (EM) algorithm implemented by the Arlequin software.
  
  
  RESULTS
  When independently analyzed, one of the tested polymorphisms in the SLC22A4 gene at 1672 showed significant association with T1D in our Spanish cohort. The overall comparison of the inferred haplotypes was significantly different between patients and controls (chi2 = 10.43; p = 0.034) with one of the haplotypes showing a protective effect for T1D (rs3792876/rs1050152/rs2631367/rs274559, CCGA: OR = 0.62 (0.41-0.93); p = 0.02).
  
  
  CONCLUSIONS
  The haplotype distribution in the carnitine transporter locus seems to be significantly different between T1D patients and controls; however, additional studies in independent populations would allow to confirm the role of these genes in T1D risk.
authors.affiliation: Immunology Department, Hospital Universitario San Carlos, Madrid, Spain. jlsanti@hotmail.com
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Santiago
authors.forename: Alfonso
authors.initials: A
authors.lastname: Martínez
authors.forename: Hermenegildo
authors.initials: H
authors.lastname: de la Calle
authors.forename: Miguel
authors.initials: M
authors.lastname: Fernández-Arquero
authors.forename: M Angeles
authors.initials: MA
authors.lastname: Figueredo
authors.forename: Emilio G
authors.initials: EG
authors.lastname: de la Concha
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002895:Chromosomes, Human, Pair 5; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000074058:Solute Carrier Family 22 Member 5; D013030:Spain; D027981:Symporters
chemical_list: D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters