title: Polymorphisms in chromosome region 12q13 and their influence on age at onset of type 1 diabetes.
abstract: OBJECTIVE
  A complex region covering numerous genes in 12q13 was first associated with type 1 diabetes in the Wellcome Trust Case-Control Consortium (WTCCC) study. Two studies performed in a white population have tested the association of polymorphisms within this region with age at onset of the disease, with seemingly contradictory results. We aimed at replicating three of the strongest signals in a group of patients with early and late disease onset.
  
  
  METHODS
  Polymorphisms rs773107, rs2292239 and rs10876864 were genotyped in 444 type 1 diabetic Spanish participants (age at onset 0-65 years) and 861 controls. The influence of single nucleotide polymorphisms (SNPs) on age at onset was tested through stratified and continuous analyses.
  
  
  RESULTS
  rs773107 and rs2292239 were significantly associated with the disease, while rs10876864 showed a trend towards statistical significance in the whole population analyses. Comparison of early-onset patients to controls was significant for the three polymorphisms (allelic p < 0.006). Late-onset patients and controls did not reveal statistical differences. Analysis of age at onset in both rs773107 and rs2292239 showed differences between genotypes (p ≤ 0.002), alleles (p ≤ 0.013) and homozygotes for the risk genotype (p ≤ 4 × 10(-4)). Polymorphism rs10876864 showed trends towards statistical significance in the allelic frequencies (p = 0.051) and homozygotes for the risk genotype (p = 0.056). Subjects with risk genotypes had a disease onset between 2 and 5 years earlier than carriers of protective alleles.
  
  
  CONCLUSIONS
  We replicate two of the previously studied associations in a Spanish population and find new evidence of the influence of the 12q13 region on age at onset of type 1 diabetes.
authors.affiliation: Immunology Department, Hospital Clínico San Carlos, Instituto de Investigacíon Sanitaria San Carlos (IdISSC), Martín Lagos s/n, 28040 Madrid, Spain. lauraep80@yahoo.es
authors.forename: L
authors.initials: L
authors.lastname: Espino-Paisan
authors.forename: H
authors.initials: H
authors.lastname: de la Calle
authors.forename: M
authors.initials: M
authors.lastname: Fernández-Arquero
authors.forename: M A
authors.initials: MA
authors.lastname: Figueredo
authors.forename: E G
authors.initials: EG
authors.lastname: de la Concha
authors.forename: E
authors.initials: E
authors.lastname: Urcelay
authors.forename: J L
authors.initials: JL
authors.lastname: Santiago
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D055815:Young Adult