title: Is puberty an accelerator of type 1 diabetes in IL6-174CC females?
abstract: The pubertal peak in onset of type 1 diabetes occurs earlier in girls than boys. We postulated that this sex difference might be mediated in part by estrogen or by genes regulated by estrogen, such as the interleukin-6 (IL6) gene. Previous studies concerning the role of an estrogen-sensitive single nucleotide polymorphism (SNP) in the IL6 promoter in type 1 diabetes have proved contradictory. We therefore selected a large, genetically homogenous population-based cohort, analyzed by age at onset and sex, to test the hypothesis that the IL6-174G>C SNP affects age at onset of type 1 diabetes in females but not in males. We found that the IL6-174CC genotype was significantly less frequent in females diagnosed after than in those diagnosed before the age of 10 years (19 vs. 13%, P = 0.016). No genotype difference was observed in males stratified for age at onset. Among children diagnosed after age 10, the median age of onset was 11.9 years (intraquartile range 10.7-14.6) in 34 girls homozygous for IL6-174C compared with 13.2 years (11.6-15.4) in 229 girls with other genotypes and 13.5 years (12.0-15.6) in 339 males with any IL6-174 genotype (P = 0.012). These data support the hypothesis that pubertal changes may contribute to accelerated onset of type 1 diabetes in genetically susceptible females. This phenomenon may be orchestrated by the action of estrogen on the IL6 promoter.
authors.affiliation: Department of Diabetes and Metabolism, Division of Medicine, University of Bristol, UK. k.m.gillespie@bristol.ac.uk <k.m.gillespie@bristol.ac.uk>
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gillespie
authors.forename: Runa
authors.initials: R
authors.lastname: Nolsøe
authors.forename: Virginie M
authors.initials: VM
authors.lastname: Betin
authors.forename: Ole P
authors.initials: OP
authors.lastname: Kristiansen
authors.forename: Polly J
authors.initials: PJ
authors.lastname: Bingley
authors.forename: Thomas
authors.initials: T
authors.lastname: Mandrup-Poulsen
authors.forename: Edwin A M
authors.initials: EA
authors.lastname: Gale
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D004967:Estrogens / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011627:Puberty / Q000502:physiology*; D012737:Sex Factors
chemical_list: D004967:Estrogens; D015850:Interleukin-6