Is Puberty an Accelerator of Type 1 Diabetes in IL6-174CC Females?

• Published in: Diabetes (New York, N.Y.) Vol. 54; no. 4; pp. 1245 - 1248
• Main Authors: GILLESPIE, Kathleen M, NOLSØE, Runa, BETIN, Virginie M, KRISTIANSEN, Ole P, BINGLEY, Polly J, MANDRUP-POULSEN, Thomas, GALE, Edwin A. M
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.04.2005
• Subjects: Adolescent; Age; Age of Onset; Biological and medical sciences; Child; Cohort Studies; Cytokines; Diabetes; Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Estrogens; Estrogens - physiology; Evaluation; Female; Genes; Genetic aspects; Genotype; Genotype & phenotype; Girls; Humans; Hypotheses; Interleukin-6; Interleukin-6 - genetics; Male; Males; Medical sciences; Medicin och hälsovetenskap; Polymorphism; Polymorphism, Single Nucleotide; Puberty; Puberty - physiology; Sex Factors; Type 1 diabetes; United States; United Kingdom > UK; Endocrinopathy; Immunopathology; Puberty; Autoimmune disease; Female; Type 1 diabetes
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.54.4.1245

Is Puberty an Accelerator of Type 1 Diabetes in IL6-174CC Females? Kathleen M. Gillespie 1 , Runa Nolsøe 2 , Virginie M. Betin 1 , Ole P. Kristiansen 2 , Polly J. Bingley 1 , Thomas Mandrup-Poulsen 2 3 and Edwin A.M. Gale 1 1 Department of Diabetes and Metabolism, Division of Medicine, University of Bristol, U.K 2 Steno Diabetes Center, Gentofte, Denmark 3 Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden Address correspondence and reprint requests to Dr. K.M. Gillespie, Medical School Unit, Southmead Hospital, Bristol BS10 5NB, U.K. E-mail: k.m.gillespie{at}bristol.ac.uk 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. BOX, Bart’s Oxford IL, interleukin NF, nuclear factor SNP, single nucleotide polymorphism Footnotes T.M.-P. is employed by, holds stock in, and has received grant/research support from Novo Nordisk. Accepted December 16, 2004. Received October 7, 2004. DIABETES