title: X-chromosome gene dosage and the risk of diabetes in Turner syndrome.
abstract: BACKGROUND
  Turner syndrome (TS) is caused by the absence or fragmentation of the second sex chromosome. An increased risk of diabetes mellitus (DM) has consistently been noted, but the specific phenotype and genetic etiology of this trait are unknown.
  
  
  METHODS
  In a prospective study, we examined the prevalence of DM in adult participants in an intramural National Institutes of Health (NIH) TS study. Results were analyzed with respect to karyotype, age, body mass index (BMI), and autoimmune indices. Insulin sensitivity and secretion were compared in age- and BMI-matched euglycemic women with TS and healthy female controls. We compared gene expression profiles in lymphocytes from differentially affected TS groups.
  
  
  RESULTS
  Type 2 DM was present in 56 of 224 (25%) of the women with TS; type 1 DM was found in only one woman (<0.5%). DM was more prevalent among women with an isoXq chromosome compared to X monosomy (40.0 vs. 17.3%; P = 0.004). Euglycemic women with TS (n = 72; age, 33 +/- 12 yr; BMI, 23 +/- 3 kg/m(2)) had significantly higher glycemic and lower insulin responses to OGTT, with insulin sensitivity similar to controls. Gene expression profiles comparing 46,X,i(X)q vs. 45,X groups showed a significant increase in Xq transcripts and in potentially diabetogenic autosomal transcripts in the isoXq group.
  
  
  CONCLUSIONS
  Type 2 DM associated with deficient insulin release is significantly increased among women with monosomy for the X-chromosome but is increased even more among women with monosomy for Xp coupled with trisomy for Xq. These data suggest that haploinsufficiency for unknown Xp genes increases risk for DM and that excess dosage of Xq genes compounds the risk.
authors: National Institute of Child Health and Human Development, Clinical Research Center, 10 Center Drive, Bethesda, Maryland 20892, USA. bakalov@mail.nih.gov
authors: Vladimir K
authors: VK
authors: Bakalov
authors: Clara
authors: C
authors: Cheng
authors: Jian
authors: J
authors: Zhou
authors: Carolyn A
authors: CA
authors: Bondy
mesh_terms: D000328:Adult; D000368:Aged; D015551:Autoimmunity; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D050172:Genes, X-Linked; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D015995:Prevalence; D012306:Risk; D014424:Turner Syndrome / Q000150:complications / Q000235:genetics* / Q000378:metabolism
chemical_list: D005947:Glucose