title: Familial early-onset type 2 diabetes in Chinese patients: obesity and genetics have more significant roles than autoimmunity.
abstract: OBJECTIVE
  We examined the prevalence of different forms of diabetes in Hong Kong Chinese patients with familial early-onset type 2 diabetes and compared their clinical features with patients with familial late-onset type 2 diabetes.
  
  
  METHODS
  A total of 145 young patients with early-onset diabetes (age and age at diagnosis < or = 40 years) and a family history of diabetes were studied. They were screened for mutations in the genes encoding glucokinase, hepatocyte nuclear factor (HNF)-4alpha, and HNF-1alpha. The mitochondrial DNA A-->G at nucleotide 3243 (mt3243) and amyLin S20G mutations were studied, and antibodies to GAD (anti-GADs) were also examined.
  
  
  RESULTS
  The prevalence of putative diabetogenic gene mutations and autoimmune markers were 4% for glucokinase, 0% for HNF-4alpha, 5% for HNF-1alpha, 3% for mt3243, 2% for amylin 520G, and 4% for anti-GAD. Compared with late-onset patients, the patients with early-onset diabetes had a higher prevalence of a parental history of diabetes and were generally more obese. When classified by obesity indexes (BMI and waist circumference), the obese patients, especially those with early-onset diabetes, had a clustering of cardiovascular risk factors and increased rates of retinopathy and albuminuria. CONCLUSIONS; Genetic factors (up to 14%) and obesity (55%) play more significant roles than autoimmunity (4%) in familial type 2 diabetes in young Chinese patients. The significance of obesity-related genes and other gene-gene and gene-environment interactions in these young patients remains to be determined.
authors.affiliation: Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, SAR. maggieng@cuhk.edu.hk
authors.forename: M C
authors.initials: MC
authors.lastname: Ng
authors.forename: S C
authors.initials: SC
authors.lastname: Lee
authors.forename: G T
authors.initials: GT
authors.lastname: Ko
authors.forename: J K
authors.initials: JK
authors.lastname: Li
authors.forename: W Y
authors.initials: WY
authors.lastname: So
authors.forename: Y
authors.initials: Y
authors.lastname: Hashim
authors.forename: A H
authors.initials: AH
authors.lastname: Barnett
authors.forename: I R
authors.initials: IR
authors.lastname: Mackay
authors.forename: J A
authors.initials: JA
authors.lastname: Critchley
authors.forename: C S
authors.initials: CS
authors.lastname: Cockram
authors.forename: J C
authors.initials: JC
authors.lastname: Chan
mesh_terms: D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D000682:Amyloid / Q000235:genetics; D044466:Asian People / Q000235:genetics; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004272:DNA, Mitochondrial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003920:Diabetes Mellitus / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D005091:Exons; D005260:Female; D005941:Glucokinase / Q000235:genetics; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051557:Hepatocyte Nuclear Factor 4; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins; D009765:Obesity; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D012042:Registries; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000682:Amyloid; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D058228:Islet Amyloid Polypeptide; C403128:MLX protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D005941:Glucokinase