title: Ala45Thr variation in neuroD1 gene is associated with early-onset type 2 diabetes with or without diabetic pedigree in Chinese.
abstract: OBJECTIVE
  Based on onset-age stratified analysis may be useful to determine the association of NeuroD1-Ala45Thr variation with susceptibility to genetic heterogeneous type 2 diabetes mellitus (T2DM), we investigated the Ala45Thr variation in unrelated early-onset and late-onset T2DM with or without diabetic pedigree and unrelated non-diabetic control subjects in Chinese.
  
  
  METHODS
  175 early-onset and 194 late-onset type 2 diabetic patients were further divided into two subgroups according to with or without diabetic pedigree respectively. This NeuroD1-Ala45Thr variation were screened by PCR-direct sequencing in above 369 type 2 diabetic patients and 87 unrelated non-diabetic control subjects. We then compared the distribution of the Ala45Thr variation among the groups, searching for the predictive trends.
  
  
  RESULTS
  Frequencies of the variant (AA + GA genotype) in early-onset T2DM are obviously elevated, especially among diabetic pedigree subjects when compared to non-diabetic controls (p= 0.003) and late-onset T2DM subjects (p = 0.014). However, no significant differences were observed between late-onset T2DM with or without diabetic pedigree and non-diabetic control subjects.
  
  
  CONCLUSIONS
  Our results suggest that 1) the NeuroD1-Ala45Thr variation may itself have an important role in susceptibility to or be in disequilibrium with early-onset T2DM in Chinese; 2) the Ala45Thr may affect the onset pattern of T2DM, i.e., early-onset but not late-onset T2DM in Chinese; and 3) onset-age stratified analysis may be useful to determine the association of NeuroD1-Ala45Thr variation with susceptibility to genetic heterogeneous T2DM in Chinese.
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China. liulimei2001@hotmail.com
authors.forename: Limei
authors.initials: L
authors.lastname: Liu
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
authors.forename: Taishan
authors.initials: T
authors.lastname: Zheng
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Huijuan
authors.initials: H
authors.lastname: Lu
authors.forename: Kunsan
authors.initials: K
authors.lastname: Xiang
mesh_terms: D000328:Adult; D000368:Aged; D000409:Alanine; D019943:Amino Acid Substitution; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic; D013912:Threonine
chemical_list: D000409:Alanine; D051792:Basic Helix-Loop-Helix Proteins; D013912:Threonine; C093970:NEUROD1 protein, human