title: The association of cytotoxic T-lymphocyte antigen-4 + 49A/G and CT60 polymorphisms with type 1 diabetes and latent autoimmune diabetes in Chinese adults.
abstract: OBJECTIVE
  The aim of this study was to investigate the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) + 49A/G and CT60 polymorphisms with latent autoimmune diabetes in adults (LADA) and the genetic differences between LADA, type 1 diabetes (T1DM), and type 2 diabetes (T2DM) in a Chinese population.
  
  
  METHODS
  A total of 231 LADA, 402 T1DM, and 330 T2DM patients as well as 482 nondiabetic controls were recruited in the study.
  
  
  METHODS
  CTLA-4 + 49A/G and CT60 polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The level of glutamic acid decarboxylase antibodies (GADAs) was detected by a radioligand binding assay.
  
  
  RESULTS
  The CTLA-4 + 49A/G risk genotype GG was most frequent in T1DM patients (45.3%), followed by LADA patients (44.2%) and T2DM patients (38.8%). Significantly higher frequencies of the risk genotype GG were observed in the T1DM (OR = 1.532, 95% CI 1.168-2.010, P = 0.002) and LADA patients (OR = 1.464, 95% CI 1.063-2.017, P = 0.019). The frequencies of the CTLA-4 CT60 risk genotype GG were 65.2, 61.9, 58.5, and 56.4% in the T1DM, LADA, T2DM, and control groups, respectively. The CTLA-4 CT60 GG risk genotypes were only associated with T1DM (OR = 1.445, 95% CI 1.1-1.898, P = 0.008). Compared with controls, patients having a high titer of GADA (GADA ≥ 180 IU/ml) had higher frequencies of the GG risk genotype of CTLA-4 + 49 A/G (49.4% vs. 35.1% OR = 1.807, 95% CI 1.125-2.903, P = 0.014), but there was no difference between patients having a low titer of GADA and controls.
  
  
  CONCLUSIONS
  The CTLA-4 + 49 A/G polymorphism confers genetic susceptibility to LADA and T1DM, while the CTLA-4 CT60 polymorphism is only associated with T1DM in Chinese population. The CTLA-4 + 49 A/G genotype distribution in LADA is associated with the GADA level.
authors.affiliation: Department of Endocrinology, Diabetes Center, Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.|Department of Endorcrinology, The Third Xiangya Hospital, Central South University, Changsha, 410007, Hunan, People's Republic of China.
authors.forename: P
authors.initials: P
authors.lastname: Jin
authors.affiliation: Department of Endocrinology, Diabetes Center, Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: B
authors.initials: B
authors.lastname: Xiang
authors.affiliation: Department of Endocrinology, Diabetes Center, Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: G
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Endocrinology, Diabetes Center, Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. dongge1899@vip.sina.com.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human
keywords: Autoantibodies; Cytotoxic T-lymphocyte antigen-4; Glutamic acid decarboxylase; Latent autoimmune diabetes in adults; Polymorphism; Type 1 diabetes