title: Insulin gene VNTR polymorphisms -2221MspI and -23HphI are associated with type 1 diabetes and latent autoimmune diabetes in adults: a meta-analysis.
abstract: OBJECTIVE
  A variable number of tandem repeat (VNTRs) region in the insulin gene (INS) possibly influences the progression of type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA). However, effects of INS VNTR polymorphisms in these contexts remain inconclusive.
  
  
  METHODS
  We performed a systematic review of work on the INS VNTR -2221MspI and -23HphI polymorphisms to estimate the overall effects thereof on disease susceptibility; we included 17,498 T1D patients and 24,437 controls, and 1960 LADA patients and 5583 controls.
  
  
  RESULTS
  For T1D, the C allele at -2221MspI and the A allele at -23HphI were associated with estimated relative risks of 2.13 (95 % CI 1.94, 2.35) and 0.46 (95 % CI 0.44, 0.48), which contributed to absolute increases of 46.76 and 46.98 % in the risk of all T1D, respectively. The estimated lambda values were 0.44 and 0.42, respectively, suggesting that a co-dominant model most likely explained the effects of -2221MspI and -23HphI on T1D. For -23HphI, the A allele carried an estimated relative risk of 0.55 (95 % CI 0.50, 0.61) for LADA and increased the risk of all LADA by 36.94 %. The λ value was 0.43, suggesting that a co-dominant model most likely explained the effect of -23HphI on LADA.
  
  
  CONCLUSIONS
  Our results support the existence of associations of INS with T1D and LADA.
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China.
authors.forename: Weihuang
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Dong
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China.
authors.forename: Baohuan
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China.
authors.forename: Lipeng
authors.initials: L
authors.lastname: Jing
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China.
authors.forename: Man
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Parasitology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. guangyangphd@gmail.com.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. jcxphd@gmail.com.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Jing
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D018598:Minisatellite Repeats / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics
keywords: Epidemiology; Genetic association; INS VNTR; LADA; Meta-analysis; T1D