PMID- 12788886
OWN - NLM
STAT- MEDLINE
DCOM- 20030701
LR  - 20220408
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 88
IP  - 6
DP  - 2003 Jun
TI  - A combination of human leukocyte antigen DQB1*02 and the tumor necrosis factor 
      alpha promoter G308A polymorphism predisposes to an insulin-deficient phenotype 
      in patients with type 2 diabetes.
PG  - 2767-74
AB  - Our previous results have suggested that genes outside the human leukocyte 
      antigen (HLA) class II locus may affect the phenotype of type 2 diabetic patients 
      from families with both type 1 and type 2 diabetes (mixed type 1/2). To study 
      whether the TNF alpha gene could be such a modifying gene, we studied TNF alpha 
      promoter polymorphisms (G-->A substitution at positions -308 and -238) in 
      relation to HLA-DQB1 genotypes in type 2 patients from mixed type 1/2 families or 
      common type 2 diabetes families as well as in patients with adult-onset type 1 
      diabetes and control subjects. The TNF alpha(308) AA/AG genotype frequency was 
      increased in adult onset type 1 patients (55%, 69 of 126), but it was similar in 
      type 2 patients from type 1/2 families (35%, 33/93) or common type 2 families 
      (31%, 122 of 395), compared with controls (33%, 95/284; P < 0.0001 vs. type 1). 
      The TNF alpha(308) A and DQB1*02 alleles were in linkage disequilibrium in type 1 
      patients (Ds = 0.81; P < 0.001 vs. Ds = 0.25 in controls) and type 2 patients 
      from type 1/2 families (Ds = 0.59, P < 0.05 vs. controls) but not in common type 
      2 patients (Ds = 0.39). The polymorphism was associated with an insulin-deficient 
      phenotype in the type 2 patients from type 1/2 families only together with 
      DQB*02, whereas the common type 2 patients with AA/AG had lower waist to hip 
      ratio [0.92 (0.12) vs. 0.94 (0.11), P = 0.008] and lower fasting C-peptide 
      concentration [0.48 (0.47) vs. 0.62 (0.46) nmol/liter, P = 0.020] than those with 
      GG, independently of the presence of DQB1*02. In conclusion, TNF alpha is 
      unlikely to be the second gene in the HLA area responsible for our previous 
      findings in type 1/2 patients. However, we could show an association between TNF 
      alpha(308) polymorphism and the phenotype of common type 2 diabetes.
FAU - Li, Haiyan
AU  - Li H
AD  - Diabetes and Endocrine Research Laboratory, Department of Endocrinology, Lund 
      University, S-20502 Malmo, Sweden. haiyan.li@ndo.mas.lu.se
FAU - Groop, Leif
AU  - Groop L
FAU - Nilsson, Anita
AU  - Nilsson A
FAU - Weng, Jianping
AU  - Weng J
FAU - Tuomi, Tiinamaija
AU  - Tuomi T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (Insulin)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Aged
MH  - Diabetes Mellitus, Type 1/genetics
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - Female
MH  - Gene Frequency
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DQ beta-Chains
MH  - Humans
MH  - Insulin/*deficiency
MH  - Male
MH  - Middle Aged
MH  - Phenotype
MH  - *Polymorphism, Genetic
MH  - Promoter Regions, Genetic/*genetics
MH  - Tumor Necrosis Factor-alpha/*genetics
EDAT- 2003/06/06 05:00
MHDA- 2003/07/02 05:00
CRDT- 2003/06/06 05:00
PHST- 2003/06/06 05:00 [pubmed]
PHST- 2003/07/02 05:00 [medline]
PHST- 2003/06/06 05:00 [entrez]
AID - 10.1210/jc.2002-020506 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2003 Jun;88(6):2767-74. doi: 10.1210/jc.2002-020506.