PMID- 22069271
OWN - NLM
STAT- MEDLINE
DCOM- 20120325
LR  - 20221207
IS  - 1520-7560 (Electronic)
IS  - 1520-7552 (Linking)
VI  - 27
IP  - 8
DP  - 2011 Nov
TI  - Analysis of the HLA and non-HLA susceptibility loci in Japanese type 1 diabetes.
PG  - 844-8
LID - 10.1002/dmrr.1234 [doi]
AB  - BACKGROUND: We previously reported the associations of human leukocyte antigen 
      (HLA) (DRB1 and DQB1), INS, CTLA4, IL2RA, ERBB3 and CLEC16A with Japanese type 1 
      diabetes (T1D). In this study, we jointly analysed these loci in addition to 
      IFIH1 and IL7R. METHODS: A maximum of 790 T1D patients and 953 control subjects 
      were analysed. HLA was determined by sequencing-based typing. Seven non-HLA 
      single nucleotide polymorphisms were genotyped using TaqMan assay. RESULTS: HLA 
      DRB1*0405, DRB1*0901 and DRB1*0802-DQB1*0302 haplotypes were positively 
      associated with T1D, while the DRB1*15 haplotypes were negatively associated. 
      Non-HLA single nucleotide polymorphisms, INS, IL2RA, ERBB3, CLEC16A and IL7R were 
      associated with T1D. By a prediction model using the HLA loci alone (HLA model) 
      or the non-HLA loci alone (non-HLA model), it was revealed that the cumulative 
      effect of the non-HLA model was much weaker than that of the HLA model (average 
      increase in odds ratio: 1.17 versus 3.14). Furthermore, the area under the 
      receiver operating characteristic curve of the non-HLA model was also much 
      smaller than that of the HLA model (0.65 versus 0.81, p<10(-11)). Finally, a 
      patient-only analysis revealed the susceptible HLA haplotypes and the risk allele 
      of INS to be negatively associated with slower onset of the disease. In addition, 
      the DRB1*0901 haplotype and the risk alleles of ERBB3, CLEC16A and CTLA4 were 
      positively associated with the co-occurrence of thyroid autoimmunity. 
      CONCLUSIONS: Although several non-HLA susceptibility genes in Japanese were 
      confirmed trans-racially and appear to contribute to the heterogeneity of the 
      clinical phenotypes, the cumulative effect on the ability to predict the 
      development of T1D was weak.
CI  - Copyright (c) 2011 John Wiley & Sons, Ltd.
FAU - Yamashita, Hisakuni
AU  - Yamashita H
AD  - Department of Endocrinology and Diabetes, Faculty of Medicine, Saitama Medical 
      University, Saitama, Japan.
FAU - Awata, Takuya
AU  - Awata T
FAU - Kawasaki, Eiji
AU  - Kawasaki E
FAU - Ikegami, Hiroshi
AU  - Ikegami H
FAU - Tanaka, Shoichiro
AU  - Tanaka S
FAU - Maruyama, Taro
AU  - Maruyama T
FAU - Shimada, Akira
AU  - Shimada A
FAU - Nakanishi, Koji
AU  - Nakanishi K
FAU - Takahashi, Kazuma
AU  - Takahashi K
FAU - Kobayashi, Tetsuro
AU  - Kobayashi T
FAU - Kawabata, Yumiko
AU  - Kawabata Y
FAU - Miyashita, Yumi
AU  - Miyashita Y
FAU - Kurihara, Susumu
AU  - Kurihara S
FAU - Morita-Ohkubo, Tomoko
AU  - Morita-Ohkubo T
FAU - Katayama, Shigehiro
AU  - Katayama S
CN  - Japanese Study Group on Type 1 Diabetes Genetics
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Diabetes Metab Res Rev
JT  - Diabetes/metabolism research and reviews
JID - 100883450
RN  - 0 (Autoantibodies)
RN  - 0 (CLEC16A protein, human)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (IL2RA protein, human)
RN  - 0 (Insulin)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Monosaccharide Transport Proteins)
SB  - IM
MH  - Age of Onset
MH  - Asian People/genetics
MH  - Autoantibodies/analysis
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease/genetics
MH  - HLA-DR Antigens/genetics
MH  - HLA-DRB1 Chains/genetics
MH  - Haplotypes
MH  - Histocompatibility Antigens Class I/genetics
MH  - Histocompatibility Antigens Class II/*genetics
MH  - Humans
MH  - Insulin/genetics
MH  - Interleukin-2 Receptor alpha Subunit/genetics
MH  - Lectins, C-Type/genetics
MH  - Male
MH  - Monosaccharide Transport Proteins/genetics
MH  - Polymorphism, Single Nucleotide
MH  - Thyroid Gland/immunology
FIR - Awata, Takuya
IR  - Awata T
FIR - Ikegami, Hiroshi
IR  - Ikegami H
FIR - Kawasaki, Eiji
IR  - Kawasaki E
FIR - Kobayashi, Tetsuro
IR  - Kobayashi T
FIR - Maruyama, Taro
IR  - Maruyama T
FIR - Nakanishi, Koji
IR  - Nakanishi K
FIR - Akira
IR  - Akira
FIR - Shimada
IR  - Shimada
FIR - Takahashi, Kazuma
IR  - Takahashi K
EDAT- 2011/11/10 06:00
MHDA- 2012/03/27 06:00
CRDT- 2011/11/10 06:00
PHST- 2011/11/10 06:00 [entrez]
PHST- 2011/11/10 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
AID - 10.1002/dmrr.1234 [doi]
PST - ppublish
SO  - Diabetes Metab Res Rev. 2011 Nov;27(8):844-8. doi: 10.1002/dmrr.1234.