Genetics of type 1 diabetes in Asian and Caucasian populations.
Among candidate genes for type 1 diabetes, HLA, INS, CTLA4, PTPN22 and SUMO4 have been shown to be associated with the disease in Caucasian populations. To clarify the similarities and differences in the contribution of these genes to type 1 diabetes between Asian and Caucasian populations, association of these genes with type 1 diabetes was studied in a large number of samples in Japanese and Korean populations. Class II HLA was strongly associated with type 1 diabetes in both Asian and Caucasian populations, but haplotypes associated with type 1 diabetes were markedly different due to difference in the presence and absence of haplotypes in each population. INS was consistently associated with type 1 diabetes in both Japanese and Caucasian populations, but frequency of disease-associated haplotype was markedly high in Japanese general population. CTLA4 was associated with type 1 diabetes only in a subset of patients with type 1 diabetes complicated with AITD in Japanese. A variant (R620W) of PTPN22 was associated with type 1 diabetes and other autoimmune diseases in Caucasians, but the variant was absent in Asians. SUMO4 was associated with type 1 diabetes in Asians, but not in Caucasian, suggesting a genetic heterogeneity among diverse ethnic groups. Trans-racial study with a large number of samples in both Asian and Caucasian populations will contribute to genetic dissection of type 1 diabetes and identification of causative variants.
Ikegami
Hiroshi
H
Department of Endocrinology, Metabolism and Diabetes, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan. ikegami@med.kindai.ac.jp
Kawabata
Yumiko
Y
Noso
Shinsuke
S
Fujisawa
Tomomi
T
Ogihara
Toshio
T
D000069594:Abatacept; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D005190:Family; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D018796:Immunoconjugates / Q000235:genetics; D007328:Insulin / Q000235:genetics; D007564:Japan; D009154:Mutation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics; D013045:Species Specificity; D044465:White People / Q000235:genetics*
D006680:HLA Antigens; D018796:Immunoconjugates; D007328:Insulin; C489647:SUMO4 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D000069594:Abatacept; C516765:PTPN22 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases