Polymorphism in the transmembrane region of the MICA gene and type 1 diabetes.
Although MHC class II genes have a stronger association with type 1 diabetes than MHC class I genes, studies have shown that MHC class I molecules play an independent role in the etiology of type 1 diabetes, and the existence of susceptibility genes within a segment of MHC between the HLA-B and TNF genes has been predicted, where MHC class I chain-related gene A (MICA) resides. MICA has a triplet repeat polymorphism in the transmembrane region consisting of five alleles. We analyzed this polymorphism in 162 unrelated children (82 boys) with type 1 diabetes (age at diagnosis 7.01 +/- 3.76 yr) and 154 randomly selected unrelated children (87 boys), age 2.81 +/- 2.12 yr. Phenotype frequency of allele A9 in children with type 1 diabetes was significantly higher than in controls (RR = 2.42, 95% CI = 1.52-3.85, p = 0.000162, pc = 0.00081). Gene frequency of allele A9 was also significantly higher in children with type 1 diabetes when compared with control children (RR = 2.73, 95% CI = 1.85-4.03, p = 2.62 x 10(-7), pc = 1.31 x 10(-6)). This study demonstrates that MICA allele A9 confers risk of type 1 diabetes.
Lee
Y J
YJ
Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.
Huang
F Y
FY
Wang
C H
CH
Lo
F S
FS
Tsan
K W
KW
Hsu
C H
CH
Huang
C Y
CY
Chang
S C
SC
Chang
J G
JG
D000483:Alleles; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D005787:Gene Frequency; D005914:Globins / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011897:Random Allocation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D005914:Globins