Association study between CD30 and CD30 ligand genes and type 1 diabetes in the Japanese population.
CD30-CD30 ligand (CD30L) signal transduction appears to protect against autoimmune diabetes by preventing expansion of autoreactive T cells and suppressing Th1-cytokine response. The purpose of this study was to determine whether CD30 or CD30L genes serve as a novel susceptibility gene for type 1 diabetes in humans. We screened CD30 and CD30L genes for polymorphisms in Japanese patients with type 1 diabetes and control subjects. Then, association studies were performed between each of the identified polymorphisms and type 1 diabetes. Direct-sequencing analysis of the CD30 and CD30L genes revealed four polymorphisms: one in the CD30 gene (-201G/A from the transcription start site), and three in the CD30L gene [CA repeat in the promoter, 276G/A in the exon 3, -73T/C in the intron 3 (IVS3 -73T/C)]. Association studies revealed no association between the CD30 and CD30L genes and type 1 diabetes in the whole population. In the female and male subpopulations, however, the frequency of (CA)(9) allele of the CD30L gene promoter or T allele of IVS3 -73T/C polymorphism in the CD30L gene was slightly higher in female patients with type 1 diabetes than that in control females. In conclusion, we could not find significant association between CD30 or CD30L genes and type 1 diabetes, but (CA)(9) allele in the promotor or T allele of -73T/C in intron 3 in CD30L gene might play a minor role in the pathogenesis of type 1 diabetes, only in the Japanese female population.
Ahmed
S
S
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ihara
K
K
Bassuny
W M
WM
Kuromaru
R
R
Kohno
H
H
Miyako
K
K
Matsuura
N
N
Iwata
I
I
Nagafuchi
S
S
Hara
T
T
D000293:Adolescent; D053285:CD30 Ligand; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D017730:Ki-1 Antigen / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D053285:CD30 Ligand; D017730:Ki-1 Antigen; D008562:Membrane Glycoproteins; C505774:TNFSF8 protein, human