Stromal-cell derived factor-1 chemokine gene variant is associated with type 1 diabetes age at onset in Japanese population.
Stromal-cell derived factor-1 (SDF-1) is a powerful chemokine that upregulates T-cell migration and activation. The gene for SDF-1 is located near type 1 diabetes susceptibility locus IDDM10, suggesting a contribution by SDF-1 to the induction of diabetes. Recently the role of SDF-1 gene polymorphism in the clinical presentation of type 1 diabetes in French population has been reported. To test the putative involvement of SDF-1 gene polymorphism in predisposition to or clinical heterogeneity of type 1 diabetes in Japanese population, we conducted the case-control study. The SDF1-3'A variant (801 G to A in the 3'-untranslated region) was determined by the polymerase chain reaction-restriction fragment length polymorphism technique in 184 patients with abrupt-onset type 1 diabetes and 106 healthy control subjects. No significant difference in allele and genotype frequencies of SDF1-3'A variant was found between type 1 diabetic patients and healthy controls. However, the SDF1-3'A variant was strongly associated with early-onset diabetes in a recessive model (AA versus AG + GG, p = 0.017). The mean age-at-onset in patients carrying SDF1-3'AA genotype was significantly younger than that in patients with SDF1-3' AG or GG genotype (p = 0.028). The frequencies of SDF1-3' A variant were significantly increased in HLA-DR4/9 patients compared with non-DR4/9 patients (p = 0.008). These results suggest that the SDF-1 gene polymorphism is associated with the age-at-onset of type 1 diabetes in Japanese population.
Ide
Akane
A
First Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Kawasaki
Eiji
E
Abiru
Norio
N
Sun
Fuyan
F
Fukushima
Tetsuya
T
Takahashi
Ryoko
R
Kuwahara
Hironaga
H
Fujita
Naruhiro
N
Kita
Atsushi
A
Oshima
Katsuya
K
Uotani
Shigeo
S
Yamasaki
Hironori
H
Yamaguchi
Yoshihiko
Y
Kawabata
Yumiko
Y
Fujisawa
Tomomi
T
Ikegami
Hiroshi
H
Eguchi
Katsumi
K
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D000949:Histocompatibility Antigens Class II