title: Stromal-cell derived factor-1 chemokine gene variant is associated with type 1 diabetes age at onset in Japanese population.
abstract: 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.
authors.affiliation: First Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Ide
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawasaki
authors.forename: Norio
authors.initials: N
authors.lastname: Abiru
authors.forename: Fuyan
authors.initials: F
authors.lastname: Sun
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fukushima
authors.forename: Ryoko
authors.initials: R
authors.lastname: Takahashi
authors.forename: Hironaga
authors.initials: H
authors.lastname: Kuwahara
authors.forename: Naruhiro
authors.initials: N
authors.lastname: Fujita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kita
authors.forename: Katsuya
authors.initials: K
authors.lastname: Oshima
authors.forename: Shigeo
authors.initials: S
authors.lastname: Uotani
authors.forename: Hironori
authors.initials: H
authors.lastname: Yamasaki
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kawabata
authors.forename: Tomomi
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegami
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
mesh_terms: 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
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D000949:Histocompatibility Antigens Class II