Functional polymorphism in Z-DNA-forming motif of promoter of SLC11A1 gene and type 1 diabetes in Japanese subjects: association study and meta-analysis.
The association of the polymorphism of the Z-DNA-forming repeats in the promoter region of SLC11A1 (solute carrier family 11 member 1), formerly designated NRAMP1 (natural resistance associated macrophage protein 1), with type 1 diabetes was studied in a total of 244 Japanese subjects. Three alleles were detected in Japanese subjects. In diabetic patients, allele 2 was less frequent and allele 3 was more frequent, albeit not significantly, than in control subjects. Allele 2 was significantly ( P < .024) less frequent whereas allele 3 was more, albeit not significantly, frequent in the younger onset group than in the control subjects. In patients with a susceptible HLA allele, DRB1*0405 or DRB1*0901 , the frequency of allele 2 was significantly ( P < .013) lower and that of allele 3 tended to be higher than that in patients without either DRB1*0405 or DRB1*0901 . The protective effect of allele 2 against type 1 diabetes and other autoimmune diseases was confirmed by meta-analysis (summary odds ratio, 0.71, 95% confidence interval, 0.53-0.96). Because allele 2 was shown to be associated with low expression of SLC11A1 and protection against another autoimmune disease, rheumatoid arthritis, the negative association of allele 2 with autoimmune type 1 diabetes in the present study suggests that a less active immune system in subjects with allele 2 may protect individuals from autoimmune diseases.
Nishino
Masanori
M
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Ikegami
Hiroshi
H
Fujisawa
Tomomi
T
Kawaguchi
Yoshihiko
Y
Kawabata
Yumiko
Y
Shintani
Maki
M
Ono
Masaya
M
Ogihara
Toshio
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D020816:Amino Acid Motifs; D044466:Asian People / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D043542:DNA, Z-Form / Q000096:biosynthesis*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D043542:DNA, Z-Form; D000099173:Natural Resistance-associated Macrophage Protein 1