Association of polymorphism in the interferon gamma gene with IDDM.
Cytokines may play important roles in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). We analysed a dinucleotide repeat polymorphism within the first intron of the interferon gamma (IFN-gamma) gene in Japanese diabetic patients (175 IDDM and 145 non-insulin-dependent diabetes mellitus) and 267 control subjects. A significant difference was observed in the global allele distribution of the polymorphism between the IDDM and control groups (p = 0.039). The difference from the control group was more evident in the patients whose insulin therapy started within 1 year from onset (p = 0.006) or in the young-onset (< 10 years) patients (p = 0.0006). The alleles "3" and "6" were increased in the IDDM patients, and a significant increase in the frequency of the "3/6" genotype was observed in the IDDM patient group (9.1%, RR 2.9, p = 0.010), in the patients with initial insulin therapy less than 1 year from onset (10.6%, RR 3.4, p = 0.004), or in the young-onset patients (16.7%, RR 5.7, p = 0.0003) in comparison to the control subjects (3.4%). There was a tendency towards frequent occurrence of clinical characteristics which reflect young or abrupt onset of diabetes or both, and depletion of insulin secretion capacity in the patients with "3/6" or "6/6" in comparison to the patients with other genotypes. These results suggest that the IFN-gamma gene region may contribute to the pathogenesis of IDDM and could be a genetic marker for IDDM.
Awata
T
T
Department of Pathology, University of Massachusetts Medical Center, Worcester.
Matsumoto
C
C
Urakami
T
T
Hagura
R
R
Amemiya
S
S
Kanazawa
Y
Y
D000328:Adult; D000483:Alleles; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic
D005819:Genetic Markers; D007371:Interferon-gamma; D004247:DNA