Association between a polymorphism of the 65K-glutamate decarboxylase gene and insulin-dependent diabetes mellitus
- Tohoku Univ. School of Medicine, Sendai (Japan); and others
Autoimmunity against 65K-glutamate decarboxylase (GAD65), one of two forms of the {gamma}-aminobutyric acid-synthesizing enzyme, is commonly associated with insulin-dependent diabetes mellitus (IDDM). To study the predisposing effect of the GAD65 genotype on IDDM, we performed a case-control study screening an association between a newly-identified GAD65 polymorphism and IDDM in the Japanese population. The identified polymorphism was a microsatellite that was located in an intron near the 3{prime} end of the GAD65 gene consisting of variable numbers of a (CA)-dinucleotide repeat. We amplified the polymorphic region by polymerase chain reaction, and, for each individual in the control group (n=254) and the IDDM group (n=108), determined a pair of (CA)-repeat numbers, each number derived from one or the other of their alleles. In both groups we found 13 allelic variants with different repeat numbers, ranging from 19 to 31 repeats of the (CA) dinucleotide. The most frequent allelic variant in the IDDM group was 20 repeats; (CA){sub 20}. A higher frequency of a genotype containing two (CA){sub 20} alleles (p=0.005) was observed in the IDDM group (41.7%) compared with the control group (26.8%). Odds ratio (a 95% confidence interval) for a heterozygote or a homozygote of (CA){sub 20} versus a subject without (CA){sub 20} was 1.2 (0.66-2.25) and 2.23 (1.18-4.21), respectively. No significant association was observed between the (CA)-repeat genotype and the appearance of anti-GAD antibodies in the patients whose duration of the diabetes was less than 4 years (n=35). Therefore, genetic variations in GAD65 appears to be associated with IDDM susceptibility.
- OSTI ID:
- 133909
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0643
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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