MUTATIONS IN THE GLUCOKINASE GENE ARE NOT A MAJOR CAUSE OF LATE-ONSET TYPE-2 (NON-INSULIN-DEPENDENT) DIABETES-MELLITUS IN JAPANESE SUBJECTS

被引：13

作者：

NISHI, S

HINATA, S

MATSUKAGE, T

TAKEDA, J

ICHIYAMA, A

BELL, GI

YOSHIMI, T

机构：

[1] Second Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu

[2] First Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu

[3] Howard Hughes Medical Institute, Departments of Biochemistry and Molecular Biology and Medicine, University of Chicago

来源：

DIABETIC MEDICINE | 1994年 / 11卷 / 02期

关键词：

GLUCOKINASE; GENETICS; INSULIN SECRETION;

D O I：

10.1111/j.1464-5491.1994.tb02019.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The role of the glucokinase gene in the development of diabetes in a group of 349 Japanese subjects with late-onset Type 2 diabetes was examined. These diabetic subjects and 197 non-diabetic controls were typed at two simple tandem repeat DNA polymorphisms in the glucokinase gene termed GCK2 and GCK3. Six and five alleles were evident in Japanese subjects at GCK2 and GCK3, respectively. There were no significant differences in allele, genotype or haplotype frequencies between diabetic and normal groups. In addition, the glucokinase gene of 340 diabetic and 170 non-diabetic Japanese subjects was screened for mutations using single strand conformation polymorphism analysis. Four nucleotide substitutions were identified: a silent substitution in exon 4 in the codon for proline 145 (CCC-->CCG), and A-->T, C-->G, and C-->A substitutions in introns lb, 3, and 5, respectively. There were no significant differences in the frequencies of these nucleotide substitutions between diabetic and non-diabetic groups. These results suggest that glucokinase gene defects are not a major cause of late-onset Type 2 diabetes in Japanese subjects.

引用

页码：193 / 197

页数：5

共 24 条

[1]

Kitazawa K, Murakami K, Goto Y, Hamazaki S., Prevalence of diabetes mellitus detected by 75g 0GTT in Tokyo, Tohoku J Exp Med, 141, pp. 229-234, (1983)

[2]

Rotter JI, Vadheim CM, Rimoin DL., Genetics of diabetes mellitus, Diabetes Mellitus: Theory and Practice, pp. 378-413, (1990)

[3]

Vionnet N, Stoffel M, Takeda J, Yasuda K, Bell GI, Zouali H, Et al., Nonsense mutation in the glucokinase gene causes early‐onset non‐insulin‐dependent diabetes mellitus, Nature, 356, pp. 721-722, (1992)

[4]

Stoffel M, Froguel, Takeda J, Zouali H, Vionnet N, Nishi S, Et al., Human glucokinase gene: isolation, characterization, and identification of two missense mutations linked to early‐onset non‐insulin‐dependent (type 2) diabetes mellitus, Proc Natl Acad Sci USA, 89, pp. 7698-7702, (1992)

[5]

Froguel P, Zouali H, Vionnet N, Velho G, Vaxillaire M, Sun F, Et al., Familial hyperglycemia due to mutations in glucokinase‐Definition of a subtype of diabetes mellitus, N Engl J Med, 328, pp. 697-702, (1993)

[6]

Gidh-Jain M, Takeda J, Xu LZ, Lange AJ, Vionnet N, Stoffel M, Et al., Glucokinase mutations associated with non‐insulin‐dependent (type 2) diabetes mellitus have decreased enzymatic activity: Implication for structure/function relationships, Proceedings of the National Academy of Sciences, 90, pp. 1932-1936, (1993)

[7]

Stoffel M, Patel P, Lo Y-MD, Hattersley AT, Lucassen AM, Page R, Et al., Missense glucokinase mutation in maturity‐onset diabetes of the young and mutation screening in late‐onset diabetes, Nature Genetics, 2, pp. 153-156, (1992)

[8]

Katagiri H, Asono T, Ishihara H, Inukai K, Anai M, Miyazaki J, Et al., Nonsense mutation of glucokinase gene in late‐onset non‐insulin‐dependent diabetes mellitus, Lancet, 340, pp. 1316-1317, (1992)

[9]

Sakura H, Eto K, Kadowaki H, Simokawa K, Ueno H, Koda N, Et al., Structure of the human glucokinase gene and identification of a missense mutation in a Japanese patient with early‐onset non‐insulin‐dependent diabetes mellitus, J Clin Endocrinol Metabol, 75, pp. 1571-1573, (1992)

[10]

Shimada F, Makino H, Hashimoto N, Taira M, Seino S, Bell GI, Et al., Type 2 (non‐insulin‐dependent) diabetes mellitus associated with a mutation of the glucokinase gene in a Japanese family, Diabetologia, 36, pp. 433-437, (1993)

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