The polymorphism linked to the human insulin gene: its lack of association with either IDDM or NIDDM in Japanese

Takeda, Jun; Seino, Yutaka; Fukumoto, Hirofumi; Koh, Gyohan; Otsuka, Akio; Ikeda, Masaki; Kuno, Shotaro; Yawata, M; Moridera, Kuniyasu; Morita, Takashi; Tsuda, Kinsuke; Imura, Hiroo

doi:10.1530/acta.0.1130268

Cited by 17 publications

(10 citation statements)

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“…In one study, a weak association (P = 0.025) of class 1 alleles with NIDDM was found in Whites (30). However, no association of this class of polymorphic allele with NIDDM was found in either American Blacks (29), Pima Indians (36), Nauruans (37), Japanese (38)(39)(40), or Chinese Americans (41). The larger racially specific studies are summarized in Table 2.…”

Section: Association Of Insulin-gene Polymorphisms With Diabetesmentioning

confidence: 99%

Insulin Gene in Diabetes Analysis Through RFLP

Permutt

Elbein²

1990

Diabetes Care

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Insulin deficiency is a prominent feature of non-insulin-dependent (NIDDM) and insulin-dependent (IDDM) diabetes mellitus that could result from defects in the insulin gene. Cloning of this gene has permitted molecular-genetic studies including the definition of multiple-DNA-sequence polymorphisms detected with restriction endonucleases, or restriction-fragment-length polymorphisms (RFLPs), and the mapping of the insulin gene to the short arm of chromosome 11 adjacent to the insulinlike growth factor II (IGF-II) and tyrosine hydroxylase genes. The combined RFLPs for the insulin, IGF-II, and tyrosine hydroxylase genes make this a highly informative locus for genetic studies of the insulin gene in diabetes. Early studies of an RFLP consisting of variable-number tandem repeats (VNTR) of DNA near the insulin gene suggested an association of certain alleles with approximately 170 copies of the repeat unit with NIDDM. Although subsequent studies in NIDDM did not confirm this association, an association of different alleles defined by approximately 40 copies of the repeat unit in this VNTR region with IDDM has been demonstrated in multiple studies. This VNTR region and the multiple other RFLPs for this region have been used in linkage analysis to study the segregation of insulin genes in families. These studies have failed to demonstrate a major significant role for insulin-gene defects in NIDDM, maturity-onset diabetes of the young, or IDDM in American Blacks and Whites and under various models of inheritance. Several pedigrees with diabetes and defects of the insulin gene have been described, however, and a minor role for this gene in NIDDM cannot be eliminated from available studies. Similarly, the association studies of the insulin gene and IDDM suggest a minor modifying role undetectable in pedigree studies. The role of defects in or near the insulin gene in a small subset of NIDDM or in IDDM must await direct investigation of the insulin gene in diabetic individuals with the most recent methods for gene amplification and sequence analysis.

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Section: Association Of Insulin-gene Polymorphisms With Diabetesmentioning

confidence: 99%

Insulin Gene in Diabetes Analysis Through RFLP

Permutt

Elbein²

1990

Diabetes Care

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“…In addition, we have found a lower heterozygosity (0.11), as RCMH showed 0.30 [7]. Although some reports suggest that polymorphism of this site of the insulin gene, which was first described as an isolated mutation, can be used as a genetic marker for diabetes mellitus [2,3], there was no significant difference in the frequency of the Pst I positive allele among normal subjects, NIDDM, and IDDM in Japanese, as shown also by our previous study of RFLP of the 5' portion of the human insulin gene [4]. It is known that there is disequilibrium in the linkage between this Pst I polymorphism and hypervariable region 5' to the insulin gene [6], but [6].…”

Section: Discussionmentioning

confidence: 51%

“…It is important to know whether or not this polymorphism is associated with Proinsulin Kyoto. RFLP analysis of the insulin gene may also provide a genetic marker of diabetes mellitus [4,5]. Since the frequency of Pst I polymorphism in the 3'-untranslated region of the insulin gene is different in several races [6,7], in the present study we investigated the association of Pst I polymorphism in normal Japanese subjects and patients with IDDM and NIDDM.…”

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confidence: 99%

Hind III Site Causing Proinsulin Kyoto and Pst I Site Polymorphism of the Insulin Gene in Japanese: Its Lack of Association with Either IDDM or NIDDM.

et al. 1994

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Abstract. The gene encoding Proinsulin Kyoto has been isolated and characterized by DNA sequencing, indicating that the molecular basis of the disorder is a G-T point mutation in the insulin gene which creates a Hind III site. In addition, in the 3'-untranslated region of the mutant insulin gene, a Pst I site negative, a type allele was found, and in the normal gene, a Pst I site positive, f3 type allele was found. In order to clarify the frequency of the mutation and to determine whether this mutation is associated with diabetes mellitus or not, we have investigated Hind III polymorphism in 91 normal Japanese subjects and patients with IDDM and NIDDM. No cases with the Proinsulin Kyoto gene were found among the subjects examined. Secondly, to determine whether this a type allele is associated with DM in Japanese, we investigated Pst I polymorphism in the same subjects. The frequencies of the a type and 13 type alleles were 92% and 8%, respectively. No significant difference in genotypic frequency was found among normal, NIDDM, and IDDM. We conclude that the Proinsulin Kyoto gene is not a common cause of DM and the occurrence of the a type insulin gene in Japanese diabetes is more frequent than in other races, so this Pst I polymorphism is not a marker for diabetes mellitus in Japanese. Key words: ProinsulinKyoto, NIDDM, Insulin gene, RFLP, Pst I site.(Endocrine journal 41: [71][72][73][74]1994) A NEW TYPE OF hyperproinsulinemia has recently been reported by our laboratory in a 65-yrold non-obese Japanese man who developed NIDDM [1]. A family study revealed that his son and daughter also showed signs of fasting hyperinsulinemia.Analysis of their sera by reverse phase high performance liquid chromatography demonstrated a minor peak of human insulin (5%) and a major peak of Proinsulin-like material (95%). Amplification and sequencing of the products of the insulin gene by polymerase chain reac-

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“…In Japan, the INS VNTR region is less polymorphic, and approximately 95% of Japanese are homozygous for class I alleles, which makes it difficult to assess the role of INS-VNTR in the development of type 1 diabetes in the Japanese. In fact, no significant differences in class I or class III alleles are found between Japanese patients with type 1 diabetes and control subjects [34,35]. Awata and coworkers studied how the exact length, in number of RUs, of class I alleles influences disease susceptibility in Japanese subjects.…”

Section: Insulin Gene Ia-2 Genementioning

confidence: 99%

Current knowledge of Japanese type 1 diabetic syndrome

Abiru

Kawasaki

Eguch

2002

Diabetes Metabolism Res

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The Japanese have one of the lowest incidence of childhood type 1 diabetes in the world, but the incidence of this disease is clearly increasing within the Japanese population, as reported in several European countries. Latent autoimmune diabetes mellitus in adult (LADA) patients are also likely to have a lower incidence compared to Caucasians. Among the non-autoimmune (type 1B) diabetes in Japanese adults, there exists a novel subtype of type 1 diabetes characterized by extremely rapid onset and pancreatic exocrine inflammation. HLA and non-HLA gene associations to type 1 diabetes may vary depending on ethnic origin. Highly susceptible HLA haplotypes of type 1 diabetes observed in Caucasian patients are not found in Japanese patients, while protective HLA haplotypes are similar. Association studies of non-HLA genes have identified several candidate genes that influence the heterogeneity of disease phenotypes as well as disease susceptibility to type 1 diabetes. The INS-VNTR gene or polymorphisms of MICA gene are associated with susceptibility, whereas a certain allele of MICA gene and IL-10 gene polymorphism are associated with clinical heterogeneity of the disease. An expression of multiple autoantibodies to a biochemically determined autoantigen confers a high risk for progression to type 1 diabetes. The combined evaluation of multiple autoantibodies is more sensitive than is ICA testing for the diagnosis of type 1 diabetes. A high titer of GAD autoantibody has the predictive value of future insulin deficiency in patients with LADA. For accurate predictive strategies of future insulin deficiency, combinational multiple autoantibodies analysis or genetic determination should be considered for effective immune intervention.

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The polymorphism linked to the human insulin gene: its lack of association with either IDDM or NIDDM in Japanese

Cited by 17 publications

References 0 publications

Insulin Gene in Diabetes Analysis Through RFLP

Insulin Gene in Diabetes Analysis Through RFLP

Hind III Site Causing Proinsulin Kyoto and Pst I Site Polymorphism of the Insulin Gene in Japanese: Its Lack of Association with Either IDDM or NIDDM.

Current knowledge of Japanese type 1 diabetic syndrome

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