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Method for estimating danger of diabetes typ B developed in the human species of Chinese bloodline and composition

A gene product, glucokinase technology, applied in the field of assessing the risk and composition of the development of type 2 diabetes in people of Chinese ancestry, can solve problems such as not disclosed

Inactive Publication Date: 2012-08-08
THE CHINESE UNIVERSITY OF HONG KONG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Mutations and polymorphisms in the glucokinase and HNF-1α genes associated with the genetic predisposition of individuals of the Chinese population to develop type 2 diabetes were initially identified in Ng, et al. (Diabetic Medicine 1999, 16:956, incorporated herein by reference) , but the manuscript does not disclose how to use these mutations and polymorphisms to identify individuals of the Chinese race who are at increased risk of developing type 2 diabetes
[0009] USPN 5,541,060 discloses the screening results of 16 French families carrying MODY and the identification of some missense mutations in the glucokinase gene, but none of the identified mutations are associated with individuals of Chinese ancestry

Method used

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  • Method for estimating danger of diabetes typ B developed in the human species of Chinese bloodline and composition
  • Method for estimating danger of diabetes typ B developed in the human species of Chinese bloodline and composition
  • Method for estimating danger of diabetes typ B developed in the human species of Chinese bloodline and composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Identification of glucokinase and hepatocyte nuclear factor 1α genes in Chinese patients with premature type 2 diabetes mellitus / MODY

[0066] This example exemplifies mutations in the glucokinase and hepatocyte nuclear factor 1α and HNF-4α genes identified in a group of Chinese patients. Mutations in the glucokinase and HNF-1α genes are relatively common in Chinese patients with early-onset type 2 diabetes, and they account for approximately 3% and 5% of current Chinese patients with early-onset type 2 diabetes, respectively.

[0067] Trial Design and Methods

[0068] subjects

[0069] This study group included 92 unrelated patients (age 34 ± 5 ​​years (mean age ± SD) range 18-40 years, 30 males, 62 females) who were diagnosed with type 2 diabetes before the age of 40 and had Positive family history (at least 1st level associated with type 2 diabetes). The mean age at diagnosis was 30 ± 5 years (age range 16-40 years). Thirteen (14%) patients met the minimum criter...

Embodiment 2

[0103] Mitochondrial DNA A3243G mutation in early or late type 2 diabetes mellitus in Hong Kong Chinese

[0104] This example exemplifies the widespread prevalence of the A3243G mutation in mitochondrial DNA among Chinese in Hong Kong, manifested in a large number of type 2 diabetics at different ages at diagnosis and clinical phenotype.

[0105] Trial Design and Methods

[0106] subjects

[0107] The experimental group consisted of 906 unrelated type 2 diabetic patients diagnosed according to the 1985 WHO (World Health Organization, 1985) criteria. This group included four groups of patients based on age at diagnosis and the presence or absence of a family history of diabetes. Groups 1 and 2 included 219 and 128 patients, respectively, who were younger at diagnosis (≤40 years), with family history of diabetes in group 1 and no family history of diabetes in group 2. Groups 3 and 4 included 211 and 348 patients, respectively, with older age at diagnosis (>40 years old) in gr...

Embodiment 3

[0133]The role of amylin gene S20G mutation in early-onset type 2 diabetes mellitus and regulation of cholesterol metabolism in Chinese

[0134] This example exemplifies the distribution of the amylin gene S20G mutation in Hong Kong Chinese with and without type 2 diabetes, and its impact on β-cell function and metabolic profile. These data are consistent with the conclusion that the S20G mutation in the amylin gene leads to the early onset of type 2 diabetes, and it is also consistent with the conclusion that it may affect fat metabolism in the Chinese population.

[0135] Trial Design and Methods

[0136] subjects

[0137] This study was approved by the Clinical Research Ethics Committee of The Chinese University of Hong Kong. Consent was obtained from each participant. For the study, 227 early-onset and 235 late-onset type 2 diabetics (defined as age at diagnosis ≤40 and >40, respectively), and 126 non-diabetic subjects (defined as fasting plasma glucose 3+) or persisten...

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Abstract

Methods and compositions for identifying mutations and polymorphisms in mutant genes encoding gene product involved in insulin secretion, for example, hepatocyte nuclear factor -1∝ glucokinase, amylin and mitochondrial DNA are disclosed. Specifically, a microchip comprising a combination of at least two different mutant genes wherein each gene comprises at least one mutation indicative of a predisposition for type-2 diabetes in a member of a Chinese population is disclosed. A kit comprising the microchip, an isolated nucleic acid, primers and probes which are specifically used to screen or identify the mutations in genes of hepatocyte nuclear factor-1∝ glucokinase, amylin and mitochondrial DNA are also disclosed.

Description

field of invention [0001] The present invention relates to identification and application of mutations and polymorphisms in mutant genes of wild-type genes involved in insulin secretion function, said mutations and polymorphisms are associated with increased risk of developing type 2 diabetes in Chinese individuals. The present invention is exemplified by combining mutations specifically identified in Chinese individuals with a positive family history of type 2 diabetes in genes encoding hepatocyte nuclear factor-1α, glucokinase, amylin and on mitochondrial DNA. The combination of mutated genes can be used to screen Chinese individuals for risk of developing type 2 diabetes and to provide information to physicians to prescribe different specific treatments to patients. Background of the invention [0002] Although people of Chinese ancestry comprise >20% of the world's population (Chan, et al. (1997) 20:1785), little is known about the genetic factors associated with dev...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/68C07H21/00C07K14/435C07K14/47C07K14/575C12N9/12C12Q1/6883
CPCC12Q2600/156C07K14/4702C12Q1/6883C12N9/1205C07K14/575
Inventor 朱利安.A.J.H.克里奇利玛吉.C.Y.NG少.C.李克莱夫.S.科克拉姆朱利安娜.C.N.陈
Owner THE CHINESE UNIVERSITY OF HONG KONG
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