title: New amino acid substitutions in the IRS-2 gene in Finnish and Chinese subjects with late-onset type 2 diabetes.
abstract: We investigated the significance of the variants of the IRS-2 gene in patients with type 2 diabetes. The entire coding part of the IRS-2 gene was screened by single-strand conformation polymorphism analysis in 40 Chinese and 40 Finnish patients with late-onset type 2 diabetes. The association of the variants of the IRS-2 gene with type 2 diabetes was studied in 85 Finnish diabetic patients and 82 Finnish control subjects and in 100 Chinese diabetic patients and 85 Chinese control subjects. The four variants predicting structural changes in the insulin receptor substrate (IRS)-2 protein included an insertion of AAC (Asn) in the Asn repeat sequence centered around codons 29-36 (allele frequencies of 0 vs. 0.6% and 1.5 vs. 0%), the Ala157Thr substitution (0 vs. 0% and 0.5 vs. 0%), the Leu647Val substitution (0.6 vs. 0% and 0 vs. 0%), and the Gly1057Asp polymorphism (31 vs. 31% and 35 vs. 30%) (P = NS for all comparisons). Furthermore, six silent variants were observed (CGC147CGG, CCC155CCG, GCC156GCT, AGT723AGC, TGT816TGC, and CCC829CCT). The Gly1057Asp polymorphism was not associated with insulin resistance or impaired insulin secretion in Finnish subjects with normal glucose tolerance (n = 295) or impaired glucose tolerance (n = 38). These data indicate that structural variants of the IRS-2 gene were uncommon in Finnish and Chinese patients with type 2 diabetes. Thus, the variants in the coding part of the IRS-2 gene are unlikely to have a major role in the development of type 2 diabetes in Finnish or Chinese subjects.
authors.affiliation: Department of Medicine, University of Kuopio, Kuopio, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Rissanen
authors.forename: R
authors.initials: R
authors.lastname: Miettinen
authors.forename: P
authors.initials: P
authors.lastname: Kärkkäinen
authors.forename: P
authors.initials: P
authors.lastname: Kekäläinen
authors.forename: J
authors.initials: J
authors.lastname: Kuusisto
authors.forename: L
authors.initials: L
authors.lastname: Mykkänen
authors.forename: P
authors.initials: P
authors.lastname: Karhapää
authors.forename: M
authors.initials: M
authors.lastname: Laakso
mesh_terms: D017668:Age of Onset; D019943:Amino Acid Substitution; D044466:Asian People; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D002681:China / Q000208:ethnology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005091:Exons; D005387:Finland; D014644:Genetic Variation; D018149:Glucose Intolerance / Q000235:genetics; D005951:Glucose Tolerance Test; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011972:Receptor, Insulin / Q000502:physiology; D012016:Reference Values; D044465:White People
chemical_list: D001786:Blood Glucose; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011972:Receptor, Insulin