title: Polymorphism screening of the insulin receptor-related receptor gene (INSRR) on 1q in Pima Indians.
abstract: INSRR coding for the insulin receptor-related receptor (IRR) is located within the 1q21-q23 region linked with type-2 diabetes mellitus in Pima Indians and Caucasians. Although the ligand and biological function of this receptor are not yet known, its tyrosine kinase phosphorylates proteins involved in insulin signaling, and IRR may also play a role in the control of the insulin producing beta-cell mass. Therefore, defects in INSRR could contribute to susceptibility to type-2 diabetes. By screening the 22 exons, 5' and 3' flanking sequences, and most introns in 20 Pima Indians and one Caucasian control, we detected nine diallelic variants, including eight single nucleotide polymorphisms (SNPs), and a length polymorphism involving a 26-nt motif. In this study sample, four of the identified SNPs were rare, while the remaining five common variants located within 4.5 kb from the 3' end of the gene were in linkage disequilibrium. When analysed in selected diabetic and non-diabetic Pimas, none of the markers was associated with the disease. We conclude that INSRR has no detectable mutations contributing to diabetes in the Pima Indians. However, information on the novel markers may prove useful for association studies of this candidate gene in other populations.
authors.affiliation: Clinical Diabetes and Nutrition Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, 4212 North 16th Street, Phoenix, AZ 85016, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Wolford
authors.forename: F
authors.initials: F
authors.lastname: Thameem
authors.forename: C
authors.initials: C
authors.lastname: Bogardus
authors.forename: M
authors.initials: M
authors.lastname: Prochazka
mesh_terms: D000328:Adult; D001130:Arizona; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D009679:Nuclear Family; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011972:Receptor, Insulin / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D011972:Receptor, Insulin; C066542:insulin receptor-related receptor