Biomaterial Database

Genetic analysis of the insulin receptor gene in Chinese patients with extreme insulin resistance. 1998

W J Lee, and W H Sheu, and S G Shu, and Y E Yao

Department of Medicine, Taichung Veterans General Hospital, Taiwan, ROC.

BACKGROUND Many patients with extreme insulin resistance in combination with acanthosis nigricans are reported to have defective insulin receptor genes. Because acanthosis nigricans is commonly accompanied by severe hyperinsulinemia and obesity, and obesity is a major factor in insulin resistance, this study was initiated to assess the prevalence of mutations in the insulin receptor gene in Chinese patients with extreme insulin resistance defined by hyperinsulinemia, obesity and acanthosis nigricans. METHODS Exons 1-22 of the insulin receptor gene were amplified by polymerase chain reaction (PCR) by from genomic DNA from 13 young subjects with clinical and metabolic features of extreme insulin resistance. They were also screened for nucleotide variation using single-strand conformation polymorphism (SSCP) combined with nucleotide sequence analysis. RESULTS Variant SSCP patterns were detected in exons 1, 3, 6, 11, 12 and 17 of the insulin receptor gene. However, sequencing of amplified DNA fragments revealed that none of the variations were mutations. The SSCP variant in exon 1 was caused by a novel intron polymorphism (G-->T at position 13, 5' intron), while the SSCP variant in exon 12 was caused by a novel silent polymorphism Thr789 (ACG-->ACA). Variants in exons 3 and 17 corresponded to known silent polymorphisms: Gln276 (CAA-->CAG) and His1068 (CAC-->CAT), respectively. Another three variants in exons 3, 6 and 11 were also identified as known polymorphisms in the flanking introns. In addition, two alterations, a silent polymorphism Gly8 (GGA-->GGG) and a polymorphism in the 3' flanking intron (T-->G at position 74), were observed in exon 1 of the insulin receptor gene. CONCLUSIONS Although the prevalence of insulin receptor gene mutations in this Chinese study population might be underestimated because of the sensitivity of SSCP, these results suggest that mutations at the insulin receptor locus are uncommon in subjects with features of hyperinsulinemia, obesity and acanthosis nigricans.

UI	MeSH Term	Description	Entries
D007333	Insulin Resistance	Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.	Insulin Sensitivity,Resistance, Insulin,Sensitivity, Insulin
D008297	Male		Males
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D011972	Receptor, Insulin	A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.	Insulin Receptor,Insulin Receptor Protein-Tyrosine Kinase,Insulin Receptor alpha Subunit,Insulin Receptor beta Subunit,Insulin Receptor alpha Chain,Insulin Receptor beta Chain,Insulin-Dependent Tyrosine Protein Kinase,Receptors, Insulin,Insulin Receptor Protein Tyrosine Kinase,Insulin Receptors
D005091	Exons	The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.	Mini-Exon,Exon,Mini Exon,Mini-Exons
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293	Adolescent	A person 13 to 18 years of age.	Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D016133	Polymerase Chain Reaction	In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.	Anchored PCR,Inverse PCR,Nested PCR,PCR,Anchored Polymerase Chain Reaction,Inverse Polymerase Chain Reaction,Nested Polymerase Chain Reaction,PCR, Anchored,PCR, Inverse,PCR, Nested,Polymerase Chain Reactions,Reaction, Polymerase Chain,Reactions, Polymerase Chain