Insulin receptor and insulin-responsive glucose transporter (GLUT 4) mutations and polymorphisms in a welsh type 2 (non-insulin-dependent) diabetic population

Abstract

We have recently examined the exons encoding the insulin receptor tyrosine kinase domain and GLUT 4 in 30 subjects with Type 2 (non-insulin-dependent) diabetes mellitus using a molecular scanning approach. The variant sequences Val-Met985 and Lys-Glu1068 of the insulin receptor and Val-Ile383 of GLUT 4 were each separately found in three different diabetic subjects. In a study of a Welsh population, the GLUT 4(383) variant was found in three of 160 diabetic and none of the 80 control subjects. In this study, the same group of Welsh Type 2 diabetic and control subjects was analysed using allele-specific oligonucleotide hybridisation, single nucleotide primer extension and allele-specific restriction digestion to ascertain the frequency of the two insulin receptor mutations. The Val-Met985 mutation was found in none of the 160 Welsh Caucasian Type 2 diabetic subjects and two of 80 control subjects. The Lys-Glu1068 mutation removes a Sty 1 site and digestion of amplified exon 18 with Sty 1 confirmed the presence of the mutation in the heterozygous state in the original subject. None of the Welsh diabetic or control subjects had the Glu1068 mutation. The discovery of a very common silent polymorphism at codon 130 of GLUT 4 allowed examination of the association of this locus with Type 2 diabetes using allele-specific oligonucleotide hybridisation in a subset of the Welsh subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Association of genetic variants in INS (rs689), INSR (rs1799816) and PP1G.G (rs1799999) with type 2 diabetes (T2D): a case–control study in three ethnic groups from North-West India

“…The association of A allele with T2D was also reported in a population based study in Netherland [P = 0.005; OR = 4.49, 95 % CI (1.65-12.26)] (Hart et al 1996). In contrast to these findings, studies carried out on Danish-Caucasians (Hansen et al 1997;Elbein et al 1993), American blacks (Cox et al 1989) and Welsh population (O'Rahilly et al 1992), did not show any association of INSR G>A polymorphism with impaired insulin-sensitivity and T2D.…”

Association of <i>GLUT4</i> gene variants with HbA1c level in Japanese men

“…These two mutations were later confirmed in diabetic patients in an Indian population [4]. But further analysis in British population did not suggest any association of these mutations with T2D [5]. Other studies on GLUT4 include KpnI RFLP studies in Italian, Caucasians, Chinese, and Asian Indians, American black and Japanese population which did not establish association between the KpnI RFLP and T2D [7,9].…”

“…Discovery of restriction fragment length polymorphism (RFLP) in the GLUT4 gene [3] led to series of genetic association studies in the early 90s [4][5][6][7][8][9][10]. However, these results have so far been negative.…”

Molecular mechanism of insulin resistance in type 2 diabetes mellitus: role of the insulin receptor variant forms

“…In the same study, the Met 985 variant was also detected in 1/13 control subjects. In a study of a Welsh population, the Met 985 insulin receptor variant was found in 2/80 control subjects but in 0/160 type 2 diabetic subjects, while the Glu 1068 variant was not found either in control or diabetic subjects [69]. Another study carried The amino acids underlined have been identified in other studies in addition to the original reports of Ullrich et al [14] and Ebina et al [15].…”