Summary
The insulin receptor has been proposed as a candidate gene for the inherited defect in Type 2 (non-insulin-dependent) diabetes mellitus and we therefore studied three restriction fragment length polymorphic sites, two revealed with the enzyme Sst1 and one by Rsa1, using two insulin receptor cDNA probes in 131 Caucasian Type 2 diabetic patients and 94 control subjects. The frequency of the six alleles studied did not differ significantly between the two groups. However, one allele, a 6.2 kilobase Rsa1 fragment (R+), was found more frequently in those diabetic subjects (n=48) with a positive family history of diabetes (R+frequency=0.48) compared to those diabetic subjects (n=63) with a negative family history (R+frequency=0.34, p< 0.05). These results suggest that this polymorphism may be a linkage marker for the genetic defect in a subgroup of Type 2 diabetic patients with a positive family history.
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References
Barnett AH, Eff C, Leslie RD, Pyke DA (1981) Diabetes in identical twins: a study of 200 pairs. Diabetologia 20: 87–93
Olefsky JM, Ciaraldi TP, Kolterman OG (1985) Mechanism of insulin resistance in non-insulin-dependent (type II) diabetes. Am J Med 79: 12–22
O'Rahilly SP, Nugent Z, Rudenski AS, Hosker JP, Burnett MA, Darling P, Turner RC (1986) Beta-cell dysfunction rather than insulin insensitivity is the primary defect in familial type 2 diabetes. Lancet I: 360–363
Ullrich A, Bell JR, Chen EY et al. (1985) Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature 313: 756–761
Kadowaki T, Bevins CL, Cama A et al. (1988) Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance. Science 240: 787–790
Moller DE, Flier JS (1988) Detection of an alteration in the insulin receptor gene in a patient with insulin resistance, acanthosis nigricans and the polycystic ovary syndrome (type A insulin resistance). N Engl J Med 319: 1526–1529
Comi RJ, Grunberger G, Gorden P (1987) Relationship of insulin binding and insulin-stimulated tyrosine kinase activity is altered in type II diabetes. J Clin Invest 79: 453–462
Freidenberg GR, Henry RR, Klein HH, Reichart DR, Olefsky JM (1987) Decreased kinase activity of insulin receptors from adipocytes of non-insulin-dependent diabetic subjects. J Clin Invest 79: 240–250
Caro JF, Ittoop O, Pories WJ et al. (1986) Studies on the mechanism of insulin resistance in the liver from humans with non-insulin-dependent diabetes. J Clin Invest 78: 249–258
Mandarino L, Campbell P, Gerich J (1984) Abnormal coupling of insulin receptor binding in non-insulin-dependent diabetes. Am J Physiol 247: E688-E692
Yang-Feng TL, Franke U, Ullrich A (1985) Gene for human insulin receptor: localization to a site on chromosome 19 involved in pre-B-cell leukemia. Science 228: 728–731
Seino S, Seino M, Bell GI (1990) Human insulin receptor gene: partial sequence and amplification of exons by polymerase chain reaction. Diabetes 39: 129–133
Elbein SC, Corsetti L, Ullrich A, Permutt MA (1986) Multiple restriction fragment length polymorphisms at the insulin receptor locus: a highly informative marker for linkage analysis. Proc Natl Acad Sci USA 83: 5223–5227
McClain DA, Henry RR, Ullrich A, Olefsky JM (1988) Restriction fragment length polymorphism in insulin-receptor gene and insulin resistance in NIDDM. Diabetes 37: 1071–1075
McGill J, Corsetti L, Elbein SC (1987) Restriction fragment length polymorphism at the insulin receptor in a population of diabetic and non-diabetic Blacks. Diabetes 36 [Suppl 1]: 21A (Abstract)
Galton DJ, Trembath RC (1988) Genetic variants of the insulin receptor in type 2 (non-insulin-dependent) diabetes mellitus. Biomed Biochim Acta 47: 323–327
Xiang K-S, Cox NJ, Sanz N, Huang P, Karam JH, Bell GI (1989) Insulin-receptor and apoprotein genes contribute to development of NIDDM in Chinese Americans. Diabetes 37: 17–23
Raboudi SH, Mitchell BD, Stern MP, Eifler CW, Haffner FM, Hazuda HP, Frazier ML (1989) Type II diabetes mellitus and polymorphisms of insulin-receptor gene in Mexican Americans. Diabetes 38: 975–980
World Health Organisation Expert Committee on Diabetes Mellitus Second Report (1980) WHO Technical Report Series 646
Ferns GAA, Ritchie C, Stocks J, Galton DJ (1985) Genetic polymorphisms of apoprotein C-III and insulin in survivors of myocardial infarction. Lancet II: 300–303
Feinberg AP, Vogelstein B (1983) A technique for radio-labelling DNA restriction endonuclease fragments to high specific activity. Analyt Biochem 132: 6–13
Elbein SC (1989) Molecular and clinical characterization of an insertional polymorphism of the insulin-receptor gene. Diabetes 38: 737–743
Morgan R, Bishop A, Peters JR, Owens DR, Rees A (1989) Two DNA sequence variants at the insulin receptor gene locus revealed by the restriction endonuclease Sst 1. Diabetic Med 6 [Suppl 1]: A21 (Abstract)
Hitman GA, Karir PK, Mohan V, Rao PV, Kohner EM, Levy JC, Mather H (1987) A genetic analysis of type-2 (non-insulin-dependent) diabetes mellitus in Punjabi Sikhs and British Caucasoid patients. Diabetic Med 4: 526–530
Li SR, Oelbaum RS, Stocks J, Galton DJ (1988) DNA polymorphisms of the insulin receptor gene in Japanese subjects with non-insulin dependent diabetes mellitus. Hum Hered 38: 273–276
O'Rahilly S, Trembath RC, Patel P, Galton DJ, Turner RC, Wainscoat JS (1988) Linkage analysis of the human insulin receptor gene in Type 2 (non-insulin-dependent) diabetic families and a family with maturity onset diabetes of the young. Diabetologia 31: 792–797
Cox NJ, Epstein PA, Speilman RS (1989) Linkage studies on NIDDM and the insulin and insulin-receptor genes. Diabetes 38: 653–658
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Oelbaum, R.S., Bouloux, P.M.G., Li, S.R. et al. Insulin receptor gene polymorphisms in Type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 34, 260–264 (1991). https://doi.org/10.1007/BF00405085
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DOI: https://doi.org/10.1007/BF00405085