Abstract
Fifty-two patients and 36 controls were compared in a search for insulin gene variants among type II diabetic patients with fasting hyperinsulinemia (above 90 (μU/ml) and a fasting C-peptide to insulin molar ratio between 1.11 and 1.50. Alpha and beta alleles of the insulin gene were characterized by restriction analysis of polymerase chain reaction (PCR) products and direct sequencing. The more frequent occurrence of the alpha allele of the insulin gene within the control population as compared with a prevalence of the beta allele in the diabetic patients (P, 0.05) was observed. The beta allele, usually described as the rare allele, seems to be associated with the disease.
Similar content being viewed by others
References
Bell GI, Pictet RL, Rutter WJ, Cordell B, Tischer E, Goodman HH (1980) Sequence of the human insulin gene. Nature 284:26–32
Bell GI, Selby MJ, Rutter WJ (1982) The highly polymorphic region near the human insulin gene is composed of simply tandemly repeating sequences. Nature 295:31–35
Carroll RJ, Hammer RE, Chan SJ, Swift KH, Rubenstein AH, Steiner DF (1988) A mutant human proinsulin is secreted from islets of Langerhans in increased ammounts via unregulated pathway. Proc Natl Acad Sci USA 85:8943–8947
Chan SJ, Seino S, Gruppuso PA, Schwartz R, Steiner DF (1987) A mutation in B chain coding region is associated with impaired proinsulin conversion in a family with hyperinsulinemia. Proc Natl Acad Sci USA 784:2194–2197
Green PM, Bently DR, Hibashan DR, Nilsson RS, Giannelli IM (1989) Molecular pathology of haemophilia B. EMBO J 8:1067–1072
Haneda M, Chan SJ, Kwok SCM, Rubenstein AH, Steiner DF (1983) Studies on mutant human insulin genes: identification and sequence analysis of a gene coding [SerB24] insulin. Proc Natl Acad Sci USA 80:6366–6370
Haneda M, Polonsky K, Bergenstal EM, Jaspan JB, Shoelson SE, Blix PM, Chan SJ, Kwok SCM, Wishner WB, Zeidler A, Olefsky JM, Freidenburg G, Tager HS, Steiner DF, Rubenstein AH (1984) Familial hyperinsulinemia due to a structurally abnormal insulin. N Engl J Med 310:1288–1294
Hitman GA, Kambo PK, Viswanathan M, Mohan V (1991) An analysis of amplified insulin gene products in diabetes Indian origin. J Med Genet 28:97–99
Kwok SCM, Steiner DF, Rubenstein AH, Tager HS (1983) Identification of a point mutation in the human insulin gene giving rise to a structurally abnormal insulin (insulin Chicago). Diabetes 32:872–875
Leahy JL, Boyd AE (1993) Diabetes genes in non-insulin dependent diabetes melltius. N Engl J Med 328:56–57
Miller AD, Curran T, Verma IM (1984) C-fos protein can induce cellular transformation: a novel mechanism of activation of a cellular oncogene. Cell 36:51–60
Nanjo K, Sanke T, Kondo M, Nishimura S, Miyano M, Linuma J, Miyamura K, Inouye K, Given BD, Polonsky KS, Chan SJ, Tager HS, Steiner DF, Rubenstein AH (1988) Mutant insulin syndrome: identification of two families with [LeuA3] insulin and determination of its biological activity. Trans Assoc Am Physicians 99:132–142
Raghow R (1987) Regulation of messenger RNA turnover in eukaryotes. TIBS 12:358–360
Robbins DC, Blix PM, Rubenstein AH, Kanazawa Y, Kosaka K, Tager HS (1981) A human proinsulin variants at arginine 65. Nature 291:679–681
Ross J (1988) Messenger RNA turnover in eukaryotic cells. Mol Biol Med 5:1–14
Sanz N, Karam JH, Horita S, Bell GI (1986) Prevalence of insulingene mutations in non-insulin-dependent diabetes mellitus. N Engl J Med 314:1322–1325
Shoelson S, Haneda M, Blix P, Manjo A, Sanke T, Inouye K, Steiner DF, Rubenstein AH, Tager H (1983) Three mutant insulin in man. Nature 302:540–543
Tager H, Given B, Baldwin D, Mako M, Markese J, Rubenstein AH, Olefsky J, Kobayashi M, Kolterman O, Poucher R (1979) A structurally abnormal insulin causing human diabetes. Nature 281:122–125
Treisman R (1985) Transient accumulation of c-fos RNA following serum stimulation requires a conserved 5′ element and cfos 3′ sequences. Cell 42:889–902
Ullrich A, Dull TI, Gray A (1980) Genetic variation in the human insulin gene. Science 209:612–615
Vinik A, Bell GI (1988) Mutant insulin syndromes. Horm Metab Res 20:1–10
Weir GC (1993) A defective beta-cell glucose sensor as a cause of diabetes. N Engl J Med 238:729–731
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Horst-Sikorska, W., Zoll, B., Kwiatkowska, J. et al. Prevalence of beta allele of the insulin gene in type II diabetes mellitus. Hum Genet 93, 325–328 (1994). https://doi.org/10.1007/BF00212031
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00212031