PDF herunterladen
Exp Clin Endocrinol Diabetes 2007; 115(5): 327-330
DOI: 10.1055/s-2007-967084
Short Communication

© J. A. Barth Verlag in Georg Thieme Verlag KG · Stuttgart · New York

An Insertion/Deletion Polymorphism in the Alpha2B Adrenoceptor Gene is Associated with Peripheral Neuropathy in Patients with Type 2 Diabetes Mellitus

N. Papanas 1 , K. Papatheodorou 1 , D. Papazoglou 1 , S. Kotsiou 1 , D. Christakidis 2 , E. Maltezos 1
  • 1Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Dragana, Alexandroupolis, Greece
  • 2Diabetic Department, University Hospital of Alexandroupolis, Dragana, Alexandroupolis, Greece
Weitere Informationen

Publikationsverlauf

received 11. 12. 2006 first decision 9. 01. 2007

accepted 9. 01. 2007

Publikationsdatum:
21. Mai 2007 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Alpha2B adrenoceptor (alpha2B-AR) mediates a variety of functions in humans. An insertion/deletion (I/D) polymorphism of the alpha2B-AR gene located on chromosome 2 has been described. The aim of the present study was to investigate the potential association between alpha2B gene I/D polymorphism and peripheral neuropathy in Greek patients with type 2 diabetes mellitus. The study included 130 patients (70 men) with diabetic neuropathy (group A) and 60 patients (34 men) without diabetic neuropathy (group B). There was no difference in age, gender and diabetes duration between the groups. Diabetic neuropathy was diagnosed by clinical examination using the Diabetic Neuropathy Index (DNI). Genotyping of I/D polymorphism was performed by PCR. Frequency of the D allele was significantly higher (p=0.001) in group A (26.9%) as compared to group B (11.7%). DNI score differed significantly (p=0.001) between the three genotype groups (I/I, I/D, D/D). It was significantly higher (p=0.04) in patients with I/D (3.7±1) than in those with I/I (2.5±0.9) and significantly higher (p=0.001) in patients with D/D (5.6±1.3) than in those with I/D (3.7±1)

Conclusions: Patients with neuropathy exhibit a significantly higher frequency of the D allele in comparison to those without neuropathy. Presence of the D allele is also associated with a higher neuropathic score. These results provide evidence for an association of the D allele with both presence and severity of neuropathy in patients with type 2 diabetes mellitus.

Key words

adrenoceptor - diabetes mellitus - diabetic neuropathy - polymorphism

References

  • 1 Bax G, Fagherazzi C, Piarulli F, Nicolucci A, Fedele D. Reproducibility of Michigan Neuropathy Screening Instrument (MNSI).  Diabetes Care. 1996;  19 904-905
    PubMedSuche in Google Scholar
  • 2 Bedlack RS, Edelman D, Gibbs III JW, Kelling D, Strittmatter W, Saunders AM. et al . APOE genotype is risk factor for neuropathy severity in diabetic patients.  Neurology. 2003;  60 1022-1024
    PubMedSuche in Google Scholar
  • 3 Boulton AJM, Kirsner RS, Vileikyte L. Neuropathic diabetic foot ulcers.  N Engl J Med. 2004;  351 48-55
    CrossrefPubMedSuche in Google Scholar
  • 4 Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, Malik RA, Maser RE, Sosenko JM, Ziegler D. American Diabetes Association . Diabetic neuropathies: a statement by the American Diabetes Association.  Diabetes Care. 2005;  28 956-962
    CrossrefPubMedSuche in Google Scholar
  • 5 Duby JJ, Campbell RK, Setter SM, White JR, Rasmussen KA. Diabetic neuropathy: an intensive review.  Am J Health Syst Pharm. 2004;  61 160-173
    PubMedSuche in Google Scholar
  • 6 Edmonds ME. The diabetic foot, 2003.  Diabetes Metal Res Rev. 2004;  20 ((Suppl 1)) S9-S12
    PubMedSuche in Google Scholar
  • 7 Fedele D, Comi G, Coscelli C, Cucinotta D, Feldman EL, Ghirlanda G. et al . A multicenter study on the prevalence of diabetic neuropathy in Italy.  Diabetes Care. 1997;  20 836-843
    CrossrefPubMedSuche in Google Scholar
  • 8 Feldman EL, Stevens MJ, Thomas PK, Brown MB, Canal L, Greene DA. A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy.  Diabetes Care. 1994;  17 1281-1289
    CrossrefPubMedSuche in Google Scholar
  • 9 Heinonen P, Koulu M, Pesonen U, Karvonen MK, Rissanen A, Laakso M. et al . Identification of a three-amino acid deletion in the alpha2B-adrenergic receptor that is associated with reduced basal metabolic rate in obese subjects.  J Clin Endocrinol Metab. 1999;  84 2429-2433
    CrossrefPubMedSuche in Google Scholar
  • 10 Lomasney JW, Lorenz W, Allen LF, King K, Regan JW, Yang-Feng TL. et al . Expansion of the alpha 2-adrenergic receptor family: cloning and characterization of a human alpha 2-adrenergic receptor subtype, the gene for which is located on chromosome 2.  Proc Natl Acad Sci USA. 1990;  87 5094-5098
    CrossrefPubMedSuche in Google Scholar
  • 11 Papanas N, Papatheodorou K, Christakidis, Papazoglou D, Giassakis G, Piperidou H. et al . Evaluation of a new indicator test for sudomotor function (Neuropad®) in the diagnosis of peripheral neuropathy in type 2 diabetic patients.  Exp Clin Endocrinol Diabetes. 2005;  113 195-198
    Thieme ConnectPubMedSuche in Google Scholar
  • 12 Papazoglou D, Papanas N, Papatheodorou K, Kotsiou S, Christakidis D, Maltezos E. An insertion/deletion polymorphism in the alpha2B adrenoceptor gene is associated with age at onset of type 2 diabetes mellitus.  Exp Clin Endocronol Diabetes. 2006;  114 424-427
    PubMedSuche in Google Scholar
  • 13 Quattrini C, Jeziorska M, Malik RA. Small fiber neuropathy in diabetes: clinical consequence and assessment.  Int J Low Extrem Wounds. 2004;  3 16-21
    CrossrefPubMedSuche in Google Scholar
  • 14 Raccah D, Coste TC, Vague P. Genetics of diabetic complications: peripheral neuropathy.  Ann Endocrinol (Paris). 2004;  65 ((Suppl 1)) S5-S9
    PubMedSuche in Google Scholar
  • 15 Rudofsky Jr G, Schroedter A, Schlotterer A, Voron’ko OE, Schlimme M, Tafel J. et al . Functional polymorphisms of UCP2 and UCP3 are associated with a reduced prevalence of diabetic neuropathy in patients with type 1 diabetes.  Diabetes Care. 2006;  29 89-94
    CrossrefPubMedSuche in Google Scholar
  • 16 Shaw JE, Gries FA, Ziegler D. Epidemiology of diabetic neuropathy. In: Gries FA, Low PA, Ziegler D (Eds) Textbook of diabetic neuropathy. New York: Thieme Verlag 2003: 64-79
    Suche in Google Scholar
  • 17 Siitonen N, Lindström J, Eriksson J, Valle TT, Hämäläinen H, Ilanne-Parikka P. et al . Association between a deletion/insertion polymorphism in the alpha2B-adrenergic receptor gene and insulin secretion and Type 2 diabetes. The Finnish Diabetes Prevention Study.  Diabetologia. 2004;  47 1416-1424
    PubMedSuche in Google Scholar
  • 18 Sima AA. New insights into the metabolic and molecular basis for diabetic neuropathy.  Cell Mol Life Sci. 2003;  60 2445-2464
    CrossrefPubMedSuche in Google Scholar
  • 19 Singleton JR, Smith AG, Bromberg MB. Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy.  Diabetes Care. 2001;  24 1448-1453
    CrossrefPubMedSuche in Google Scholar
  • 20 Sivenius K, Lindi V, Niskanen L, Laakso M, Uusitupa M. Effect of a three-amino acid deletion in the alpha2B-adrenergic receptor gene on long-term body weight change in Finnish non-diabetic and type 2 diabetic subjects.  Int J Obes Relat Metab Disord. 2001;  25 1609-1614
    CrossrefPubMedSuche in Google Scholar
  • 21 Sivenius K, Niskanen L, Laakso M, Uusitupa M. A deletion in the alpha2B-adrenergic receptor gene and autonomic nervous function in central obesity.  Obes Res. 2003;  11 962-970
    PubMedSuche in Google Scholar
  • 22 Sivenius K, Pihlajamaki J, Partanen J, Niskanen L, Laakso M, Uusitupa M. Aldose reductase gene polymorphisms and peripheral nerve function in patients with type 2 diabetes.  Diabetes Care. 2004;  27 2021-2026
    CrossrefPubMedSuche in Google Scholar
  • 23 Snapir A, Heinonen P, Tuomalainen TP, Alhopuro P, Karvonen MK, Lakka TA. et al . An insertion/deletion polymorphism in the alpha2B-adrenergic receptor gene is a novel genetic risk factor for acute coronary events.  J Am Coll Cardiol. 2001;  37 1516-1522
    CrossrefPubMedSuche in Google Scholar
  • 24 Sugimoto K, Murakawa Y, Sima AA. Diabetic neuropathy-a continuing enigma.  Diabetes Metab Res Rev. 2000;  16 408-433
    CrossrefPubMedSuche in Google Scholar
  • 25 Sumner CJ, Sheth S, Griffin JW, Cornblath DR, Polydefkis M. The spectrum of neuropathy in diabetes and impaired glucose tolerance.  Neurology. 2003;  60 108-111
    CrossrefPubMedSuche in Google Scholar
  • 26 Suzuki N, Matsunaga T, Nagasumi K, Yamamura T, Shihara N, Moritani T. et al . Alpha(2B)-adrenergic receptor deletion polymorphism associates with autonomic nervous system activity in young healthy Japanese.  J Clin Endocrinol Metab. 2003;  88 1184-1187
    CrossrefPubMedSuche in Google Scholar
  • 27 Ueno LM, Frazzatto ES, Batalha LT, Trombetta IC, do Socorro Brasileiro M, Irigoyen C. et al . Alpha2B-adrenergic receptor deletionpolymorphism andcardiac autonomic nervous system responses to exercise in obese women.  Int J Obes (Lond). 2006;  30 214-220
    CrossrefPubMedSuche in Google Scholar
  • 28 Veves A, Manes C, Murray HJ, Young MJ, Boulton AJ. Painful neuropathy and foot ulceration in diabetic patients.  Diabetes Care. 1993;  16 1187-1189
    CrossrefPubMedSuche in Google Scholar
  • 29 Zhou Z, Hoke A, Cornblath DR, Griffin JW, Polydefkis M. APOE ε4 is not a susceptibility gene in idiopathic or diabetic sensory neuropathy.  Neurology. 2005;  64 139-141
    PubMedSuche in Google Scholar

Correspondence

N. Papanas

Ethnikis Antistasis 44

Alexandroupolis 68100

Greece

Telefon: +30/255/108 49 72

Fax: +30/255/107 47 23

eMail: papanasnikos@yahoo.gr