medigraphic.com
ISSN 0185-6014 (Print)
Órgano oficial de difusión de la Federación Mexicana de Patología Clínica, AC y de la Asociación Latinoamericana de Patología Clínica/Medicina de Laboratorio

2001, Number 1

<< Back Next >>

Rev Mex Patol Clin Med Lab 2001; 48 (1)

Genotypes of adrenergic Beta-3 receptor in patients presenting non-proliferative diabetic retinopathy

Muñoz-Valle JF, Arturo Santos, Vázquez-Del Mercado M, Carrillo-Pérez C, Bastidas-Ramírez BE, Ruiz-Madrigal B, Panduro A

Language: Spanish
References: 18
Page: 7-16
PDF size: 158.66 Kb.


ABSTRACT

Introduction: Diabetic retinopathy (DR) is a frequent complication in diabetes mellitus. The risk factor to develop DR in patients with type 2 diabetes mellitus is greater in Mexican-Americans than non Hispanic whites, when the high risk factor in Mexican-American is unexplained. The Β3- adrenergic receptor (Β3-AR) is expressed in visceral fat and in brown and white adipose tissue in humans, where it is likely to regulate noradrenaline-induced changes in energy metabolism and thermogenesis. A missense mutation in codon 64 of the Β3-AR gene results in the replacement of tryptophan by arginine (Trp64Arg) in the first intracellular loop of the receptor protein. The Trp64Arg and Arg64Arg of the Β3-AR gene have been associated with high serum triglyceride and decreased HDL-cholesterol (HDL-c) levels in proliferative diabetic retinopathy patients. The objectives were to investigate the frequency and the effect of the Β3-AR polymorphism over the lipid profile in patients with non proliferative diabetic retinopathy (non-PDR) of the West of Mexico. Methods: We included 31 patients with non-PDR classified according to ETDRS Research Group. A group of 25 healthy subjects was studied. Fasting lipid profile was done in all the participants. Leukocyte genomic DNA isolation was performed from peripheral blood. Screening of Β3-AR gene polymorphic region (exon 1) was done by PCR-RFLP´s technique. The PCR product (248 bp) was digested using Mva I restriction enzyme. The PCR-RFLP´s patterns were identified by agarose-gel electrophoresis stained with ethidium bromide. Statistical analysis was performed using ANOVA with Tukey procedure and for qualitative variables χ2 and Pearson tests were used. Results: Highest levels of CT, TG, LDL-c and VLDL-c in patients with non-PDR compared to healthy subjects (p=0.03; p=0.0001; p=0.002; p=0.0001 respectively) was found. An association between Trp64Arg and Arg64Arg genotypes in non-PDR patients with Trp64Trp genotype of the healthy subjects (p=0.0197) was found. No association between Β3-AR genotype and lipid profile was observed. Conclusion: We suggest that Trp64Arg and Arg64Arg genotypes may contribute to develop of non-PDR. The increase of CT, TG, LDL-c and VLDL-c in non-PDR patients is independently of Β3-AR genotypes but dependently of type 2 diabetes mellitus.


REFERENCES

  1. De Blasi A. Beta-adrenergic receptors: structure, function and regulation. Drugs Exp Clin Res 1990; 16(3): 107-112.

  2. Garcia-Rubi E, Calles EJ. Insulin resistance and type 2 diabetes mellitus: Its relationship with the beta 3-adrenergic receptor. Arch Med Res 1999; 30(6): 459-464.

  3. Krief S, Lönnqvist F, Raimbault S et al. Tissue distribution of b-3 adrenergic receptor mRNA in man. J Clin Invest 1993; 91: 344-349.

  4. Strader CD, Sigal IS, Dixon RAF. Structural basis of b-3 adrenergic receptor function. FASEB J 1989; 3: 1825-1832.

  5. Strosberg AD. Structure and function of the b-3 adrenergic receptor. Ann Rev Pharmacol Toxicol 1997; 37: 421-450.

  6. Lönnqvist F, Thörne A, Nilsell K, Hoffstedt J, Arner P. A pathogenetic role of visceral fat b-3 adrenergic receptors in obesity. J Clin Invest 1995; 95: 1109-1116.

  7. Walden CC, Hegele RA. Apolipoprotein E in hyperlipidemia. Ann Intern Med 1994; 120: 1026-1036.

  8. Havel RJ, Kane JP. Introduction: structure and metabolism of plasma lipoproteins. In: Scriver CR ed. The metabolic basis of inherited diseases. 6th ed. New York- McGraw-Hill Information Services Co 1989; 1129: 38.

  9. Li WH, Tanimura M, Luu CC, Datta S, Chan L. The apolipoprotein multigene family, biosynthesis, structure, structure-function relationships, and evolution. J Lipid Res 1988; 29: 245-271.

  10. Walston J, Silver KD, Bogardus C, Knowler WC, Celi FS, Austin B, Manning B, Strosberg AD, Stern MP, Raben N et al. Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the b-3 adrenergic receptor gene. N Engl J Med 1995; 333: 343-347.

  11. Harris Maureen I, Klein R, Cowie CC, Rowland M, Byrd-Holt DD. Is the risk of diabetic retinopathy greater in non-hispanic blacks and Mexican Americans than in non-hispanic whites with type 2 diabetes?: A US population study. Diabetes Care 1998; 21(8): 1230-1235.

  12. Naoki S, Toshihide Y, Keiji Y, Yoshio N, Tunekazu U, Akinori K, Yasuto T, Motoharu K. b-3 adrenoreceptor gene polymorphism, a newly identified risk factor for proliferative retinopathy in NIDDM patients. Diabetes 1997; 46(10): 1633-1636.

  13. Xiang K, Jia W, Lu H, Zheng T, Lu J, Tang J, Ding W, Sun D, Li J. Effects of Trp64Arg mutation in the b-3 adrenergic receptor gene on body fat, plasma glucose level, lipid profile, insulin secretion and action in Chinese. Chung Hua I Chuan Hsueh Tsa Chih 1998; 15(6): 337-340.

  14. Clément K, Vaisse C, Manning B, Basdevant A, Guy-Grand B, Ruiz J, Silver KD, Shuldiner AR, Froguel P, Strosberg AD. Genetic variation in the b-3 adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. N Engl J Med 1995; 333: 352-354.

  15. Sakane N, Yoshida T, Umekawa T, Kondo M, Sakal Y, Takahashi T. b-3 adrenergic receptor polymorphism: a genetic marker for visceral fat obesity and the insulin resistance syndrome. Diabetologia 1997; 40: 200-204.

  16. Kurabayashi T, Carey DGP, Morrison NA. The b-3 adrenergic receptor gene Trp64Arg mutation is overrepresented in obese women. Diabetes 1996; 45: 1358-1363.

  17. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleid Acid Res 1988; 16: 1215-1219.

  18. Yoshida T, Sakane N, Umekawa T, Sakai M, Takahashi T, Kondo M. Mutation of b-3 adrenergic receptor gene and response to treatment of obesity. The Lancet 1995; 346: 1433-1434.




2020     |     www.medigraphic.com