Dopamin Reseptör 2 (DRD2) Gen Polimorfizmlerinin Obezite Hastalığına Yakalanma Riski ile İlişkisi

Amaç: Obezite genel tıbbi hastalıkların yanı sıra sosyal ve psikolojik sorunlar için de oldukça önemli risk etkenidir. Obezitenin mekanizması tam olarak bilinmemekle birlikte sosyal, kültürel, psikolojik, metabolik ve genetik faktörlerin önemli roller oynadığına dair kuvvetli deliller vardır. Dopaminerjik sistemin, beyindeki ödüllendirme ve pekiştirici mekanizmalar üzerindeki etkileri göz önüne alındığında, obeziteye yatkınlık açısından önemli bir genetik aday olduğu bildirilmektedir. Bu çalışmada dopamin D2 reseptör geninin Taq1 A ve Taq1 B polimorfizmleri ile obezite hastalığına yakalanma riski arasında olası ilişki araştırıldı. Yöntem: 140 hasta ve 120 sağlıklı gönüllünün venöz kanlarından DNA izole edildi. Polimorfizmlerin tespit edilmesinde polimeraz zincir reaksiyonu - restriksiyon parça uzunluk polimorfizmi yöntemi kullanıldı. Bulgular: DRD2 Taq1 A polimorfizmi A1-allel sıklığı (p<0.05) obez hastalarda anlamlı olarak daha yüksekti. Ancak, obez hastalar ve kontrol grubu (p>0.05) arasındaki DRD2 Taq1 B polimorfizmi açısından anlamlı bir fark yoktu.Sonuç: Sonuçlarımız DRD2 Taq1 A polimorfizminde A1 alleli varlığının obezite için bir risk faktörü olabileceğini düşündürmektedir.
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  • Antipatis VJ, Gill TP. Obesity as a global problem. In: Bjömtorp P, editor. International Textbook of Obesity. 1. Baskı, Electronic. John Wiley and Sons Ltd; 2001:3-23.
  • Satman İ, SengülAM, Uygur S, Satman I, Yılmaz T, Sengül A, Salman S, Salman F, Uygur S, Bastar I, Tütüncü Y, Sargın M, Dinççag N, Karsidag K, Kalaça S, Özcan C, King H, The TURDEP Group. Population based study of diabetes and risk characteristics in Turkey: results of the Turkish diabetes epidemiology study (TURDEP). Diabetes Care 2002;25(9): 1551-56.
  • Taşan E. Identification, evaluation and epidemiology of obesity. JlntMed Sci 2005;1(37):1-4.
  • Hellerstein MK, Parks EJ. Obesity and Overweight. In: Gardner DG, Shobeck D, editors. Greenspan's Basic and Clinical Endocrinology. 8. Baskı, New York: McGrawHill; 2007:796-816.
  • Beales P, Kopelman P, Vijayaraghavan S, Hitman GA. The molecular genetics of obesity. In: Bray G, Ryan DH, editors. Molecular Genetic Aspects of Obesity, Pennington Center Nutrition Series. 1. Baskı, Baton Rouge, LA: Louisiana State Press; 1996:534-45.
  • Small DM, Jones-Gotman M, Dagher A. Feeding-induced dopamine release in dorsal striatum correlates with meal pleasantness ratings in healthy human volunteers. Neuroi mage 2003; 19(4): 1709-15.
  • De Leon J, Diaz FJ, Josiassen RC, Cooper TB, Simpson GM. Weight gain during a double-blind multidosage clozapine study. J Clin Psychopharmacol 2007;27(l):22-7.
  • Gingrich JA, Caron MG. Recent advances in the molecular biology of dopamine receptors. Annu Rev Neurosci 1993; 16:299-321.
  • Blum K, Sheridan PJ, Wood RC, Braverman ER, Chen TJ, Cull JG, Comings DE. The D2 dopamine receptor gene as a determinant of reward deficiency syndrome. JR Soc Med 1996;89(7):396-400.
  • Volkow ND, Wang GJ, Telang F, Fowler JS, Thanos PK, Logan J, AlexoffD, Ding YS, Wong C, Ma Y, Pradhan K. Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contribu ting factors. Neuroimage 2008;42(4):1537-43.
  • Wang G J, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, Netusil N, Fowler JS. Brain dopamine and obesity. Lancet 2001;357(9253):354-7.
  • Fetissov SO, Meguid MM, Sato T, Zhang LH. Expression of dopaminergic receptors in the hypothalamus of lean and obese Zucker rats and food intake. Am J Physiol Regul Integr Comp Physiol 2002;283(4): R905-10.
  • Orosco M, Rouch C, Nicolaidis S. Rostromedial hypothalamic monoamine changes in response to intravenous infusions of insulin and glucose in freely feeding obese Zucker rats: a microdialysis study. Appetite 1996;26(l):l-20.
  • Wang GJ, Volkow ND, Fowler JS. The role of dopamine in motivation for food in humans: implications for obesity. Expert Opin Ther Targets 2002;6(5): 601-9.
  • Turner E, Ewing J, Shilling P, Smith TL, Irwin M, Schuckit M, Kelsoe JR. Lack of association between an RFLP near the D2 dopamine receptor gene and severe alcoholism. Biol Psychiatry 1992;31(3):285-90.
  • Grandy DK, Litt M, Allen L, Bunzow JR, Marchionni M, Makam H, Reed L, Magenis RE, Civelli O. The human dopamine D2 receptor gene is located on chromosome 11 at q22-q23 and identifies a Taql RFLP. Am J Hum Genet 1989;45(5):778-85.
  • Comings DE, Flanagan SD, Dietz G, Muhleman D, Knell E, Gy sin R. The dopamine D2 receptor (DRD2) as a major gene in obesity and height. Biochem Med Metab Biol 1993;50(2): 176-85.
  • Hauge XY, Grandy DK, Eubanks JH, Evans GA, Civelli O, Litt M. Detection and characterization of additional DNA polymorphisms in the dopamine D2 receptor gene. Genomics 1991;10(3):527-30.
  • Noble EP, Blum K, Ritchie T, Montgomery A, Sheridan PJ. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch Gen Psychiatry 1991;48(7):648-54.
  • Castiglione CM, Deinard AS, Speed WC, Sirugo G, Rosenbaum HC, Zhang Y, Grandy DK, Grigorenko EL, Bonne-Tamir B, Pakstis AJ. Evolution of haplotypes at the DRD2 locus. Am JHum Genet 1995;57(6):1445-56.
  • Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extraction DNA from human nucleated cells. Nucleic Acids Res 1988; 16(3): 1215.
  • Oliveri RL, Annesi G, Zappia M, Civitelli D, De Marco EV, Pasqua AA, Annesi F, Spadafora P, Gambardella A, Nicoletti G, Branca D, Caracciolo M, Aguglia U, Quattrone A. The dopamine D2 receptor gene is a susceptibility locus for Parkinson's disease. Mov Disord 2000;15(1):127-31.
  • Spitz MR, Detry MA, Pillow P, Hu Y, Amos CI, Ki Hong W, Wu X. Variant alleles of the D2 dopamine receptor gene and obesity. Nutrition Research 2000;20(3):371-80.
  • Blum K, Braverman ER, Wood RC, Gill J, Li C, Chen TJ, Taub M, Montgomery A, Sheridan PJ, Cull JG. Increased prevalence of the TaqI A1 allele of the dopamine receptor gene (DRD2) in obesity with comorbid substance use disorder: a preliminary report. Pharmacogenetics 1996; 6(4):297-305.
  • Noble EP, Noble RE, Ritchie T, Syndulko K, Bohlman MC, Noble LA, Zhang Y, Sparkes RS, Grandy DK. D2 dopamine receptor gene and obesity. IntJ Eat Disord 1994; 15(3):205-17.
  • Nisoli E, Brunani A, Borgomainerio E, Tonello C, Dioni L, Briscini L, Redaelli G, Molinari E, Cavagnini F, Carruba MO. D2 dopamine receptor (DRD2) gene TaqlA polymorphism and the eating-related psychological traits in eating disorders (anorexia nervosa and bulimia) and obesity. Eat Weight Disord 2007;12(2):91-6.
  • Hardman CA, Rogers PJ, Timpson NJ, Munafö MR. Lack of association between DRD2 and OPRM1 genotypes and adiposity. Int J Obes (Lond) 2014;38(5):730-6.
  • Col Araz N, Nacak M, Oguzkan Balcı S, Benlier N, Araz M, Pehlivan S, Balat A, Aynacioglu AS. Childhood obesity and the role of dopamine D2 receptor and cannabinoid receptor-1 gene polymorphisms. Genet Test Mol Biontar kers 2012;16(12):1408-12.
  • Ergun MA, Karaoguz MY, Koc A, Çamurdan O, Bideci A, Yazici AC, Cinaz P. The apolipoprotein E gene and TaqlA polymorphisms in childhood obesity. Genet Test Mol Bio markers 2010;14(3):343-5.