Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population
Yıl: 2019 Cilt: 56 Sayı: 4 Sayfa Aralığı: 248 - 252 Metin Dili: İngilizce DOI: 10.29399/npa.23408 İndeks Tarihi: 02-09-2020
Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population
Öz: Introduction: Dopaminergic gene variants may affect nicotinedependence through their possible impact on the dopamine rewardpathway. The purpose of this study is to investigate the relationshipbetween the variable number tandem repeat (VNTR) variant in exon IIIof the Dopamine D4 receptor (DRD4) gene and genetic predisposition ofsmoking status in a Turkish population.Methods: We performed a study comparing 154 subjects as the smokergroup, and 111 subjects as the non-smoker group. Genotyping for theDRD4 VNTR variant was performed using a PCR method.Results: There was a significant difference between smoker and nonsmoker groups regarding the distribution of the alleles and genotypes ofthe DRD4 gene (p=0.000, p=0.000, respectively). The 2R allele was higherin the non-smoker group compare to the smoker group (p=0.000). Wefound that the 2/7 and 4/9 genotypes were more common in smokersthan non-smoker group (p=0.037, p=0.028, respectively) while 2/4genotype was more prevalent in non-smokers than smokers (p=0.000).When the number of repeat alleles (48 bp) are accepted as short (S) if sixor less, and as long (L) if seven or more, it was found that the frequency ofS/S genotype of the DRD4 VNTR variant was lower in the smoker groupand S/L genotype was higher in the smoker group (p=0.006, p=0.006,respectively). The subjects carrying the S/L genotype have a 2.25-foldincreased risk for smoking than a non-smoker.Conclusion: The results indicated that the subjects carrying DRD4exon III VNTR S/L genotype have a risk for smoking status in a Turkishpopulation.
Anahtar Kelime: Dopamin D4 Reseptör Gen Ekzon 3 VNTR Varyant Türk Populasyonunda Sigara İçme Durumunu Etkiler
Öz: Amaç: Dopaminerjik gen varyantları, dopamin ödül yolu üzerindeki olası etkileri yoluyla nikotin bağımlılığını etkileyebilir. Bu çalışmanın amacı, Dopamin D4 reseptör (DRD4) geni 3. ekzonundaki değişken sayılı bitişik tekrarlar (VNTR) ile Türk popülasyonundaki sigara içme durumuna yatkınlık arasındaki ilişkiyi araştırmaktır. Yöntem: Sigara içen grubu olarak 154 kişi ve sigara içmeyen grup olarak 111 kişiyi karşılaştıran bir çalışma yaptık. DRD4 VNTR varyant genotiplemesi PZR metodu kullanılarak yapıldı. Bulgular: Sigara içen ve sigara içmeyen gruplar arasında DRD4 gen genotip ve allel dağılımı açısından anlamlı fark vardı (p=0,000, p=0,000, sırasıyla). İki tekrarlı allel sigara içmeyen grupta sigara içen gruba kıyasla daha fazlaydı (p=0,000). Sigara içmeyen grupta 2/4 genotipi sigara içenlerden daha fazlayken (p=0,000), 2/7 ve 4/9 genotiplerinin sigara içen grupta sigara içmeyen gruptan daha fazla olduğunu (p=0,037, p=0,028, sırasıyla) bulduk. Kırk sekiz baz çiftlik tekrar alleleri altı tekrar veya daha kısa (K) ve 7 tekrar veya daha uzun (U) olarak kabul edildiğinde, DRD4 VNTR K/K genotipinin sigara içen grupta az ve K/U genotipinin sigara içen grupta fazla olduğu bulundu (sırasıyla, p=0,006, p=0,006). K/U genotipi taşıyan kişiler sigara içme açısından sigara içmeyenlere göre 2,25 kat yüksek riske sahipti. Sonuç: Sonuçlar, DRD4 ekzon 3 VNTR K/U genotip taşıyan kişilerin Türk toplumunda sigara içme riski taşıdığını göstermiştir.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- 1. Benowitz NL. Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol 2009;49:57–71. [CrossRef]
- 2. True WR, Heath AC, Scherrer JF, Waterman B, Goldberg J, Lin N, Eisen SA, Lyons MJ, Tsuang MT. Genetic and environmental contributions to smoking. Addiction 1997;92:1277–1287. [CrossRef]
- 3. Markou A. Neurobiology of nicotine dependence. Philos Trans R Soc Lond B Biol Sci 2008;363:3159–3168. [CrossRef]
- 4. Pidoplichko VI, DeBiasi M, Williams JT, Dani JA. Nicotine activates and desensitizes midbrain dopamine neurons. Nature 1997;390:401–404. [CrossRef]
- 5. Nestler EJ. Is there a common molecular pathway for addiction? Nat Neurosci 2005;8:1445–1449. [CrossRef]
- 6. Di Chiara G. Role of dopamine in the behavioural actions of nicotine related to addiction. Eur J Pharmacol 2000;393:295–314. [CrossRef]
- 7. Gelernter J, Liu X, Hesselbrock V, Page GP, Goddard A, Zhang H. Results of a genome-wide linkage scan: support for chromosomes 9 and 11 loci increasing risk for cigarette smoking. Am J Med Genet B Neuropsychiatr Genet 2004;128B:94–101. [CrossRef]
- 8. Ding YC, Chi HC, Grady DL, Morishima A, Kidd JR, Kidd KK, Flodman P, Spence MA, Schuck S, Swanson JM, Zhang YP, Moyzis RK. Evidence of positive selection acting at the human dopamine receptor D4 gene locus. Proc Natl Acad Sci USA 2002;99:309–314. [CrossRef]
- 9. Das D, Tan X, Easteal S. Effect of model choice in genetic association studies: DRD4 exon III VNTR and cigarette use in young adults. Am J Med Genet B Neuropsychiatr Genet 2011;156B:346–351. [CrossRef]
- 10. Hutchison KE, McGeary J, Smolen A, Bryan A, Swift RM. The DRD4 VNTR polymorphism moderates craving after alcohol consumption. Health Psychol 2002;21:139–146. [CrossRef]
- 11. Shao C, Li Y, Jiang K, Zhang D, Xu Y, Lin L, Wang Q, Zhao M, Jin L. Dopamine D4 receptor polymorphism modulates cue-elicited heroin craving in Chinese. Psychopharmacology (Berl) 2006;186:185–190. [CrossRef]
- 12. Babic M, Nedic G, Muck-Seler D, Borovecki F, Pivac N. Lack of association between dopamine receptor D4 variable numbers of tandem repeats gene polymorphism and smoking. Neurosci Lett 2012;520:67–70. [CrossRef]
- 13. Hutchison KE, LaChance H, Niaura R, Bryan A, Smolen A. The DRD4 VNTR polymorphism influences reactivity to smoking cues. J Abnorm Psychol 2002;111:134–143. [CrossRef]
- 14. Heatherton TF, Kozlowski LT, Frecker RC, Fagerström KO. The Fagerström test for nicotine dependence: A revision of the Fagerström tolerance questionnaire. Br J Addict 1991;86:1119–1127. [CrossRef]
- 15. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215. [CrossRef]
- 16. Lichter JB, Barr CL, Kennedy JL, Van Tol HH, Kidd KK, Livak KJ. A hypervariable segment in the human dopamine receptor D4 (DRD4) gene. Hum Mol Genet 1993;2:767–773. [CrossRef]
- 17. Stolerman IP, Shoaib M. The neurobiology of tobacco addiction. Trends Pharmacol Sci 1991;12:467–473. [CrossRef]
- 18. Benowitz NL. Nicotine Addiction. N Engl J Med 2010;362:2295–2303. [CrossRef]
- 19. Wonnacott S. Presynaptic nicotinic ACh receptors. Trends Neurosci 1997;20:92–98. [CrossRef]
- 20. Munafo M, Clark T, Johnstone E, Murphy M, Walton R. The genetic basis for smoking behavior: a systematic review and meta-analysis. Nicotine Tob Res 2004;6:583–597. [CrossRef]
- 21. Asghari V, Sanyal S, Buchwaldt S, Paterson A, Jovanovic V, Van Tol HH. Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. J Neurochem 1995;65:1157–1165. [CrossRef]
- 22. Oak JN, Oldenhof J, Van Tol HH. The dopamine D(4) receptor: one decade of research. Eur J Pharmacol 2000;405:303–327.
- 23. Rubinstein M, Phillips TJ, Bunzow JR, Falzone TL, Dziewczapolski G, Zhang G, Fang Y, Larson JL, McDougall JA, Chester JA, Saez C, Pugsley TA, Gershanik O, Low MJ, Grandy DK. Mice lacking dopamine D4 receptor are supersensitive to ethanol, cocaine, and methamphetamine. Cell 1997;90:991–1001. [CrossRef]
- 24. Van Tol HH, Wu CM, Guan HC, Ohara K, Bunzow JR, Civelli O, Kennedy J, Seeman P, Niznik HB, Jovanovic V. Multiple dopamine D4 receptor variants in the human population. Nature 1992;358:149–152. [CrossRef]
- 25. Brody AL, Mandelkern MA, Olmstead RE, Scheibal D, Hahn E, Shiraga S, Zamora-Paja E, Farahi J, Saxena S, London ED, McCracken JT. Gene variants of brain dopamine pathways and smoking-induced dopamine release in the ventral caudate/nucleus accumbens. Arch Gen Psychiatry 2006;63:808–816. [CrossRef]
| APA | UYSAL M, SEVER Ü, NURSAL A, GROUP Y, PEHLİVAN S (2019). Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population. , 248 - 252. 10.29399/npa.23408 |
| Chicago | UYSAL Mehmet Atilla,SEVER Ülgen,NURSAL Ayşe Feyda,GROUP Yedikule Smoking Cessation Study,PEHLİVAN Sacide Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population. (2019): 248 - 252. 10.29399/npa.23408 |
| MLA | UYSAL Mehmet Atilla,SEVER Ülgen,NURSAL Ayşe Feyda,GROUP Yedikule Smoking Cessation Study,PEHLİVAN Sacide Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population. , 2019, ss.248 - 252. 10.29399/npa.23408 |
| AMA | UYSAL M,SEVER Ü,NURSAL A,GROUP Y,PEHLİVAN S Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population. . 2019; 248 - 252. 10.29399/npa.23408 |
| Vancouver | UYSAL M,SEVER Ü,NURSAL A,GROUP Y,PEHLİVAN S Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population. . 2019; 248 - 252. 10.29399/npa.23408 |
| IEEE | UYSAL M,SEVER Ü,NURSAL A,GROUP Y,PEHLİVAN S "Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population." , ss.248 - 252, 2019. 10.29399/npa.23408 |
| ISNAD | UYSAL, Mehmet Atilla vd. "Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population". (2019), 248-252. https://doi.org/10.29399/npa.23408 |
| APA | UYSAL M, SEVER Ü, NURSAL A, GROUP Y, PEHLİVAN S (2019). Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population. Nöropsikiyatri Arşivi, 56(4), 248 - 252. 10.29399/npa.23408 |
| Chicago | UYSAL Mehmet Atilla,SEVER Ülgen,NURSAL Ayşe Feyda,GROUP Yedikule Smoking Cessation Study,PEHLİVAN Sacide Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population. Nöropsikiyatri Arşivi 56, no.4 (2019): 248 - 252. 10.29399/npa.23408 |
| MLA | UYSAL Mehmet Atilla,SEVER Ülgen,NURSAL Ayşe Feyda,GROUP Yedikule Smoking Cessation Study,PEHLİVAN Sacide Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population. Nöropsikiyatri Arşivi, vol.56, no.4, 2019, ss.248 - 252. 10.29399/npa.23408 |
| AMA | UYSAL M,SEVER Ü,NURSAL A,GROUP Y,PEHLİVAN S Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population. Nöropsikiyatri Arşivi. 2019; 56(4): 248 - 252. 10.29399/npa.23408 |
| Vancouver | UYSAL M,SEVER Ü,NURSAL A,GROUP Y,PEHLİVAN S Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population. Nöropsikiyatri Arşivi. 2019; 56(4): 248 - 252. 10.29399/npa.23408 |
| IEEE | UYSAL M,SEVER Ü,NURSAL A,GROUP Y,PEHLİVAN S "Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population." Nöropsikiyatri Arşivi, 56, ss.248 - 252, 2019. 10.29399/npa.23408 |
| ISNAD | UYSAL, Mehmet Atilla vd. "Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population". Nöropsikiyatri Arşivi 56/4 (2019), 248-252. https://doi.org/10.29399/npa.23408 |
