In order to analyze the association of CNR1(Cannabinoid receptor 1), GAD1(Glutamate decarboxylase 1), and BDNF(Brain-derived neurotrophic factor) polymorphisms with male heroin dependence in the Dai population in Yunnan Province, an eight-SNP co-amplification protocol was established to genotype on the SNaPshot platform. A case-control study was performed with 8 SNPs from CNR1, GAD1, and BDNF genes in 165 heroin-dependent males and 170 healthy males of the Dai population. Statistical analyses were conducted with SPSS17.0, Haploview4.2, PHASE2.1, and MDR software. We found that: (1) the genotype frequency of rs13306221 was significant in the case group (P<0.025); (2) the A allelic frequency of rs6265 was significantly higher in the case group; (3) the haplotypes of T-A-C, C-C-C, C-C-T, and T-C-C based on rs1978340-rs3791878-rs11542313 and haplotype A-G based on rs6265-rs13306221 were significant (P<0.05); (4) the haplotype frequencies of T-A-C, C-C-T, and A-G were significantly higher in the case group. These results indicate that the linkage between rs1978340 and rs3791878 in GAD1 has a strong association with heroin dependence. Furthermore, polymorphisms in CNR1 (rs1049353), GAD1 (rs1978340 and rs11542313), and BDNF (rs6265 and rs13306221) were associated with heroin dependence in the Yunnan Dai population, and individuals with the rs6265 A allele were more likely to be heroin dependent.
[1] V, Levran O, Proudnikov D, Nielsen DA, Kreek MJ. Search for genetic markers and functional variants involved in the development of opiate and cocaine addiction and treatment. Ann N Y Acad Sci , 2010, 1187(1): 184-207.
[2] MD, Burmeister M. New insights into the genetics of addiction. Nat Rev Genet , 2009, 10(4): 225-231.
[3] LD, Bobashev G, Morris RJ. Researching a local heroin market as a complex adaptive system. Am J Community Psychol , 2009, 44(3-4): 273-286.
[4] FJ. Mechanisms of opioid-induced overdose: experimental approach to clinical concerns. Ann Pharm Fr , 2009, 67(5): 353-359.
[5] AI. Addiction is a brain disease, and it matters. Science , 1997, 278(5335): 45-47.
[6] DM, Sellers EM. Addiction and the brain: the role of neurotransmitters in the cause and treatment of drug dependence. CMAJ , 2001, 164(6): 817-821.
[7] JA, Echeverry-Alzate V, Bühler KM. The genetic basis of the endocannabinoid system and drug addiction in humans. J Psychopharmacol , 2012, 26(1): 133-143.
[8] S, Griffon N, Bourdel MC, Olie JP, Poirier MF, Krebs MO. Schizophrenia and the cannabinoid receptor type 1 (CB1): association study using a single-base polymorphism in coding exon 1. Am J Med Genet , 2001, 105(8): 749-752.
[9] PW, Ishiguro H, Ohtsuki T, Hess J, Carillo F, Walther D, Onaivi ES, Arinami T, Uhl GR. Human cannabinoid receptor 1: 5' exons, candidate regulatory regions, polymorphisms, haplotypes and association with polysubstance abuse. Mol Psychiatry , 2004, 9(10): 916-931.
[10] T, Liu X, Zhu ZH, Zhao J, Hu X, Ball DM, Sham PC, Collier DA. No association between (AAT)n repeats in the cannabinoid receptor gene (CNR1) and heroin abuse in a Chinese population. Mol Psychiatry , 2000, 5(2): 128-130.
[11] D, Kroslak T, Sipe JC, Randesi M, Li D, Hamon S, Ho A, Ott J, Kreek MJ. Association of polymorphisms of the cannabinoid receptor (CNR1) and fatty acid amide hydrolase (FAAH) genes with heroin addiction: impact of long repeats of CNR1. Pharmacogenomics J , 2010, 10(3): 232-242.
[12] M, PastorI, dela Calle C, Barrio-Real L, Laso FJ, González-Sarmiento R. Cannabinoid receptor 1 gene is associated with alcohol dependence. Alcohol Clin Exp Res , 2012, 36(2): 267-271.
[13] TK, Bloch PJ, Ambrose-Lanci LM, Ferraro TN, Berrettini WH, Kampman KM, Dackis CA, Pettinati HM, O'Brien CP, Oslin DW, Lohoff FW. Further evidence for association of polymorphisms in the CNR1 gene with cocaine addiction: confirmation in an independent sample and meta-analysis. Addict Biol , 2013, 18(4): 702-708.
[14] LJ, Kranzler HR, Luo XG, Covault J, Gelernter J. CNR1 variation modulates risk for drug and alcohol dependence. Biological Psychiatry , 2007, 62(6): 616- 626.
[15] PH, Kalsi G, Prescott CA, Hodgkinson CA, Goldman D, Alexander J, van den Oord EJ, Chen X, Sullivan PF, Patterson DG, Walsh D, Kendler KS, Riley BP. Associations of glutamate decarboxylase genes with initial sensitivity and age-at-onset of alcohol dependence in the Irish Affected Sib Pair Study of Alcohol Dependence. Drug Alcohol Depend , 2009, 101(1-2): 80-87.
[16] C, Tucci M, Forza G, Barzon L, Palu G, Ferrara SD. Alcohol dependence and glutamate decarboxylase gene polymorphisms in an Italian male population. Alcohol , 2010, 44(5): 407-413.
[17] O, Londono D, O'Hara K, Randesi M, Rotrosen J, Casadonte P, Linzy S, Ott J, Adelson M, Kreek MJ. Heroin addiction in African Americans: a hypothesis-driven association study. Genes Brain Behav , 2009, 8(5): 531-540.
[18] W, Zhu YS, Li SB. Polymorphisms in the glutamate decarboxylase 1 gene associated with heroin dependence. BiochemBiophys Res Commun , 2012, 422(1): 91-96.
[19] BS. BDNF rs6265 polymorphism and drug addiction: a systematic review and meta-analysis. Pharmacogenomics, 2013, 14(16): 2055-2065.
[20] C, Lan J, Wang Y, Song M, Gao X, Ran L, Moira S, Wang W. Influence of brain-derived neurotrophic factor genetic polymorphisms on the ages of onset for heroin
