PMID- 28692418 OWN - NLM STAT- MEDLINE DCOM- 20180417 LR - 20220408 IS - 1557-8100 (Electronic) IS - 1536-2310 (Linking) VI - 21 IP - 7 DP - 2017 Jul TI - Contribution of Genetic Polymorphisms and Haplotypes in DRD2, BDNF, and Opioid Receptors to Heroin Dependence and Endophenotypes Among the Han Chinese. PG - 404-412 LID - 10.1089/omi.2017.0057 [doi] AB - Heroin and drug dependence are major contributors to global health burden worldwide, but their underlying mechanisms remain elusive and may vary from population to population. Reward- and memory-related candidate genes dopamine D2 receptor (DRD2) and brain-derived neurotrophic factor (BDNF), as well as the opioid receptor genes (OPRM1, OPRD1, and OPRK1), have been implicated in drug dependence, but relatively little is known on their contributions to heroin dependence in populations worldwide. Hence, we evaluated the contributions of the above five candidate genes in heroin dependence and several important related endophenotypes (the onset age of heroin use and subjective response to first heroin use), at single single-nucleotide polymorphism as well as haplotype levels, in a Han Chinese population sample. We genotyped 546 unrelated and heroin-dependent subjects for the candidate genes noted, and 228 sex- and age-matched unrelated controls. The G allele of rs4654327 (OPRD1), DRD2 haplotype block CCGCCGTT (rs6277-rs1076560-rs2283265-rs2734833-rs2075652-rs1079596-rs4436578-rs11214607), and OPRD1 haplotypes TACG (rs6669447-rs2236857-rs508448-rs4654327), CG (rs508448-rs4654327), and TG (rs6669447-rs4654327) were significantly associated with heroin dependence phenotype. Homozygotes AA at rs6265 (BDNF), TT at rs16917234 (BDNF), and CC at rs508448 (OPRD1) also appeared as risk factors for the endophenotype earlier age of onset for heroin use. Two OPRM1 haplotypes, AG (rs1799971-rs1381376) and AT (rs1799971-rs3778151), were observed as potential protective factors. These emerging findings contribute to the literature on genetic biomarkers of drug dependence and related endophenotypes, and call for replication in independent population. FAU - Gao, Xuan AU - Gao X AD - 1 Savaid Medical School, University of Chinese Academy of Sciences , Beijing, P.R. China . FAU - Wang, Youxin AU - Wang Y AD - 2 School of Public Health, Capital Medical University , Beijing, P.R. China . FAU - Lang, Minglin AU - Lang M AD - 3 College of Life Science, University of Chinese Academy of Sciences , Beijing, P.R. China . FAU - Yuan, Li AU - Yuan L AD - 1 Savaid Medical School, University of Chinese Academy of Sciences , Beijing, P.R. China . FAU - Reece, Albert Stuart AU - Reece AS AD - 4 Divison of Psychiatry, University of Western Australia , Crawley, Australia . FAU - Wang, Wei AU - Wang W AD - 2 School of Public Health, Capital Medical University , Beijing, P.R. China . AD - 5 School of Medical and Health Sciences, Edith Cowan University , Perth, Australia . LA - eng PT - Journal Article PL - United States TA - OMICS JT - Omics : a journal of integrative biology JID - 101131135 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (OPRD1 protein, human) RN - 0 (OPRM1 protein, human) RN - 0 (Receptors, Dopamine D2) RN - 0 (Receptors, Opioid) RN - 0 (Receptors, Opioid, delta) RN - 0 (Receptors, Opioid, mu) RN - 7171WSG8A2 (BDNF protein, human) SB - IM MH - Alleles MH - Brain-Derived Neurotrophic Factor/*genetics MH - Female MH - Gene Frequency/genetics MH - Genetic Association Studies MH - Genetic Predisposition to Disease/genetics MH - Genotype MH - Haplotypes/genetics MH - Humans MH - Linkage Disequilibrium/genetics MH - Male MH - Polymorphism, Genetic/genetics MH - Polymorphism, Single Nucleotide/*genetics MH - Receptors, Dopamine D2/*genetics MH - Receptors, Opioid/*genetics MH - Receptors, Opioid, delta/genetics MH - Receptors, Opioid, mu/genetics OTO - NOTNLM OT - BDNF OT - DRD2 OT - Han Chinese OT - OPRD1 OT - OPRK1 OT - OPRM1 OT - genetic association study EDAT- 2017/07/12 06:00 MHDA- 2018/04/18 06:00 CRDT- 2017/07/11 06:00 PHST- 2017/07/11 06:00 [entrez] PHST- 2017/07/12 06:00 [pubmed] PHST- 2018/04/18 06:00 [medline] AID - 10.1089/omi.2017.0057 [doi] PST - ppublish SO - OMICS. 2017 Jul;21(7):404-412. doi: 10.1089/omi.2017.0057.