Association of Specific Haplotypes of D2 Dopamine ReceptorGene With Vulnerability to Heroin Dependence in 2 Distinct Populations

• DOI: 10.1001/archpsyc.61.6.597
• Publication Date: 2004-06-07T20:57:27Z
• Authors: Ke Xu; Dirk Lichtermann; Robert H. Lipsky; Petra Franke; Xiehe Liu; Ying Hu; Liping Cao; Sibylle G. Schwab; Dieter B. Wildenauer; Claiton H. D. Bau; Erica Ferro; Will Astor; Thembi Finch; Jeanietta Terry; Julie Taubman; Wolfgang Maier; David Goldman
• Keywords: Linkage Disequilibrium; Population stratification

<h3>Context</h3> Dopamine receptor–mediated pathways play critical roles in the mechanism of addiction. However, associations D₂dopamine receptor gene (<i>DRD2)</i>with substance abuse are controversial. <h3>Objective</h3> To determine whether susceptibility sites resided at<i>DRD2.</i> <h3>Design</h3> Haplotype-based case-control analysis 2 distinct populations using 10 single nucleotide polymorphisms (SNPs) with heroin dependence. <h3>Setting</h3> Universities Mainz and Bonn, Germany, 3 local hospitals southwestern China. <h3>Patients</h3> Cases control subjects recruited from China (486 cases, 313 controls) Germany (471 192 controls). <h3>Interventions</h3> Genotyping for SNPs by 5′-exonuclease fluorescence assays. The D′ value linkage disequilibrium haplotypes were generated expectation-maximization algorithm. <h3>Main Outcome Measures</h3> Genotype, allele, haplotype frequencies compared between cases controls χ²tests constructed each population. An additional 32 randomly distributed genome genotyped detecting population admixture populations. <h3>Results</h3> A block 25.8 kilobases (kb) was defined 8 extending from<i>SNP3</i>(<i>TaqIB</i>) at 5′ end to<i>SNP10</i>site (<i>TaqIA</i>) located kb distal to 3′ gene. Within this block, specific cluster (carrying<i>TaqIB1</i>allele) associated a high risk dependence Chinese patients (<i>P</i>= 1.425 × 10⁻²²; odds ratio, 52.80; 95% confidence interval, 7.290-382.5 8-SNP analysis). putative recombination "hot spot" found near<i>SNP6</i>(intron 6 ins/del G), creating new daughter that lower Germans 1.94 10⁻¹¹for There no evidence stratification either <h3>Conclusions</h3> These results strongly support role of<i>DRD2</i>as low Germans.