Association between two µ-opioid receptor gene (OPRM1) haplotype blocks and drug or alcohol dependence

• Published in: Human molecular genetics 2006-03, Vol.15 (6), p.807-819
• Main Authors: Zhang, Huiping, Luo, Xingguang, Kranzler, Henry R., Lappalainen, Jaakko, Yang, Bao-Zhu, Krupitsky, Evgeny, Zvartau, Edwin, Gelernter, Joel
• Format: Article
• Language: English
• Subjects: Adult; Alcoholism - genetics; Alleles; Case-Control Studies; Female; Genotype; Haplotypes; Humans; Male; Polymorphism, Single Nucleotide; Receptors, Opioid, mu - genetics; Regression Analysis; Risk Factors; Substance-Related Disorders - genetics
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddl024

We examined 13 single nucleotide polymorphisms (SNPs) spanning the coding region of the µ-opioid receptor gene (OPRM1), among 382 European Americans (EAs) affected with substance dependence [alcohol dependence (AD) and/or drug dependence (DD)] and 338 EA healthy controls. These SNPs delineated two haplotype blocks. Genotype distributions for all SNPs were in Hardy–Weinberg equilibrium (HWE) in controls, but in cases, four SNPs in Block I and three SNPs in Block II showed deviation from HWE. Significant differences were found between cases and controls in allele and/or genotype frequencies for six SNPs in Block I and two SNPs in Block II. Association of SNP4 in Block I with DD (allele: P=0.004), SNP5 in Block I with AD and DD (allele: P≤0.005 for both) and two SNPs in Block II with AD (SNP11 genotype: P=0.002; SNP12 genotype: P=0.001) were significant after correction for multiple testing. Frequency distributions of haplotypes (constructed by five tag SNPs) differed significantly for cases and controls (P