Human population genetic structure detected by pain-related mu opioid receptor gene polymorphisms

Abstract

Several single nucleotide polymorphisms (SNPs) in the Mu Opioid Receptor gene (OPRM1) have been identified and associated with a wide variety of clinical phenotypes related both to pain sensitivity and analgesic requirements. The A118G and other potentially functional OPRM1 SNPs show significant differences in their allele distributions among populations. However, they have not been properly addressed in a population genetic analysis. Population stratification could lead to erroneous conclusions when they are not taken into account in association studies. The aim of our study was to analyze OPRM1 SNP variability by comparing population samples of the International Hap Map database and to analyze a new population sample from the city of Corrientes, Argentina. The results confirm that OPRM1 SNP variability differs among human populations and displays a clear ancestry genetic structure, with three population clusters: Africa, Asia, and Europe-America.

Genetic Differentiation of North-East Argentina Populations Based on 30 Binary X Chromosome Markers

“…In this work we analyzed the differentiation among the populations from three different north-east localities from Argentina: the two capital cities of Posadas and Corrientes, and the city of Eldorado. Previous studies include autosomal SNPs within coding regions for Corrientes city (Lopez-Soto and Catanesi, 2015 ) and STRs of X chromosome for Corrientes and Posadas (Glesmann et al, 2011 ). The report on autosomal SNPs showed clear differences in the comparison of Corrientes to other populations of the world, while the report on X-chromosome STRs presented certain differentiation between Corrientes and Posadas (Di Santo et al, 2015 ).…”

The OPRM1 A118G polymorphism modulates the descending pain modulatory system for individual pain experience in young women with primary dysmenorrhea

“…There are several explanations for these inconsistencies in the existing literature, including differences in sex proportion (sex by genotype interaction emerges for heat pain37), pain modalities (neither electrical3 nor pressure37 pain stimulation), and ethnicity (Asians are different from Caucasians in the G allele variability38 and in the phenotype of the OPRM1 A118G polymorphism39). As the penetrance of genes can be greater at the level of brain biology than at the level of behavior40, neuroimaging bridges the mechanistic gap between gene and behavior41.…”

Genetic variation in the behavioral effects of buprenorphine in female mice derived from a murine model of the OPRM1 A118G polymorphism

“…The A118G SNP corresponds to an amino acid substitution of asparagine (N) to aspartic acid (D) at position 40 in the N-glycosylation site of the receptor, resulting in protein instability and reduced expression of MORs at the cell surface (Huang et al, 2012; Mague et al, 2009; Oertel et al, 2012; Zhang et al, 2015). Subjective pain scores are noticeably higher in carriers of the G allele and they require significantly larger doses of opioid analgesics to alleviate their pain (Baber et al, 2016; Bonenberger et al, 2015; Chou et al, 2006b; Lopez Soto and Catanesi, 2015; Sia et al, 2008). In addition, the G allele is associated with enhanced rewarding effects of alcohol and nicotine and marked deficits in fronto-striatal inhibitory control (Bach et al, 2015; Courtney et al, 2013; Ray et al, 2006), indicating that this SNP may be associated with vulnerability to substance abuse.…”